Bacterial Infection
Conditions
Keywords
Double-blind, Intravenous Ertapenem, Phase 1, Safety, Zidebactam (WCK 6777)
Brief summary
This is a Phase 1, single center study to investigate the safety, tolerability, and pharmacokinetics (PK) of three dose-level groups of WCK 6777 (ERT and ZID combination), and two dose-level groups of ERT alone and ZID (WCK 5107) alone in 52 healthy adult male and female subjects aged 18 to 45 years old (both inclusive). Seven treatment cohorts will be evaluated in this study. WCK 6777 will be evaluated in three cohorts - Cohorts 1, 4 and 7- of 8 subjects each (6 study drug combinations and 2 placebos); ERT will be evaluated alone in two cohorts - Cohorts 2 and 5- of 8 subject each (6 ERT and 2 placebos); and ZID will be evaluated in two cohorts, Cohorts 3 and 6, of 6 subjects each (all ZID). The study will be placebo-controlled and double-blinded in all cohorts except Cohorts 3 and 6. No placebo subjects are included in standalone ZID cohorts, since adequate safety data for higher doses of ZID alone in comparison with placebo are available from completed Phase 1 studies of WCK 5107 (ZID) alone and the ZID-only arms of WCK 5222 (cefepime + ZID) studies. The primary objective is to assess the safety and tolerability of three dose-escalating regimens of WCK 6777 ( ERT and ZID combination) and two-dose escalating regimens of standalone ERT or ZID following single daily doses for 7 days in healthy adult subjects.
Detailed description
This is a Phase 1, single center study to investigate the safety, tolerability, and pharmacokinetics (PK) of three dose-level groups of WCK 6777 (ERT and ZID combination), and two dose-level groups of ERT alone and ZID (WCK 5107) alone in 52 healthy adult male and female subjects aged 18 to 45 years old (both inclusive). Seven treatment cohorts will be evaluated in this study. WCK 6777 will be evaluated in three cohorts - Cohorts 1, 4 and 7- of 8 subjects each (6 study drug combinations and 2 placebos); ERT will be evaluated alone in two cohorts - Cohorts 2 and 5- of 8 subject each (6 ERT and 2 placebos); and ZID will be evaluated in two cohorts, Cohorts 3 and 6, of 6 subjects each (all ZID). The study will be placebo-controlled and double-blinded in all cohorts except Cohorts 3 and 6. No placebo subjects are included in standalone ZID cohorts, since adequate safety data for higher doses of ZID alone in comparison with placebo are available from completed Phase 1 studies of WCK 5107 (ZID) alone and the ZID-only arms of WCK 5222 (cefepime + ZID) studies. In each cohort, either study drugs alone or their combination will be administered by a single intravenous infusion (IV) of 100 mL daily for 7 consecutive days in Cohort 1 or 250 mL daily for 7 consecutive days in Cohorts 2 to 7. For each treatment cohort, however, the dose will be progressively escalated from 1 g/daily to 2 g/daily and to 3 g/daily, and the duration of infusion time increased from 30 min to 1 h and to 2 h over the course of the study. In Cohort 1, WCK 6777 2 g (ERT 1 g/daily combined with ZID 1 g/daily) will be administered in 30 (±5) minutes (min); in Cohort 2 (ERT 2 g/daily), Cohort 3 (ZID 2 g/daily), and Cohort 4 (WCK 6777 4 g \[ERT 2 g/daily combined with ZID 2 g/daily\]) the study drug(s) will be administered in 60 (±10) min, and in Cohort 5 (ERT 3 g/daily), Cohort 6 (ZID 3 g daily) and Cohort 7 (WCK 6777 6 g \[ERT 3 g/daily combined with ZID 3 g/daily\]), the study drug(s) will be administered in 120 (±10) min. The primary objective is to assess the safety and tolerability of three dose-escalating regimens of WCK 6777 ( ERT and ZID combination) and two-dose escalating regimens of standalone ERT or ZID following single daily doses for 7 days in healthy adult subjects. The secondary objective is to characterize the PK profiles in plasma (total & free) and in urine of three dose-escalating regimens of WCK 6777 (ERT and ZID combination) and two dose-escalating regimens of standalone ERT or ZID following a single initial dose on Day 1 and after single daily doses for 7 days in healthy adult subjects.
Interventions
DRUGErtapenem
A 1-beta methyl-carbapenem that is structurally related to beta-lactam antibiotics
OTHERPlacebo
Placebo
DRUGWCK 6777
A combination of ertapenem (ERT) and zidebactam (ZID)
DRUGZidebactam
A betaß-lactamase inhibitor and betaß-lactam enhancer from the diazabicyclooctane (DBO) class
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
All investigative site personnel, study volunteers, DMID, Wockhardt and DVC personnel will remain blinded through database lock, with the exception of an unblinded pharmacist/verifier at the research site, an unblinded SDCC biostatistician, and a DMID/CMS manager responsible for PK sample storage.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provide a signed and dated written informed consent and agrees to comply with the study procedures and length of confinement to the research site. 2. Be able to understand and willing to comply with study procedures, restrictions, and requirements, as determined by the Site Principal Investigator (PI) or authorized clinician(s) (listed on FDA Form 1572). 3. Adults 18 to 45 years of age inclusive, including non-pregnant, non-lactating females. 4. Have suitable veins for cannulation or repeated venipuncture. 5. Be in good general health at the time of enrollment. Note 1: Determined by medical history (MH), medication use, physical examination (PE), vital signs (VS), clinical laboratory tests including estimated creatinine clearance (CLCR) \> / = 80 mL/min by the Cockcroft-Gault method, and 12-lead Electrocardiogram (ECG) within reference ranges at Screening and Day-1. Note 2: Exceptions to Blood Pressure (BP), Heart Rate (HR) and laboratory test values being with normal ranges are: * Subjects with baseline HR \> / = 45 to 50 Beats per Minute (bpm) may be accepted if otherwise healthy adults with known history of asymptomatic bradycardia. * Subjects with baseline Systolic Blood Pressure (SBP) up to 140 Millimeters of Mercury (mmHg) and Diastolic Blood Pressure (DBP) up to 90 mmHg may be accepted if otherwise healthy. * A laboratory value that is Grade 1 will be allowed if not considered to be clinically significant by the investigator, with the exception of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), total and direct bilirubin, Blood Urea Nitrogen (BUN), serum creatinine, Creatinine Clearance (CLcr), and urine protein. 6. Sexually active females must be of non-childbearing potential or must use a highly effective method of birth control from screening to 30 days following the last dose of study product. Note 1: A female is considered of childbearing potential unless post-menopausal (defined as history of \> / = 1 year of spontaneous amenorrhea and a Follicle-Stimulating Hormone (FSH) level \>40 IU/L), or permanently surgically sterilized. Note 2: Highly effective contraceptive methods include: (a) surgical sterilization methods, such as tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful tubal obliteration (e.g., Essure(R)) with documented radiological confirmation test at least 90 days after the procedure, or (b) long-acting reversible contraception, such as progestin-releasing subdermal implants, copper intrauterine devices (IUDs), levonorgestrel-releasing IUDs. Note 3: A subject who is not sexually active and abstains from sexual intercourse can be enrolled and abstinence documented. 7. Sexually active males must be vasectomized or agree to use barrier contraception and not donate sperm from first dose of study product until 30 days following the last dose. Note 1: Barrier contraception includes use of condom with spermicide. Note 2: A subject who is not sexually active and abstains from sexual intercourse can be enrolled and abstinence documented. 8. Subjects must be willing to avoid excessive physical exercise within 48 h prior to dosing until discharge from the CTU on Day 8, and 24 h before the last visit (Day 11 +3 days). 9. No history of acute febrile or infectious illness for at least 7 days prior to the administration of study drug(s).
Exclusion criteria
1. Known history of a clinically significant food or drug allergy/hypersensitivity including known allergy/hypersensitivity to Ertapenem (ERT), any ß-lactam drugs or other related drugs. 2. Current seasonal allergies with ongoing symptoms for more than a week prior to dosing requiring glucocorticoids and/or frequent use of antihistamines for treatment. 3. Any history of a chronic condition including renal failure that may increase risk to subject or interfere with endpoint assessment, or any unstable chronic disease. Note 1: Unstable chronic disease is defined by need for frequent medical interventions that lead to a change in medications and/or required hospitalization, surgery or an invasive procedure or emergency department/urgent care visit, as determined by the Site PI. Note 2: Any chronic disease, that has been diagnosed within 90 days of screening is excluded. 4. History of any psychiatric condition that has required hospitalization in the last 12 months or subject is considered psychologically unstable by the investigator. 5. History of any clinically significant (CS) disease or disorder, medical/surgical procedure, or trauma within 4 weeks prior to initiation of administration of study product(s). 6. History of Clostridium difficile induced diarrhea within 1 year before screening 7. Known history of past or current epilepsy or seizure disorders, excluding febrile seizures of childhood. 8. Prior exposure to Zidebactam (ZID). 9. Use of any prohibited prescription or non-prescription medication within 14 days prior to the first dose of study drug(s) as described in Section 6.6 10. Use of any investigational drug product within 30 days or 5 half-lives (whichever is longer) before investigational product administration in this study. 11. Planned participation in a clinical research study that requires treatment with a study drug, blood draws or other invasive assessments during the study period (screening until final visit). 12. Blood or plasma donation of 500 mL within 3 months or more than 100 mL within 30 days before signing informed consent or planned donation prior to completion of this trial. 13. Positive serum pregnancy test for women at screening and urine pregnancy test at check-in. 14. Positive urine alcohol test or urine drug screen test at screening or check-in (Day -1). 15. Positive test for HIV antibodies, hepatitis B-virus surface antigen (HBsAg), or anti-hepatitis C-virus antibodies (anti-HCV) at screening. 16. History of \> / = 10 pack-years smoking in the 5-year period before screening, or positive urine cotinine screen at check-in. Note 1: Nicotine products include cigarettes, e-cigarettes, pipe, cigar, chewing tobacco, nicotine patch. Note 2: Positive urine cotinine at screening is allowed if negative at check-in (Day -1). 17. History of binge drinking or heavy drinking of alcohol at any time in the 6 months before study product administration. Note 1: Binge drinking is defined as 5 or more drinks during single occasion if male, or 4 or more if female. Note 2: Heavy drinking of alcohol is defined as consumption of more than 15 units of alcohol per week if male, or more than 8 units if female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | Day 1 through Day 11 | Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). Number of participants with a TEAE are summarized by dose group and by MedDRA System Organ Class (SOC). |
| Number of Treatment-Emergent Adverse Events Reported | Day 1 through Day 11 | Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). Number of TEAEs reported are summarized by dose group and MedDRA System Organ Class (SOC).. |
| Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Day 1 through Day 11 | Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). TEAEs are assessed by the investigator to determine relationship to the study drug. Number of participants with a related TEAE are summarized by dose group and by MedDRA System Organ Class (SOC). |
| Number of Serious Adverse Events Reported | Day 1 through Day 11 | Serious AEs (SAEs) meet one or more of the following criteria: death, life-threatening AEs, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, substantial disruption of the ability to conduct normal life function, congenital anomaly/birth defect, or important medical events that may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. SAEs are listed. |
| Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Day 1 through Day 11 | Parameters and thresholds include alanine aminotransferase =33 (female (F) 19Y), =30 (F \>19) or =47 U/L (male (M) =19Y); albumin =3.5 g/dL; alkaline phosphatase =129 (F 19Y), =126 (F =49Y), =170 (M 19Y) or =131 U/L (M =49Y); aspartate aminotransferase =33 (19Y) or =41 U/L (20-49Y); bilirubin =1.2 (19Y) or =1.3 mg/dL (\>19Y); calcium =8.8 (4-19Y), =8.5 (20-49Y), =10.5 (4-19Y), =10.3 (F 20-49Y) or =10.4 mg/dL (M 20-49Y); carbon dioxide =19 or =33 mmol/L; creatinine =0.97 (F 18-29Y), =0.98 (F 30-39Y), =1.00 (F 40-49Y), =1.25 (M 18-29Y), =1.27 (M 30-39Y) or =1.30 mg/dL (M 40-49Y); direct bilirubin =0.3 mg/dL; glucose =64 or =100 mg/dL; potassium =3.7 (19Y), =3.4 (\>19Y), = 5.2 (19Y) or = 5.4 mmol/L (\>19Y); protein =6.2 (19Y) or =6.0 g/dL (\>19Y); sodium =134 or =147 mmol/L; and urea nitrogen =21 (19Y) or =26 mg/dL (\>19Y). All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity. |
| Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Day 1 through Day 11 | Parameters and thresholds include basophils =201 x106/L (\>6Y); eosinophils =501 x106/L (\>6Y); hemoglobin =11.4 (female (F) 18Y), =11.6 (F \>18Y), =11.9 (male (M) 18Y) or =13.1 g/dL (M \>18Y); leukocytes =4.4 (18Y), =3.7 (\>18Y), =13.1 (18Y) or =10.9 x109/L (\>18Y); lymphocytes =1199 (18Y) or =849 x106/L (\>18Y); monocytes =901 (18Y) or =951 x106/L (\>18Y); neutrophils =1799 (18Y) or =1499 x106/L (\>18Y); and platelets \<140 x109/L. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity. |
| Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Day 1 through Day 11 | Parameters and thresholds include activated partial thromboplastin time \>32 s, prothrombin intl. normalized ratio \>1.1 (ratio), and prothrombin time \>11.5 s. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity. |
| Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Day 1 through Day 11 | Parameters and thresholds include dipstick measurements of glucose =1+, leukocyte esterase =1+, occult blood =1+, protein =1+ and urinalysis with microscopy results of at least a few bacteria, red blood cells (RBC) =3 per high-powered field (HPF), and white blood cells (WBC) =6 per HPF. If dipstick results were abnormal, urinalysis with microscopy was performed. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | Day 8 and Day 11 | The only ECG parameters graded were PR interval with a threshold of =211 msec and QTcF interval with a threshold of =471 msec (female) or =451 msec (male) or an increase of =30 msec above baseline. ECG values after dosing were considered as TEAEs if they met toxicity grading criteria. |
| Number of Participants With Abnormal Vital Signs (VS) | Day 1 through Day 11 | VS parameters and thresholds include diastolic blood pressure =90 mmHg, oral temperature =37.3 °C, pulse =49 or =101 beats/min, respiratory rate =21 breaths/min, and systolic blood pressure =88 or =131 mmHg. VS could be repeated up to twice more at rest and within at least 5 minutes of each other. The following rules were used to determine which vital sign measurement to use for analysis if repeat measurements occurred: 1. If the first replicate was normal, it was used. 2. If the first and second replicates were both abnormal, the replicate with the higher severity was used. 3. If the first replicate was abnormal, the second replicate was normal, and the third replicate was not performed, the first replicate was used. 4. If the first replicate was abnormal and the second and third replicates were normal, the second replicate was used. 5. If the first and third replicates were abnormal and the second replicate was normal, the abnormal replicate with the higher severity was used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion), AUC(0-tau) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration |
| Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion), AUC(0-tau)/Dose ((µg\*h/mL)/mg), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the terminal elimination half-life, t1/2 (h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the total clearance, CLT (L/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the first-order terminal phase elimination rate constant, Ke (1/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the apparent volume of distribution, Vd (L), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmax,ss (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. These estimates assume steady state has been achieved. |
| Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmin,ss (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. These estimates assume steady state has been achieved. |
| Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized Cmax,ss ((µg/mL)/mg) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. This estimate assumes steady state has been achieved. |
| Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the average concentration over the Dose 7 dosing interval, Cavg (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). Cavg is calculated as AUC(0-tau,ss)/tau. These estimates assume steady state has been achieved. |
| Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the predicted concentration at the end of the dosing interval at steady state, Ctau,ss (µg/mL), parameters estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). These estimates assume steady state has been achieved. |
| Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Median and minimum/maximum of the Tmax,ss (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. The estimate for Tmax,ss assumes steady state has been achieved. |
| Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Median and minimum/maximum of the Tmin (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. |
| Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the area under the concentration-time curve from dosing (time 0 h) extrapolated to 24 h after dosing at steady state, AUC(0-24),ss (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved. |
| Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion) at steady state, AUC(0-tau),ss (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved. |
| Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion) at steady state, AUC(0-tau),ss/Dose ((µg\*h/mL)/mg), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved. |
| Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the terminal elimination half-life, t1/2 (h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the total clearance, CLT (L/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the apparent volume of distribution at steady state, Vd,ss (L), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved. |
| Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusions | Geometric mean (GM), and coefficient of variation percentage (CV%) of the linearity index (ratio) for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. The linearity index is a measure of how linear the relationship is between increase in administered dose and increase in exposure. The linearity index is estimated as AUC(0-tau),ss (Dose 7)/AUC(0-inf) (Dose 1), where the areas under the concentration-time curves from Dose 7 to the end of the dosing interval at steady state and from Dose 1 taken to the limit as the end time becomes arbitrarily large, AUC(0-tau),ss and AUC(0-inf) respectively, are calculated using Phoenix WinNonlin Non-compartmental Analysis with Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). The AUC(0-tau),ss estimate assumes steady state was reached. |
| The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusions | Geometric mean (GM), and coefficient of variation percentage (CV%) of the accumulation ratio of the AUC, RAUC (ratio), parameter for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. RAUC is estimated as AUC(0-tau),ss (Dose 7)/AUC(0-24) (Dose 1), where the areas under the concentration-time curves from Dose 7 to the end of the dosing interval at steady state and from Dose 1 extrapolated to 24 h after Dose 1, AUC(0-tau),ss and AUC(0-24) respectively, are calculated using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). The AUC(0-tau),ss estimate assumes steady state was reached. |
| The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusions | Geometric mean (GM), and coefficient of variation percentage (CV%) of the accumulation ratio of the Cmax, RCmax (ratio), parameter for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. RCmax is estimated as Cmax (Dose 7)/Cmax (Dose 1), where the Cmax parameters are estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h periods following Dose 1 and Dose 7, respectively. |
| Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmax (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group. |
| Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusion | Mean and minimum/maximum of the cumulative amount of unchanged ERT and the cumulative amount of unchanged ZID excreted in urine from zero (predose) to 24 h following Dose 1, Ae,urine(0-24) (mg), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 (Day 1) infusion | Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine, fe,urine (%), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 1 by dose group. These fe,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusion | Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine from zero (predose) to 24 h following Dose 1, fe,urine(0-24) (%), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of renal clearance of ERT and ZID from dosing until the last collected concentration for Dose 1 (24 h postdose), CLR(0-24) (mL/h ), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 (Day 7) infusion | Mean and minimum/maximum of the amount of unchanged ERT and the amount of unchanged ZID excreted in urine, Ae,urine (mg), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 7 by dose group. Ae,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusion | Mean and minimum/maximum of the cumulative amount of unchanged ERT and the cumulative amount of unchanged ZID excreted in urine from zero (predose) to 24 h following Dose 7, Ae,urine(0-24) (mg), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 (Day 7) infusion | Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine, fe,urine (%), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 7 by dose group. These fe,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusion | Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine from zero (predose) to 24 h following Dose 7, fe,urine(0-24) (%), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of renal clearance of ERT and ZID from dosing until the last collected concentration for Dose 7 (24 h postdose), CLR(0-24) (mL/h), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 (Day 1) infusion | Mean and minimum/maximum of the amount of unchanged ERT and the amount of unchanged ZID excreted in urine, Ae,urine (mg), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 1 by dose group. Ae,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above. |
| Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmin (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group. |
| Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the Ctau (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group. Ctau is estimated using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized Cmax ((µg/mL)/mg) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group |
| Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Median and minimum/maximum of the Tmax (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group. |
| Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Median and minimum/maximum of the Tmin (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group. |
| Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) extrapolated to the time the concentration is predicted to reach the lower limit of quantification (LLOQ), AUC(0-t) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) to the time of last measured concentration, AUC(0-last) (µg\*h/mL),parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group. |
| Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) taken to the limit as the end time becomes arbitrarily large, AUC(0-inf) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
| Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion | Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) extrapolated to 24 h after dosing, AUC(0-24) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited between 19APR2023 and 24OCT2023 by the clinical trials unit (CTU) utilizing the CTU subject database and IRB-approved advertisements and social media.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - WCK 6777 2 g WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID) | 6 |
| Cohort 2 - ERT 2 g Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics | 6 |
| Cohort 3 - ZID 2 g Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class | 6 |
| Cohort 4 - WCK 6777 4 g WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID) | 6 |
| Cohort 5 - ERT 3 g Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics | 7 |
| Cohort 6 - ZID 3 g Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class | 7 |
| Cohort 7 - WCK 6777 6 g WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID) | 6 |
| Placebo Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort. | 10 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Enrolled but treatment not administered | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 - WCK 6777 2 g | Cohort 2 - ERT 2 g | Cohort 3 - ZID 2 g | Cohort 4 - WCK 6777 4 g | Cohort 5 - ERT 3 g | Cohort 6 - ZID 3 g | Cohort 7 - WCK 6777 6 g | Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.7 years STANDARD_DEVIATION 7.3 | 35.2 years STANDARD_DEVIATION 9.2 | 32.3 years STANDARD_DEVIATION 9.5 | 33.2 years STANDARD_DEVIATION 7 | 33.6 years STANDARD_DEVIATION 7.9 | 37.3 years STANDARD_DEVIATION 5.6 | 29.2 years STANDARD_DEVIATION 9 | 30.7 years STANDARD_DEVIATION 6.7 | 33.0 years STANDARD_DEVIATION 7.6 |
| BMI | 27.08 kg/m2 STANDARD_DEVIATION 2.93 | 28.57 kg/m2 STANDARD_DEVIATION 2.05 | 25.18 kg/m2 STANDARD_DEVIATION 3.38 | 27.63 kg/m2 STANDARD_DEVIATION 2.85 | 23.83 kg/m2 STANDARD_DEVIATION 1.62 | 27.27 kg/m2 STANDARD_DEVIATION 2.76 | 24.05 kg/m2 STANDARD_DEVIATION 4.36 | 26.87 kg/m2 STANDARD_DEVIATION 2.82 | 26.32 kg/m2 STANDARD_DEVIATION 3.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 5 Participants | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 6 Participants | 9 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants | 7 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 2 Participants | 4 Participants | 5 Participants | 4 Participants | 5 Participants | 1 Participants | 2 Participants | 23 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 5 Participants | 4 Participants | 6 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 5 / 6 | 5 / 6 | 4 / 6 | 2 / 6 | 4 / 6 | 9 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 |
Outcome results
Primary
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Parameters and thresholds include alanine aminotransferase =33 (female (F) 19Y), =30 (F \>19) or =47 U/L (male (M) =19Y); albumin =3.5 g/dL; alkaline phosphatase =129 (F 19Y), =126 (F =49Y), =170 (M 19Y) or =131 U/L (M =49Y); aspartate aminotransferase =33 (19Y) or =41 U/L (20-49Y); bilirubin =1.2 (19Y) or =1.3 mg/dL (\>19Y); calcium =8.8 (4-19Y), =8.5 (20-49Y), =10.5 (4-19Y), =10.3 (F 20-49Y) or =10.4 mg/dL (M 20-49Y); carbon dioxide =19 or =33 mmol/L; creatinine =0.97 (F 18-29Y), =0.98 (F 30-39Y), =1.00 (F 40-49Y), =1.25 (M 18-29Y), =1.27 (M 30-39Y) or =1.30 mg/dL (M 40-49Y); direct bilirubin =0.3 mg/dL; glucose =64 or =100 mg/dL; potassium =3.7 (19Y), =3.4 (\>19Y), = 5.2 (19Y) or = 5.4 mmol/L (\>19Y); protein =6.2 (19Y) or =6.0 g/dL (\>19Y); sodium =134 or =147 mmol/L; and urea nitrogen =21 (19Y) or =26 mg/dL (\>19Y). All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity.
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose decrease | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Creatinine increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Aspartate aminotransferase increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium decrease | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alkaline phosphatase increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alanine aminotransferase increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium decrease | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Direct bilirubin increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Albumin decrease | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide decrease | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Protein decrease | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Bilirubin increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium decrease | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Urea nitrogen increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Bilirubin increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Aspartate aminotransferase increase | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alkaline phosphatase increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Albumin decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alanine aminotransferase increase | 2 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Urea nitrogen increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Creatinine increase | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Direct bilirubin increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Protein decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Aspartate aminotransferase increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Direct bilirubin increase | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Albumin decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Bilirubin increase | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alanine aminotransferase increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Urea nitrogen increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Protein decrease | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alkaline phosphatase increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Creatinine increase | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Creatinine increase | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium decrease | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium decrease | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide decrease | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Direct bilirubin increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose decrease | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose increase | 2 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium decrease | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Protein decrease | 2 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Urea nitrogen increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alanine aminotransferase increase | 2 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alkaline phosphatase increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Aspartate aminotransferase increase | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Albumin decrease | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Bilirubin increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Aspartate aminotransferase increase | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Protein decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium decrease | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Creatinine increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Urea nitrogen increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Albumin decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Bilirubin increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alkaline phosphatase increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Direct bilirubin increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alanine aminotransferase increase | 2 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Aspartate aminotransferase increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Bilirubin increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Urea nitrogen increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium decrease | 1 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Creatinine increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Protein decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide increase | 1 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alanine aminotransferase increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Albumin decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alkaline phosphatase increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Direct bilirubin increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Protein decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Aspartate aminotransferase increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Direct bilirubin increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alanine aminotransferase increase | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Albumin decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide increase | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Bilirubin increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Creatinine increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Urea nitrogen increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alkaline phosphatase increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alanine aminotransferase increase | 1 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Direct bilirubin increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Creatinine increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Protein decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium decrease | 1 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Sodium increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Urea nitrogen increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Albumin decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Alkaline phosphatase increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Carbon dioxide decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Calcium decrease | 1 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Aspartate aminotransferase increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Bilirubin increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Glucose increase | 1 Participants |
| Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results | Potassium decrease | 0 Participants |
Primary
Number of Participants With Abnormal Coagulation Laboratory Toxicity Results
Parameters and thresholds include activated partial thromboplastin time \>32 s, prothrombin intl. normalized ratio \>1.1 (ratio), and prothrombin time \>11.5 s. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity.
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Activated partial thromboplastin time increase | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin time increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin intl. normalized ratio (INR) increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin time increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin intl. normalized ratio (INR) increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Activated partial thromboplastin time increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin time increase | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Activated partial thromboplastin time increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin intl. normalized ratio (INR) increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Activated partial thromboplastin time increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin intl. normalized ratio (INR) increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin time increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin intl. normalized ratio (INR) increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Activated partial thromboplastin time increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin time increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin intl. normalized ratio (INR) increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Activated partial thromboplastin time increase | 1 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin time increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin intl. normalized ratio (INR) increase | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Activated partial thromboplastin time increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin time increase | 1 Participants |
| Placebo | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Activated partial thromboplastin time increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin intl. normalized ratio (INR) increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results | Prothrombin time increase | 1 Participants |
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results
The only ECG parameters graded were PR interval with a threshold of =211 msec and QTcF interval with a threshold of =471 msec (female) or =451 msec (male) or an increase of =30 msec above baseline. ECG values after dosing were considered as TEAEs if they met toxicity grading criteria.
Time frame: Day 8 and Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | QTcF interval | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | PR interval | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | QTcF interval | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | PR interval | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | QTcF interval | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | PR interval | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | PR interval | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | QTcF interval | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | PR interval | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | QTcF interval | 1 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | PR interval | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | QTcF interval | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | PR interval | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | QTcF interval | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | PR interval | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results | QTcF interval | 0 Participants |
Primary
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Parameters and thresholds include basophils =201 x106/L (\>6Y); eosinophils =501 x106/L (\>6Y); hemoglobin =11.4 (female (F) 18Y), =11.6 (F \>18Y), =11.9 (male (M) 18Y) or =13.1 g/dL (M \>18Y); leukocytes =4.4 (18Y), =3.7 (\>18Y), =13.1 (18Y) or =10.9 x109/L (\>18Y); lymphocytes =1199 (18Y) or =849 x106/L (\>18Y); monocytes =901 (18Y) or =951 x106/L (\>18Y); neutrophils =1799 (18Y) or =1499 x106/L (\>18Y); and platelets \<140 x109/L. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity.
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Basophils increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes decrease | 3 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Eosinophils increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Hemoglobin decrease | 3 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Neutrophils decrease | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Platelets decrease | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Monocytes increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Lymphocytes decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Platelets decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Monocytes increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Basophils increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Neutrophils decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Eosinophils increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Lymphocytes decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Hemoglobin decrease | 2 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Lymphocytes decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Platelets decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Neutrophils decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Hemoglobin decrease | 2 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Basophils increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Monocytes increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Eosinophils increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Lymphocytes decrease | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Neutrophils decrease | 2 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Basophils increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Platelets decrease | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Eosinophils increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Monocytes increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Hemoglobin decrease | 2 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes decrease | 2 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Neutrophils decrease | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Basophils increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Eosinophils increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Hemoglobin decrease | 2 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes decrease | 2 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Lymphocytes decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Monocytes increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Platelets decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Platelets decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Monocytes increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Neutrophils decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Basophils increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Lymphocytes decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Hemoglobin decrease | 2 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Eosinophils increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes decrease | 3 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Lymphocytes decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Hemoglobin decrease | 2 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Platelets decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Monocytes increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Eosinophils increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Neutrophils decrease | 2 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Basophils increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Neutrophils decrease | 2 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Hemoglobin decrease | 5 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Eosinophils increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Basophils increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Platelets decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Lymphocytes decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Monocytes increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results | Leukocytes decrease | 2 Participants |
Primary
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results
Parameters and thresholds include dipstick measurements of glucose =1+, leukocyte esterase =1+, occult blood =1+, protein =1+ and urinalysis with microscopy results of at least a few bacteria, red blood cells (RBC) =3 per high-powered field (HPF), and white blood cells (WBC) =6 per HPF. If dipstick results were abnormal, urinalysis with microscopy was performed. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity.
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | RBC increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | WBC increase | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Occult blood increase | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Leukocyte esterase increase | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Protein increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Bacteria increase | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Bacteria increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | RBC increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Leukocyte esterase increase | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Occult blood increase | 2 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Protein increase | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | WBC increase | 2 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | RBC increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Bacteria increase | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Protein increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Leukocyte esterase increase | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | WBC increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Occult blood increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Protein increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Bacteria increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Leukocyte esterase increase | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | WBC increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Occult blood increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | RBC increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Protein increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Leukocyte esterase increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Occult blood increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | RBC increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | WBC increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Bacteria increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Protein increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Bacteria increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | RBC increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Occult blood increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | WBC increase | 1 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Leukocyte esterase increase | 1 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Leukocyte esterase increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | WBC increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | RBC increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Bacteria increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Occult blood increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Protein increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Bacteria increase | 3 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Protein increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | WBC increase | 1 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Glucose increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Occult blood increase | 1 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | RBC increase | 1 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results | Leukocyte esterase increase | 2 Participants |
Primary
Number of Participants With Abnormal Vital Signs (VS)
VS parameters and thresholds include diastolic blood pressure =90 mmHg, oral temperature =37.3 °C, pulse =49 or =101 beats/min, respiratory rate =21 breaths/min, and systolic blood pressure =88 or =131 mmHg. VS could be repeated up to twice more at rest and within at least 5 minutes of each other. The following rules were used to determine which vital sign measurement to use for analysis if repeat measurements occurred: 1. If the first replicate was normal, it was used. 2. If the first and second replicates were both abnormal, the replicate with the higher severity was used. 3. If the first replicate was abnormal, the second replicate was normal, and the third replicate was not performed, the first replicate was used. 4. If the first replicate was abnormal and the second and third replicates were normal, the second replicate was used. 5. If the first and third replicates were abnormal and the second replicate was normal, the abnormal replicate with the higher severity was used.
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Vital Signs (VS) | Diastolic blood pressure increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure increase | 2 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse increase | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Vital Signs (VS) | Oral temperature increase | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Vital Signs (VS) | Respiratory rate increase | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse decrease | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Vital Signs (VS) | Oral temperature increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse decrease | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Vital Signs (VS) | Diastolic blood pressure increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Vital Signs (VS) | Respiratory rate increase | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure decrease | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Vital Signs (VS) | Diastolic blood pressure increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure increase | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Vital Signs (VS) | Respiratory rate increase | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Abnormal Vital Signs (VS) | Oral temperature increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Vital Signs (VS) | Oral temperature increase | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Vital Signs (VS) | Respiratory rate increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Vital Signs (VS) | Diastolic blood pressure increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse decrease | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse increase | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse decrease | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Vital Signs (VS) | Respiratory rate increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Vital Signs (VS) | Oral temperature increase | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure decrease | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Abnormal Vital Signs (VS) | Diastolic blood pressure increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Vital Signs (VS) | Respiratory rate increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Vital Signs (VS) | Oral temperature increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse increase | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure increase | 1 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure decrease | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Abnormal Vital Signs (VS) | Diastolic blood pressure increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Vital Signs (VS) | Oral temperature increase | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Vital Signs (VS) | Pulse decrease | 2 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Vital Signs (VS) | Diastolic blood pressure increase | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure decrease | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Abnormal Vital Signs (VS) | Respiratory rate increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs (VS) | Diastolic blood pressure increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs (VS) | Pulse increase | 1 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs (VS) | Pulse decrease | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs (VS) | Respiratory rate increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs (VS) | Oral temperature increase | 2 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs (VS) | Systolic blood pressure increase | 1 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events
Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). Number of participants with a TEAE are summarized by dose group and by MedDRA System Organ Class (SOC).
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Investigations | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Blood and lymphatic system disorders | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Injury, poisoning and procedural complications | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Nervous system disorders | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Skin and subcutaneous tissue disorders | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Gastrointestinal disorders | 2 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Renal and urinary disorders | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Musculoskeletal and connective tissue disorders | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | General disorders and administration site conditions | 3 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events | Infections and infestations | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Investigations | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Blood and lymphatic system disorders | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Gastrointestinal disorders | 2 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Nervous system disorders | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Renal and urinary disorders | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Infections and infestations | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events | General disorders and administration site conditions | 5 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Renal and urinary disorders | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Gastrointestinal disorders | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | General disorders and administration site conditions | 5 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Blood and lymphatic system disorders | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Investigations | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Infections and infestations | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Skin and subcutaneous tissue disorders | 3 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events | Nervous system disorders | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Investigations | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Nervous system disorders | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Infections and infestations | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Blood and lymphatic system disorders | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Gastrointestinal disorders | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | General disorders and administration site conditions | 4 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Renal and urinary disorders | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Nervous system disorders | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | General disorders and administration site conditions | 4 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Infections and infestations | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Blood and lymphatic system disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Gastrointestinal disorders | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Renal and urinary disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Investigations | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Infections and infestations | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Blood and lymphatic system disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Gastrointestinal disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | General disorders and administration site conditions | 2 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Investigations | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Musculoskeletal and connective tissue disorders | 1 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Nervous system disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Renal and urinary disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Investigations | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Infections and infestations | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Gastrointestinal disorders | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | General disorders and administration site conditions | 3 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Blood and lymphatic system disorders | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Nervous system disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events | Renal and urinary disorders | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Infections and infestations | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Musculoskeletal and connective tissue disorders | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Investigations | 3 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Injury, poisoning and procedural complications | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Skin and subcutaneous tissue disorders | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Nervous system disorders | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Gastrointestinal disorders | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | General disorders and administration site conditions | 6 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Blood and lymphatic system disorders | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Renal and urinary disorders | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). TEAEs are assessed by the investigator to determine relationship to the study drug. Number of participants with a related TEAE are summarized by dose group and by MedDRA System Organ Class (SOC).
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Investigations | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Infections and infestations | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Nervous system disorders | 1 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Blood and lymphatic system disorders | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | General disorders and administration site conditions | 3 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Renal and urinary disorders | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 1 - WCK 6777 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Gastrointestinal disorders | 2 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Nervous system disorders | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | General disorders and administration site conditions | 5 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Infections and infestations | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Investigations | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Gastrointestinal disorders | 2 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Blood and lymphatic system disorders | 1 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 2 - ERT 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Renal and urinary disorders | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Blood and lymphatic system disorders | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | General disorders and administration site conditions | 4 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Renal and urinary disorders | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Nervous system disorders | 1 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Gastrointestinal disorders | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Infections and infestations | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 3 - ZID 2 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Investigations | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Infections and infestations | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | General disorders and administration site conditions | 3 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Nervous system disorders | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Renal and urinary disorders | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Investigations | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Gastrointestinal disorders | 1 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 4 - WCK 6777 4 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Blood and lymphatic system disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Investigations | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Gastrointestinal disorders | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Nervous system disorders | 1 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Renal and urinary disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Blood and lymphatic system disorders | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | General disorders and administration site conditions | 2 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Infections and infestations | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 5 - ERT 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Nervous system disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Gastrointestinal disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Investigations | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Renal and urinary disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | General disorders and administration site conditions | 2 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Blood and lymphatic system disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 6 - ZID 3 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Infections and infestations | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Nervous system disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Skin and subcutaneous tissue disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Musculoskeletal and connective tissue disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Investigations | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Blood and lymphatic system disorders | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Gastrointestinal disorders | 1 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | General disorders and administration site conditions | 3 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Injury, poisoning and procedural complications | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Infections and infestations | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Renal and urinary disorders | 0 Participants |
| Cohort 7 - WCK 6777 6 g | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Infections and infestations | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Musculoskeletal and connective tissue disorders | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | General disorders and administration site conditions | 4 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Gastrointestinal disorders | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Renal and urinary disorders | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Skin and subcutaneous tissue disorders | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Injury, poisoning and procedural complications | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Nervous system disorders | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Blood and lymphatic system disorders | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events Related to Study Product | Investigations | 2 Participants |
Primary
Number of Serious Adverse Events Reported
Serious AEs (SAEs) meet one or more of the following criteria: death, life-threatening AEs, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, substantial disruption of the ability to conduct normal life function, congenital anomaly/birth defect, or important medical events that may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. SAEs are listed.
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Serious Adverse Events Reported | 0 events |
| Cohort 2 - ERT 2 g | Number of Serious Adverse Events Reported | 0 events |
| Cohort 3 - ZID 2 g | Number of Serious Adverse Events Reported | 0 events |
| Cohort 4 - WCK 6777 4 g | Number of Serious Adverse Events Reported | 0 events |
| Cohort 5 - ERT 3 g | Number of Serious Adverse Events Reported | 0 events |
| Cohort 6 - ZID 3 g | Number of Serious Adverse Events Reported | 0 events |
| Cohort 7 - WCK 6777 6 g | Number of Serious Adverse Events Reported | 0 events |
| Placebo | Number of Serious Adverse Events Reported | 0 events |
Primary
Number of Treatment-Emergent Adverse Events Reported
Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). Number of TEAEs reported are summarized by dose group and MedDRA System Organ Class (SOC)..
Time frame: Day 1 through Day 11
Population: Safety Population: All participants that received any amount of study drug(s).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Respiratory, thoracic and mediastinal disorders | 0 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Skin and subcutaneous tissue disorders | 1 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Renal and urinary disorders | 0 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Gastrointestinal disorders | 3 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Nervous system disorders | 1 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | General disorders and administration site conditions | 6 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Musculoskeletal and connective tissue disorders | 1 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Blood and lymphatic system disorders | 0 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Infections and infestations | 0 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Investigations | 1 events |
| Cohort 1 - WCK 6777 2 g | Number of Treatment-Emergent Adverse Events Reported | Injury, poisoning and procedural complications | 1 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Renal and urinary disorders | 1 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Musculoskeletal and connective tissue disorders | 0 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Blood and lymphatic system disorders | 1 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | General disorders and administration site conditions | 11 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Skin and subcutaneous tissue disorders | 0 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Investigations | 0 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Gastrointestinal disorders | 2 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Injury, poisoning and procedural complications | 0 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Nervous system disorders | 1 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Infections and infestations | 1 events |
| Cohort 2 - ERT 2 g | Number of Treatment-Emergent Adverse Events Reported | Respiratory, thoracic and mediastinal disorders | 0 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Investigations | 1 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Blood and lymphatic system disorders | 1 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | General disorders and administration site conditions | 8 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Skin and subcutaneous tissue disorders | 3 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Infections and infestations | 0 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Musculoskeletal and connective tissue disorders | 0 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Renal and urinary disorders | 0 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Gastrointestinal disorders | 0 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Respiratory, thoracic and mediastinal disorders | 1 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Nervous system disorders | 1 events |
| Cohort 3 - ZID 2 g | Number of Treatment-Emergent Adverse Events Reported | Injury, poisoning and procedural complications | 0 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Nervous system disorders | 0 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Respiratory, thoracic and mediastinal disorders | 0 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Renal and urinary disorders | 1 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | General disorders and administration site conditions | 6 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Infections and infestations | 0 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Skin and subcutaneous tissue disorders | 0 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Investigations | 1 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Injury, poisoning and procedural complications | 0 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Gastrointestinal disorders | 1 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Musculoskeletal and connective tissue disorders | 0 events |
| Cohort 4 - WCK 6777 4 g | Number of Treatment-Emergent Adverse Events Reported | Blood and lymphatic system disorders | 0 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Investigations | 2 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Blood and lymphatic system disorders | 0 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Gastrointestinal disorders | 1 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | General disorders and administration site conditions | 6 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Infections and infestations | 0 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Injury, poisoning and procedural complications | 0 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Musculoskeletal and connective tissue disorders | 0 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Nervous system disorders | 1 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Renal and urinary disorders | 0 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Respiratory, thoracic and mediastinal disorders | 0 events |
| Cohort 5 - ERT 3 g | Number of Treatment-Emergent Adverse Events Reported | Skin and subcutaneous tissue disorders | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Investigations | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Skin and subcutaneous tissue disorders | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Gastrointestinal disorders | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Nervous system disorders | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Blood and lymphatic system disorders | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Renal and urinary disorders | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Musculoskeletal and connective tissue disorders | 1 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | General disorders and administration site conditions | 3 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Respiratory, thoracic and mediastinal disorders | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Injury, poisoning and procedural complications | 0 events |
| Cohort 6 - ZID 3 g | Number of Treatment-Emergent Adverse Events Reported | Infections and infestations | 0 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Injury, poisoning and procedural complications | 0 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | General disorders and administration site conditions | 6 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Skin and subcutaneous tissue disorders | 0 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Gastrointestinal disorders | 1 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Nervous system disorders | 0 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Infections and infestations | 0 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Blood and lymphatic system disorders | 1 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Investigations | 1 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Musculoskeletal and connective tissue disorders | 0 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Renal and urinary disorders | 0 events |
| Cohort 7 - WCK 6777 6 g | Number of Treatment-Emergent Adverse Events Reported | Respiratory, thoracic and mediastinal disorders | 0 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Renal and urinary disorders | 0 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Nervous system disorders | 2 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Respiratory, thoracic and mediastinal disorders | 0 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Musculoskeletal and connective tissue disorders | 0 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Investigations | 3 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Infections and infestations | 0 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Injury, poisoning and procedural complications | 0 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | General disorders and administration site conditions | 14 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Gastrointestinal disorders | 1 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Blood and lymphatic system disorders | 1 events |
| Placebo | Number of Treatment-Emergent Adverse Events Reported | Skin and subcutaneous tissue disorders | 1 events |
Secondary
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Mean and minimum/maximum of the amount of unchanged ERT and the amount of unchanged ZID excreted in urine, Ae,urine (mg), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 1 by dose group. Ae,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 12-24 h | 49.80 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 4-8 h | 159.23 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 19.93 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 150.55 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 0-4 h | 339.62 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 8-12 h | 64.30 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 544.83 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 33.28 mg |
| Cohort 2 - ERT 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 4-8 h | 275.67 mg |
| Cohort 2 - ERT 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 8-12 h | 122.38 mg |
| Cohort 2 - ERT 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 0-4 h | 748.60 mg |
| Cohort 2 - ERT 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 12-24 h | 84.22 mg |
| Cohort 3 - ZID 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 80.35 mg |
| Cohort 3 - ZID 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 27.02 mg |
| Cohort 3 - ZID 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 360.00 mg |
| Cohort 3 - ZID 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 1336.67 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 12-24 h | 54.38 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 0-4 h | 794.50 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 4-8 h | 202.67 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 8-12 h | 128.93 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 1475.00 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 259.00 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 83.72 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 25.53 mg |
| Cohort 5 - ERT 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 0-4 h | 768.60 mg |
| Cohort 5 - ERT 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 12-24 h | 149.15 mg |
| Cohort 5 - ERT 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 4-8 h | 713.50 mg |
| Cohort 5 - ERT 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 8-12 h | 173.50 mg |
| Cohort 6 - ZID 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 75.35 mg |
| Cohort 6 - ZID 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 631.67 mg |
| Cohort 6 - ZID 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 1838.33 mg |
| Cohort 6 - ZID 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 143.50 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 4-8 h | 605.83 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 1366.50 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 167.67 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 12-24 h | 106.95 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 8-12 h | 192.00 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 1006.00 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 75.83 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT - 0-4 h | 670.13 mg |
Secondary
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Mean and minimum/maximum of the amount of unchanged ERT and the amount of unchanged ZID excreted in urine, Ae,urine (mg), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 7 by dose group. Ae,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 (Day 7) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 43.04 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 357.83 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 624.50 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 27.93 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 113.37 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 14.75 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 110.20 mg |
| Cohort 1 - WCK 6777 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 54.95 mg |
| Cohort 2 - ERT 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 136.54 mg |
| Cohort 2 - ERT 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 344.17 mg |
| Cohort 2 - ERT 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 29.69 mg |
| Cohort 2 - ERT 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 702.30 mg |
| Cohort 3 - ZID 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 302.00 mg |
| Cohort 3 - ZID 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 62.37 mg |
| Cohort 3 - ZID 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 1210.33 mg |
| Cohort 3 - ZID 2 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 45.58 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 88.86 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 777.80 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 234.94 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 65.46 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 1465.00 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 246.00 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 62.98 mg |
| Cohort 4 - WCK 6777 4 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 32.48 mg |
| Cohort 5 - ERT 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 171.80 mg |
| Cohort 5 - ERT 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 1010.40 mg |
| Cohort 5 - ERT 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 603.40 mg |
| Cohort 5 - ERT 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 113.98 mg |
| Cohort 6 - ZID 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 1855.00 mg |
| Cohort 6 - ZID 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 556.83 mg |
| Cohort 6 - ZID 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 67.67 mg |
| Cohort 6 - ZID 3 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 175.00 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 417.33 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 1870.00 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 113.78 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 113.88 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 96.03 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 59.50 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 998.17 mg |
| Cohort 7 - WCK 6777 6 g | Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 654.33 mg |
Secondary
Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the apparent volume of distribution at steady state, Vd,ss (L), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 105.98 liters | Geometric Coefficient of Variation 14 |
| Cohort 1 - WCK 6777 2 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 6.86 liters | Geometric Coefficient of Variation 5 |
| Cohort 1 - WCK 6777 2 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 18.04 liters | Geometric Coefficient of Variation 14 |
| Cohort 1 - WCK 6777 2 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 21.86 liters | Geometric Coefficient of Variation 10 |
| Cohort 2 - ERT 2 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 72.51 liters | Geometric Coefficient of Variation 16 |
| Cohort 2 - ERT 2 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 6.73 liters | Geometric Coefficient of Variation 11 |
| Cohort 3 - ZID 2 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 18.79 liters | Geometric Coefficient of Variation 14 |
| Cohort 3 - ZID 2 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 16.57 liters | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 6.51 liters | Geometric Coefficient of Variation 11 |
| Cohort 4 - WCK 6777 4 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 69.65 liters | Geometric Coefficient of Variation 13 |
| Cohort 4 - WCK 6777 4 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 13.88 liters | Geometric Coefficient of Variation 21 |
| Cohort 4 - WCK 6777 4 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 30.21 liters | Geometric Coefficient of Variation 197 |
| Cohort 5 - ERT 3 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 56.84 liters | Geometric Coefficient of Variation 30 |
| Cohort 5 - ERT 3 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 7.17 liters | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 20.17 liters | Geometric Coefficient of Variation 6 |
| Cohort 6 - ZID 3 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 20.33 liters | Geometric Coefficient of Variation 7 |
| Cohort 7 - WCK 6777 6 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 61.59 liters | Geometric Coefficient of Variation 29 |
| Cohort 7 - WCK 6777 6 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 19.35 liters | Geometric Coefficient of Variation 13 |
| Cohort 7 - WCK 6777 6 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 19.69 liters | Geometric Coefficient of Variation 13 |
| Cohort 7 - WCK 6777 6 g | Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 7.58 liters | Geometric Coefficient of Variation 10 |
Secondary
Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the apparent volume of distribution, Vd (L), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 8.43 liters | Geometric Coefficient of Variation 7 |
| Cohort 1 - WCK 6777 2 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 141.43 liters | Geometric Coefficient of Variation 11 |
| Cohort 1 - WCK 6777 2 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 23.97 liters | Geometric Coefficient of Variation 14 |
| Cohort 1 - WCK 6777 2 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 31.37 liters | Geometric Coefficient of Variation 12 |
| Cohort 2 - ERT 2 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 128.25 liters | Geometric Coefficient of Variation 12 |
| Cohort 2 - ERT 2 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 8.57 liters | Geometric Coefficient of Variation 9 |
| Cohort 3 - ZID 2 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 31.18 liters | Geometric Coefficient of Variation 23 |
| Cohort 3 - ZID 2 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 24.67 liters | Geometric Coefficient of Variation 28 |
| Cohort 4 - WCK 6777 4 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 30.42 liters | Geometric Coefficient of Variation 40 |
| Cohort 4 - WCK 6777 4 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 106.20 liters | Geometric Coefficient of Variation 23 |
| Cohort 4 - WCK 6777 4 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 23.05 liters | Geometric Coefficient of Variation 22 |
| Cohort 4 - WCK 6777 4 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 8.04 liters | Geometric Coefficient of Variation 12 |
| Cohort 5 - ERT 3 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 8.28 liters | Geometric Coefficient of Variation 10 |
| Cohort 5 - ERT 3 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 89.98 liters | Geometric Coefficient of Variation 20 |
| Cohort 6 - ZID 3 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 29.56 liters | Geometric Coefficient of Variation 10 |
| Cohort 6 - ZID 3 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 30.52 liters | Geometric Coefficient of Variation 9 |
| Cohort 7 - WCK 6777 6 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 26.43 liters | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 27.28 liters | Geometric Coefficient of Variation 17 |
| Cohort 7 - WCK 6777 6 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 86.55 liters | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 8.81 liters | Geometric Coefficient of Variation 13 |
Secondary
Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the area under the concentration-time curve from dosing (time 0 h) extrapolated to 24 h after dosing at steady state, AUC(0-24),ss (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 719.86 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 39.48 µg*h/mL | Geometric Coefficient of Variation 6 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 133.35 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 120.70 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1228.88 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 84.22 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 286.34 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 251.56 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1233.66 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 234.14 µg*h/mL | Geometric Coefficient of Variation 30 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 90.51 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 308.35 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 168.05 µg*h/mL | Geometric Coefficient of Variation 23 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1940.84 µg*h/mL | Geometric Coefficient of Variation 6 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 384.53 µg*h/mL | Geometric Coefficient of Variation 7 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 392.09 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 380.11 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1726.43 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 150.93 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 396.60 µg*h/mL | Geometric Coefficient of Variation 14 |
Secondary
Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion) at steady state, AUC(0-tau),ss (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 39.48 µg*h/mL | Geometric Coefficient of Variation 6 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 133.35 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 120.70 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 719.86 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 84.22 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1228.88 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 286.34 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 251.56 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 234.14 µg*h/mL | Geometric Coefficient of Variation 30 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1233.66 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 308.35 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 90.51 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 168.05 µg*h/mL | Geometric Coefficient of Variation 23 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1940.84 µg*h/mL | Geometric Coefficient of Variation 6 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 384.53 µg*h/mL | Geometric Coefficient of Variation 7 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 392.09 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 396.60 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 150.93 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1726.43 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 380.11 µg*h/mL | Geometric Coefficient of Variation 14 |
Secondary
Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) extrapolated to 24 h after dosing, AUC(0-24) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 728.97 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 41.19 µg*h/mL | Geometric Coefficient of Variation 7 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 141.17 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 126.34 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1249.60 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 85.25 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 259.11 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 303.60 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 103.96 µg*h/mL | Geometric Coefficient of Variation 23 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 248.60 µg*h/mL | Geometric Coefficient of Variation 42 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 321.76 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1386.28 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2156.38 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 188.86 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 380.91 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 381.59 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 443.70 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 428.67 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 192.13 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2029.12 µg*h/mL | Geometric Coefficient of Variation 10 |
Secondary
Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) taken to the limit as the end time becomes arbitrarily large, AUC(0-inf) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 742.95 µg*h/mL | Geometric Coefficient of Variation 10 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 41.65 µg*h/mL | Geometric Coefficient of Variation 7 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 141.33 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 126.50 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 85.93 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1265.39 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 259.27 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 303.92 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 249.11 µg*h/mL | Geometric Coefficient of Variation 41 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 104.94 µg*h/mL | Geometric Coefficient of Variation 24 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 322.04 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1404.86 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2199.93 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 190.81 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 381.76 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 381.44 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 444.34 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 429.33 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 193.61 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2065.37 µg*h/mL | Geometric Coefficient of Variation 11 |
Secondary
Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion), AUC(0-tau) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 41.19 µg*h/mL | Geometric Coefficient of Variation 7 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 126.34 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 728.97 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 141.17 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1249.60 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 85.25 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 259.11 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 303.60 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1386.28 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 248.60 µg*h/mL | Geometric Coefficient of Variation 42 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 321.76 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 103.96 µg*h/mL | Geometric Coefficient of Variation 23 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 188.86 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2156.38 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 380.91 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 381.59 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 428.67 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2029.12 µg*h/mL | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 192.13 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 443.70 µg*h/mL | Geometric Coefficient of Variation 14 |
Secondary
Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) extrapolated to the time the concentration is predicted to reach the lower limit of quantification (LLOQ), AUC(0-t) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 723.48 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 39.92 µg*h/mL | Geometric Coefficient of Variation 7 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 140.00 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 125.17 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 83.95 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1241.47 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 257.74 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 302.40 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 247.40 µg*h/mL | Geometric Coefficient of Variation 42 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 102.81 µg*h/mL | Geometric Coefficient of Variation 24 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 320.50 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1377.99 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2148.23 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 187.42 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 379.92 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 379.75 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 442.32 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 427.31 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 190.43 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2024.46 µg*h/mL | Geometric Coefficient of Variation 10 |
Secondary
Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) to the time of last measured concentration, AUC(0-last) (µg\*h/mL),parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 41.04 µg*h/mL | Geometric Coefficient of Variation 7 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 126.34 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 141.17 µg*h/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 728.18 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1247.86 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 2 - ERT 2 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 85.03 µg*h/mL | Geometric Coefficient of Variation 19 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 259.11 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 3 - ZID 2 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 303.42 µg*h/mL | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 103.94 µg*h/mL | Geometric Coefficient of Variation 23 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 321.35 µg*h/mL | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 248.60 µg*h/mL | Geometric Coefficient of Variation 42 |
| Cohort 4 - WCK 6777 4 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1384.69 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2153.20 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 5 - ERT 3 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 188.66 µg*h/mL | Geometric Coefficient of Variation 15 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 381.44 µg*h/mL | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 380.91 µg*h/mL | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 428.67 µg*h/mL | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2027.57 µg*h/mL | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 191.81 µg*h/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 443.70 µg*h/mL | Geometric Coefficient of Variation 14 |
Secondary
Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the average concentration over the Dose 7 dosing interval, Cavg (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). Cavg is calculated as AUC(0-tau,ss)/tau. These estimates assume steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 1.64 µg/mL | Geometric Coefficient of Variation 6 |
| Cohort 1 - WCK 6777 2 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 29.99 µg/mL | Geometric Coefficient of Variation 9 |
| Cohort 1 - WCK 6777 2 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 5.56 µg/mL | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 5.03 µg/mL | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.51 µg/mL | Geometric Coefficient of Variation 18 |
| Cohort 2 - ERT 2 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 51.20 µg/mL | Geometric Coefficient of Variation 13 |
| Cohort 3 - ZID 2 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 11.94 µg/mL | Geometric Coefficient of Variation 20 |
| Cohort 3 - ZID 2 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 10.48 µg/mL | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 51.40 µg/mL | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 9.77 µg/mL | Geometric Coefficient of Variation 30 |
| Cohort 4 - WCK 6777 4 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.77 µg/mL | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 12.83 µg/mL | Geometric Coefficient of Variation 19 |
| Cohort 5 - ERT 3 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 80.91 µg/mL | Geometric Coefficient of Variation 6 |
| Cohort 5 - ERT 3 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 7.01 µg/mL | Geometric Coefficient of Variation 23 |
| Cohort 6 - ZID 3 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 16.32 µg/mL | Geometric Coefficient of Variation 8 |
| Cohort 6 - ZID 3 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 16.05 µg/mL | Geometric Coefficient of Variation 7 |
| Cohort 7 - WCK 6777 6 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 15.83 µg/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 71.98 µg/mL | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 6.29 µg/mL | Geometric Coefficient of Variation 19 |
| Cohort 7 - WCK 6777 6 g | Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 16.52 µg/mL | Geometric Coefficient of Variation 14 |
Secondary
Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24))
Mean and minimum/maximum of the cumulative amount of unchanged ERT and the cumulative amount of unchanged ZID excreted in urine from zero (predose) to 24 h following Dose 1, Ae,urine(0-24) (mg), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ERT | 594.00 mg |
| Cohort 1 - WCK 6777 2 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ZID | 733.17 mg |
| Cohort 2 - ERT 2 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ERT | 1085.67 mg |
| Cohort 3 - ZID 2 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ZID | 1798.33 mg |
| Cohort 4 - WCK 6777 4 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ERT | 1181.83 mg |
| Cohort 4 - WCK 6777 4 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ZID | 1836.67 mg |
| Cohort 5 - ERT 3 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ERT | 1676.67 mg |
| Cohort 6 - ZID 3 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ZID | 2688.33 mg |
| Cohort 7 - WCK 6777 6 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ERT | 1572.17 mg |
| Cohort 7 - WCK 6777 6 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24)) | Unchanged ZID | 2620.00 mg |
Secondary
Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS)
Mean and minimum/maximum of the cumulative amount of unchanged ERT and the cumulative amount of unchanged ZID excreted in urine from zero (predose) to 24 h following Dose 7, Ae,urine(0-24) (mg), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ERT | 552.83 mg |
| Cohort 1 - WCK 6777 2 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ZID | 770.17 mg |
| Cohort 2 - ERT 2 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ERT | 1067.33 mg |
| Cohort 3 - ZID 2 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ZID | 1080.00 mg |
| Cohort 4 - WCK 6777 4 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ERT | 1166 mg |
| Cohort 4 - WCK 6777 4 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ZID | 1808.33 mg |
| Cohort 5 - ERT 3 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ERT | 1898.00 mg |
| Cohort 6 - ZID 3 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ZID | 2656.67 mg |
| Cohort 7 - WCK 6777 6 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ERT | 1624.50 mg |
| Cohort 7 - WCK 6777 6 g | Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS) | Unchanged ZID | 2700.00 mg |
Secondary
Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion) at steady state, AUC(0-tau),ss/Dose ((µg\*h/mL)/mg), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.04 (µg*h/mL)/mg | Geometric Coefficient of Variation 6 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.12 (µg*h/mL)/mg | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.72 (µg*h/mL)/mg | Geometric Coefficient of Variation 9 |
| Cohort 2 - ERT 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.61 (µg*h/mL)/mg | Geometric Coefficient of Variation 13 |
| Cohort 2 - ERT 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.04 (µg*h/mL)/mg | Geometric Coefficient of Variation 18 |
| Cohort 3 - ZID 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.14 (µg*h/mL)/mg | Geometric Coefficient of Variation 20 |
| Cohort 3 - ZID 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.15 (µg*h/mL)/mg | Geometric Coefficient of Variation 19 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.05 (µg*h/mL)/mg | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.62 (µg*h/mL)/mg | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.12 (µg*h/mL)/mg | Geometric Coefficient of Variation 30 |
| Cohort 5 - ERT 3 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.65 (µg*h/mL)/mg | Geometric Coefficient of Variation 6 |
| Cohort 5 - ERT 3 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.06 (µg*h/mL)/mg | Geometric Coefficient of Variation 23 |
| Cohort 6 - ZID 3 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 7 |
| Cohort 6 - ZID 3 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 8 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.58 (µg*h/mL)/mg | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.05 (µg*h/mL)/mg | Geometric Coefficient of Variation 19 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 14 |
Secondary
Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion), AUC(0-tau)/Dose ((µg\*h/mL)/mg), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.73 (µg*h/mL)/mg | Geometric Coefficient of Variation 9 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.04 (µg*h/mL)/mg | Geometric Coefficient of Variation 7 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.14 (µg*h/mL)/mg | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.04 (µg*h/mL)/mg | Geometric Coefficient of Variation 19 |
| Cohort 2 - ERT 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.62 (µg*h/mL)/mg | Geometric Coefficient of Variation 18 |
| Cohort 3 - ZID 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 15 |
| Cohort 3 - ZID 2 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.15 (µg*h/mL)/mg | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.12 (µg*h/mL)/mg | Geometric Coefficient of Variation 41 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.05 (µg*h/mL)/mg | Geometric Coefficient of Variation 24 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.16 (µg*h/mL)/mg | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.69 (µg*h/mL)/mg | Geometric Coefficient of Variation 15 |
| Cohort 5 - ERT 3 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.72 (µg*h/mL)/mg | Geometric Coefficient of Variation 11 |
| Cohort 5 - ERT 3 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.06 (µg*h/mL)/mg | Geometric Coefficient of Variation 15 |
| Cohort 6 - ZID 3 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.13 (µg*h/mL)/mg | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.15 (µg*h/mL)/mg | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.14 (µg*h/mL)/mg | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.06 (µg*h/mL)/mg | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.68 (µg*h/mL)/mg | Geometric Coefficient of Variation 10 |
Secondary
Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized Cmax,ss ((µg/mL)/mg) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. This estimate assumes steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.18 (µg/mL)/mg | Geometric Coefficient of Variation 11 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 24 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.06 (µg/mL)/mg | Geometric Coefficient of Variation 17 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.06 (µg/mL)/mg | Geometric Coefficient of Variation 23 |
| Cohort 2 - ERT 2 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 13 |
| Cohort 2 - ERT 2 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.17 (µg/mL)/mg | Geometric Coefficient of Variation 10 |
| Cohort 3 - ZID 2 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.05 (µg/mL)/mg | Geometric Coefficient of Variation 18 |
| Cohort 3 - ZID 2 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.06 (µg/mL)/mg | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 56 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 23 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.07 (µg/mL)/mg | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.17 (µg/mL)/mg | Geometric Coefficient of Variation 10 |
| Cohort 5 - ERT 3 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.13 (µg/mL)/mg | Geometric Coefficient of Variation 9 |
| Cohort 5 - ERT 3 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 28 |
| Cohort 6 - ZID 3 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 7 |
| Cohort 6 - ZID 3 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 7 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 15 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 28 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.11 (µg/mL)/mg | Geometric Coefficient of Variation 13 |
Secondary
Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized Cmax ((µg/mL)/mg) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 17 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.06 (µg/mL)/mg | Geometric Coefficient of Variation 20 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.07 (µg/mL)/mg | Geometric Coefficient of Variation 15 |
| Cohort 1 - WCK 6777 2 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.20 (µg/mL)/mg | Geometric Coefficient of Variation 14 |
| Cohort 2 - ERT 2 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 17 |
| Cohort 2 - ERT 2 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.15 (µg/mL)/mg | Geometric Coefficient of Variation 9 |
| Cohort 3 - ZID 2 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.05 (µg/mL)/mg | Geometric Coefficient of Variation 16 |
| Cohort 3 - ZID 2 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.06 (µg/mL)/mg | Geometric Coefficient of Variation 22 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.05 (µg/mL)/mg | Geometric Coefficient of Variation 55 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.07 (µg/mL)/mg | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 22 |
| Cohort 4 - WCK 6777 4 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.18 (µg/mL)/mg | Geometric Coefficient of Variation 8 |
| Cohort 5 - ERT 3 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 17 |
| Cohort 5 - ERT 3 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.13 (µg/mL)/mg | Geometric Coefficient of Variation 10 |
| Cohort 6 - ZID 3 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 11 |
| Cohort 6 - ZID 3 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.13 (µg/mL)/mg | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.02 (µg/mL)/mg | Geometric Coefficient of Variation 19 |
| Cohort 7 - WCK 6777 6 g | Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.04 (µg/mL)/mg | Geometric Coefficient of Variation 11 |
Secondary
First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the first-order terminal phase elimination rate constant, Ke (1/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.16 1/h | Geometric Coefficient of Variation 12 |
| Cohort 1 - WCK 6777 2 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.17 1/h | Geometric Coefficient of Variation 11 |
| Cohort 1 - WCK 6777 2 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.30 1/h | Geometric Coefficient of Variation 15 |
| Cohort 1 - WCK 6777 2 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.25 1/h | Geometric Coefficient of Variation 18 |
| Cohort 2 - ERT 2 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.18 1/h | Geometric Coefficient of Variation 21 |
| Cohort 2 - ERT 2 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.18 1/h | Geometric Coefficient of Variation 22 |
| Cohort 3 - ZID 2 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.25 1/h | Geometric Coefficient of Variation 14 |
| Cohort 3 - ZID 2 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.27 1/h | Geometric Coefficient of Variation 14 |
| Cohort 4 - WCK 6777 4 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.26 1/h | Geometric Coefficient of Variation 14 |
| Cohort 4 - WCK 6777 4 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.18 1/h | Geometric Coefficient of Variation 15 |
| Cohort 4 - WCK 6777 4 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.27 1/h | Geometric Coefficient of Variation 12 |
| Cohort 4 - WCK 6777 4 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.18 1/h | Geometric Coefficient of Variation 14 |
| Cohort 5 - ERT 3 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.17 1/h | Geometric Coefficient of Variation 4 |
| Cohort 5 - ERT 3 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.18 1/h | Geometric Coefficient of Variation 12 |
| Cohort 6 - ZID 3 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.27 1/h | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.26 1/h | Geometric Coefficient of Variation 9 |
| Cohort 7 - WCK 6777 6 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.26 1/h | Geometric Coefficient of Variation 6 |
| Cohort 7 - WCK 6777 6 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.26 1/h | Geometric Coefficient of Variation 5 |
| Cohort 7 - WCK 6777 6 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.18 1/h | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.17 1/h | Geometric Coefficient of Variation 10 |
Secondary
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine, fe,urine (%), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 1 by dose group. These fe,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 8-12 h | 6.43 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 12-24 h | 4.98 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 54.48 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 0-4 h | 33.96 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 1.99 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 4-8 h | 15.92 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 3.33 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 15.06 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 0-4 h | 37.46 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 12-24 h | 4.21 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 8-12 h | 6.12 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 4-8 h | 13.78 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 66.70 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 4.02 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 1.35 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 17.98 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 0-4 h | 39.75 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 4.18 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 4-8 h | 10.14 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 8-12 h | 6.45 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 12-24 h | 2.72 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 73.75 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 12.96 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 1.27 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 0-4 h | 25.60 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 4-8 h | 23.77 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 8-12 h | 5.79 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 12-24 h | 4.97 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 21.07 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 2.51 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 61.25 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 4.77 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 12-24 h | 3.57 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 4-8 h | 33.55 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 4-8 h | 20.16 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 8-12 h | 5.60 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 8-12 h | 6.41 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ERT- 0-4 h | 22.33 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 0-4 h | 45.58 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1 | Unchanged ZID - 12-24 h | 2.53 % of dose excreted unchanged |
Secondary
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine, fe,urine (%), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 7 by dose group. These fe,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 (Day 7) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 1.48 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 62.45 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 11.34 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 4.30 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 5.50 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 35.78 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 11.02 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 2.79 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 6.83 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 17.19 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 1.48 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 35.09 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 60.40 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 15.10 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 3.12 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 2.28 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 3.15 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 1.63 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 11.72 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 3.27 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 38.94 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 73.27 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 12.28 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 4.45 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 3.80 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 33.68 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 20.08 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 5.73 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 61.85 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 5.84 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 2.26 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 18.55 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 8-12 h | 3.79 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 4-8 h | 13.91 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 0-4 h | 33.28 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 0-4 h | 62.38 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 12-24 h | 1.98 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ZID - 4-8 h | 21.84 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 12-24 h | 3.20 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7 | Unchanged ERT - 8-12 h | 3.80 % of dose excreted unchanged |
Secondary
Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24))
Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine from zero (predose) to 24 h following Dose 1, fe,urine(0-24) (%), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ZID | 73.32 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ERT | 59.40 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ERT | 54.32 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ZID | 89.82 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ZID | 91.75 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ERT | 58.98 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ERT | 55.85 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ZID | 89.58 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ERT | 52.43 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24)) | Unchanged ZID | 87.32 % of dose excreted unchanged |
Secondary
Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS)
Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine from zero (predose) to 24 h following Dose 7, fe,urine(0-24) (%), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ERT | 55.28 % of dose excreted unchanged |
| Cohort 1 - WCK 6777 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ZID | 77.02 % of dose excreted unchanged |
| Cohort 2 - ERT 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ERT | 53.35 % of dose excreted unchanged |
| Cohort 3 - ZID 2 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ZID | 53.80 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ERT | 58.36 % of dose excreted unchanged |
| Cohort 4 - WCK 6777 4 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ZID | 90.35 % of dose excreted unchanged |
| Cohort 5 - ERT 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ERT | 63.28 % of dose excreted unchanged |
| Cohort 6 - ZID 3 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ZID | 88.48 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ERT | 54.20 % of dose excreted unchanged |
| Cohort 7 - WCK 6777 6 g | Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS) | Unchanged ZID | 89.93 % of dose excreted unchanged |
Secondary
Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the linearity index (ratio) for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. The linearity index is a measure of how linear the relationship is between increase in administered dose and increase in exposure. The linearity index is estimated as AUC(0-tau),ss (Dose 7)/AUC(0-inf) (Dose 1), where the areas under the concentration-time curves from Dose 7 to the end of the dosing interval at steady state and from Dose 1 taken to the limit as the end time becomes arbitrarily large, AUC(0-tau),ss and AUC(0-inf) respectively, are calculated using Phoenix WinNonlin Non-compartmental Analysis with Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). The AUC(0-tau),ss estimate assumes steady state was reached.
Time frame: =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusions
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.95 ratio | Geometric Coefficient of Variation 4 |
| Cohort 1 - WCK 6777 2 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.97 ratio | Geometric Coefficient of Variation 4 |
| Cohort 1 - WCK 6777 2 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.94 ratio | Geometric Coefficient of Variation 4 |
| Cohort 1 - WCK 6777 2 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.95 ratio | Geometric Coefficient of Variation 5 |
| Cohort 2 - ERT 2 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.98 ratio | Geometric Coefficient of Variation 4 |
| Cohort 2 - ERT 2 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.97 ratio | Geometric Coefficient of Variation 7 |
| Cohort 3 - ZID 2 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.94 ratio | Geometric Coefficient of Variation 13 |
| Cohort 3 - ZID 2 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.97 ratio | Geometric Coefficient of Variation 13 |
| Cohort 4 - WCK 6777 4 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.96 ratio | Geometric Coefficient of Variation 5 |
| Cohort 4 - WCK 6777 4 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.86 ratio | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.88 ratio | Geometric Coefficient of Variation 11 |
| Cohort 4 - WCK 6777 4 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.94 ratio | Geometric Coefficient of Variation 26 |
| Cohort 5 - ERT 3 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.89 ratio | Geometric Coefficient of Variation 6 |
| Cohort 5 - ERT 3 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.88 ratio | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 1.01 ratio | Geometric Coefficient of Variation 8 |
| Cohort 6 - ZID 3 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 1.03 ratio | Geometric Coefficient of Variation 7 |
| Cohort 7 - WCK 6777 6 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.89 ratio | Geometric Coefficient of Variation 13 |
| Cohort 7 - WCK 6777 6 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.89 ratio | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.84 ratio | Geometric Coefficient of Variation 9 |
| Cohort 7 - WCK 6777 6 g | Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.78 ratio | Geometric Coefficient of Variation 17 |
Secondary
Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmax,ss (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. These estimates assume steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 181.90 µg/mL | Geometric Coefficient of Variation 11 |
| Cohort 1 - WCK 6777 2 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 15.41 µg/mL | Geometric Coefficient of Variation 24 |
| Cohort 1 - WCK 6777 2 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 63.87 µg/mL | Geometric Coefficient of Variation 17 |
| Cohort 1 - WCK 6777 2 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 57.89 µg/mL | Geometric Coefficient of Variation 23 |
| Cohort 2 - ERT 2 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 38.18 µg/mL | Geometric Coefficient of Variation 13 |
| Cohort 2 - ERT 2 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 341.92 µg/mL | Geometric Coefficient of Variation 10 |
| Cohort 3 - ZID 2 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 103.12 µg/mL | Geometric Coefficient of Variation 18 |
| Cohort 3 - ZID 2 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 115.71 µg/mL | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 83.36 µg/mL | Geometric Coefficient of Variation 57 |
| Cohort 4 - WCK 6777 4 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 36.09 µg/mL | Geometric Coefficient of Variation 23 |
| Cohort 4 - WCK 6777 4 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 130.69 µg/mL | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 344.89 µg/mL | Geometric Coefficient of Variation 10 |
| Cohort 5 - ERT 3 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 387.57 µg/mL | Geometric Coefficient of Variation 9 |
| Cohort 5 - ERT 3 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 57.65 µg/mL | Geometric Coefficient of Variation 28 |
| Cohort 6 - ZID 3 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 109.41 µg/mL | Geometric Coefficient of Variation 7 |
| Cohort 6 - ZID 3 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 111.59 µg/mL | Geometric Coefficient of Variation 7 |
| Cohort 7 - WCK 6777 6 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 113.79 µg/mL | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 111.81 µg/mL | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 50.36 µg/mL | Geometric Coefficient of Variation 28 |
| Cohort 7 - WCK 6777 6 g | Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 343.24 µg/mL | Geometric Coefficient of Variation 13 |
Secondary
Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmax (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 196.66 µg/mL | Geometric Coefficient of Variation 14 |
| Cohort 1 - WCK 6777 2 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 16.60 µg/mL | Geometric Coefficient of Variation 17 |
| Cohort 1 - WCK 6777 2 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 69.67 µg/mL | Geometric Coefficient of Variation 15 |
| Cohort 1 - WCK 6777 2 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 64.35 µg/mL | Geometric Coefficient of Variation 20 |
| Cohort 2 - ERT 2 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 34.00 µg/mL | Geometric Coefficient of Variation 17 |
| Cohort 2 - ERT 2 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 303.43 µg/mL | Geometric Coefficient of Variation 9 |
| Cohort 3 - ZID 2 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 105.42 µg/mL | Geometric Coefficient of Variation 16 |
| Cohort 3 - ZID 2 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 120.41 µg/mL | Geometric Coefficient of Variation 22 |
| Cohort 4 - WCK 6777 4 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 98.41 µg/mL | Geometric Coefficient of Variation 55 |
| Cohort 4 - WCK 6777 4 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 42.10 µg/mL | Geometric Coefficient of Variation 22 |
| Cohort 4 - WCK 6777 4 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 133.51 µg/mL | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 354.41 µg/mL | Geometric Coefficient of Variation 8 |
| Cohort 5 - ERT 3 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 378.71 µg/mL | Geometric Coefficient of Variation 10 |
| Cohort 5 - ERT 3 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 58.45 µg/mL | Geometric Coefficient of Variation 17 |
| Cohort 6 - ZID 3 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 111.71 µg/mL | Geometric Coefficient of Variation 10 |
| Cohort 6 - ZID 3 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 108.79 µg/mL | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 128.42 µg/mL | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 124.99 µg/mL | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 59.42 µg/mL | Geometric Coefficient of Variation 19 |
| Cohort 7 - WCK 6777 6 g | Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 391.87 µg/mL | Geometric Coefficient of Variation 13 |
Secondary
Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmin,ss (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. These estimates assume steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.10 µg/mL | Geometric Coefficient of Variation 28 |
| Cohort 1 - WCK 6777 2 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 µg/mL | Geometric Coefficient of Variation 49 |
| Cohort 1 - WCK 6777 2 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.75 µg/mL | Geometric Coefficient of Variation 30 |
| Cohort 1 - WCK 6777 2 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.12 µg/mL | Geometric Coefficient of Variation 66 |
| Cohort 2 - ERT 2 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.12 µg/mL | Geometric Coefficient of Variation 35 |
| Cohort 2 - ERT 2 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.81 µg/mL | Geometric Coefficient of Variation 114 |
| Cohort 3 - ZID 2 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.10 µg/mL | Geometric Coefficient of Variation 38 |
| Cohort 3 - ZID 2 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.12 µg/mL | Geometric Coefficient of Variation 68 |
| Cohort 4 - WCK 6777 4 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.12 µg/mL | Geometric Coefficient of Variation 60 |
| Cohort 4 - WCK 6777 4 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.17 µg/mL | Geometric Coefficient of Variation 864 |
| Cohort 4 - WCK 6777 4 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.74 µg/mL | Geometric Coefficient of Variation 75 |
| Cohort 4 - WCK 6777 4 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.10 µg/mL | Geometric Coefficient of Variation 46 |
| Cohort 5 - ERT 3 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 4.93 µg/mL | Geometric Coefficient of Variation 2 |
| Cohort 5 - ERT 3 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.23 µg/mL | Geometric Coefficient of Variation 31 |
| Cohort 6 - ZID 3 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 µg/mL | Geometric Coefficient of Variation 27 |
| Cohort 6 - ZID 3 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.14 µg/mL | Geometric Coefficient of Variation 23 |
| Cohort 7 - WCK 6777 6 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.11 µg/mL | Geometric Coefficient of Variation 34 |
| Cohort 7 - WCK 6777 6 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.49 µg/mL | Geometric Coefficient of Variation 65 |
| Cohort 7 - WCK 6777 6 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.12 µg/mL | Geometric Coefficient of Variation 36 |
| Cohort 7 - WCK 6777 6 g | Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.15 µg/mL | Geometric Coefficient of Variation 59 |
Secondary
Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmin (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.15 µg/mL | Geometric Coefficient of Variation 50 |
| Cohort 1 - WCK 6777 2 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.10 µg/mL | Geometric Coefficient of Variation 40 |
| Cohort 1 - WCK 6777 2 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.09 µg/mL | Geometric Coefficient of Variation 37 |
| Cohort 1 - WCK 6777 2 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.09 µg/mL | Geometric Coefficient of Variation 22 |
| Cohort 2 - ERT 2 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.16 µg/mL | Geometric Coefficient of Variation 42 |
| Cohort 2 - ERT 2 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.61 µg/mL | Geometric Coefficient of Variation 107 |
| Cohort 3 - ZID 2 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.07 µg/mL | Geometric Coefficient of Variation 36 |
| Cohort 3 - ZID 2 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.11 µg/mL | Geometric Coefficient of Variation 72 |
| Cohort 4 - WCK 6777 4 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.10 µg/mL | Geometric Coefficient of Variation 39 |
| Cohort 4 - WCK 6777 4 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.14 µg/mL | Geometric Coefficient of Variation 67 |
| Cohort 4 - WCK 6777 4 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.10 µg/mL | Geometric Coefficient of Variation 44 |
| Cohort 4 - WCK 6777 4 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.10 µg/mL | Geometric Coefficient of Variation 60 |
| Cohort 5 - ERT 3 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 7.32 µg/mL | Geometric Coefficient of Variation 14 |
| Cohort 5 - ERT 3 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.36 µg/mL | Geometric Coefficient of Variation 24 |
| Cohort 6 - ZID 3 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 µg/mL | Geometric Coefficient of Variation 28 |
| Cohort 6 - ZID 3 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.14 µg/mL | Geometric Coefficient of Variation 26 |
| Cohort 7 - WCK 6777 6 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.15 µg/mL | Geometric Coefficient of Variation 30 |
| Cohort 7 - WCK 6777 6 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.14 µg/mL | Geometric Coefficient of Variation 34 |
| Cohort 7 - WCK 6777 6 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.28 µg/mL | Geometric Coefficient of Variation 35 |
| Cohort 7 - WCK 6777 6 g | Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 5.91 µg/mL | Geometric Coefficient of Variation 33 |
Secondary
Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the predicted concentration at the end of the dosing interval at steady state, Ctau,ss (µg/mL), parameters estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). These estimates assume steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.75 µg/mL | Geometric Coefficient of Variation 30 |
| Cohort 1 - WCK 6777 2 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.06 µg/mL | Geometric Coefficient of Variation 53 |
| Cohort 1 - WCK 6777 2 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.02 µg/mL | Geometric Coefficient of Variation 68 |
| Cohort 1 - WCK 6777 2 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.06 µg/mL | Geometric Coefficient of Variation 169 |
| Cohort 2 - ERT 2 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.07 µg/mL | Geometric Coefficient of Variation 128 |
| Cohort 2 - ERT 2 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.85 µg/mL | Geometric Coefficient of Variation 111 |
| Cohort 3 - ZID 2 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.07 µg/mL | Geometric Coefficient of Variation 90 |
| Cohort 3 - ZID 2 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.06 µg/mL | Geometric Coefficient of Variation 89 |
| Cohort 4 - WCK 6777 4 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.11 µg/mL | Geometric Coefficient of Variation 2318 |
| Cohort 4 - WCK 6777 4 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.07 µg/mL | Geometric Coefficient of Variation 88 |
| Cohort 4 - WCK 6777 4 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.05 µg/mL | Geometric Coefficient of Variation 176 |
| Cohort 4 - WCK 6777 4 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.74 µg/mL | Geometric Coefficient of Variation 75 |
| Cohort 5 - ERT 3 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 4.93 µg/mL | Geometric Coefficient of Variation 2 |
| Cohort 5 - ERT 3 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.23 µg/mL | Geometric Coefficient of Variation 31 |
| Cohort 6 - ZID 3 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 µg/mL | Geometric Coefficient of Variation 28 |
| Cohort 6 - ZID 3 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.14 µg/mL | Geometric Coefficient of Variation 23 |
| Cohort 7 - WCK 6777 6 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.12 µg/mL | Geometric Coefficient of Variation 35 |
| Cohort 7 - WCK 6777 6 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.11 µg/mL | Geometric Coefficient of Variation 34 |
| Cohort 7 - WCK 6777 6 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.15 µg/mL | Geometric Coefficient of Variation 58 |
| Cohort 7 - WCK 6777 6 g | Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.50 µg/mL | Geometric Coefficient of Variation 64 |
Secondary
Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Ctau (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group. Ctau is estimated using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.08 µg/mL | Geometric Coefficient of Variation 39 |
| Cohort 1 - WCK 6777 2 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.02 µg/mL | Geometric Coefficient of Variation 50 |
| Cohort 1 - WCK 6777 2 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.02 µg/mL | Geometric Coefficient of Variation 101 |
| Cohort 1 - WCK 6777 2 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.04 µg/mL | Geometric Coefficient of Variation 102 |
| Cohort 2 - ERT 2 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.10 µg/mL | Geometric Coefficient of Variation 102 |
| Cohort 2 - ERT 2 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.29 µg/mL | Geometric Coefficient of Variation 112 |
| Cohort 3 - ZID 2 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.06 µg/mL | Geometric Coefficient of Variation 69 |
| Cohort 3 - ZID 2 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.06 µg/mL | Geometric Coefficient of Variation 49 |
| Cohort 4 - WCK 6777 4 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.83 µg/mL | Geometric Coefficient of Variation 61 |
| Cohort 4 - WCK 6777 4 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.05 µg/mL | Geometric Coefficient of Variation 96 |
| Cohort 4 - WCK 6777 4 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.13 µg/mL | Geometric Coefficient of Variation 67 |
| Cohort 4 - WCK 6777 4 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.05 µg/mL | Geometric Coefficient of Variation 87 |
| Cohort 5 - ERT 3 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 6.83 µg/mL | Geometric Coefficient of Variation 16 |
| Cohort 5 - ERT 3 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.31 µg/mL | Geometric Coefficient of Variation 23 |
| Cohort 6 - ZID 3 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.11 µg/mL | Geometric Coefficient of Variation 34 |
| Cohort 6 - ZID 3 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.11 µg/mL | Geometric Coefficient of Variation 33 |
| Cohort 7 - WCK 6777 6 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.12 µg/mL | Geometric Coefficient of Variation 34 |
| Cohort 7 - WCK 6777 6 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 5.44 µg/mL | Geometric Coefficient of Variation 34 |
| Cohort 7 - WCK 6777 6 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.27 µg/mL | Geometric Coefficient of Variation 38 |
| Cohort 7 - WCK 6777 6 g | Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.13 µg/mL | Geometric Coefficient of Variation 31 |
Secondary
Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24))
Geometric mean (GM), and coefficient of variation percentage (CV%) of renal clearance of ERT and ZID from dosing until the last collected concentration for Dose 1 (24 h postdose), CLR(0-24) (mL/h ), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ERT | 0.75 L/h | Geometric Coefficient of Variation 61 |
| Cohort 1 - WCK 6777 2 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ZID | 4.98 L/h | Geometric Coefficient of Variation 39 |
| Cohort 2 - ERT 2 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ERT | 0.78 L/h | Geometric Coefficient of Variation 57 |
| Cohort 3 - ZID 2 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ZID | 5.88 L/h | Geometric Coefficient of Variation 15 |
| Cohort 4 - WCK 6777 4 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ERT | 0.79 L/h | Geometric Coefficient of Variation 41 |
| Cohort 4 - WCK 6777 4 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ZID | 5.63 L/h | Geometric Coefficient of Variation 36 |
| Cohort 5 - ERT 3 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ERT | 0.76 L/h | Geometric Coefficient of Variation 19 |
| Cohort 6 - ZID 3 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ZID | 6.95 L/h | Geometric Coefficient of Variation 25 |
| Cohort 7 - WCK 6777 6 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ERT | 0.73 L/h | Geometric Coefficient of Variation 42 |
| Cohort 7 - WCK 6777 6 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24)) | Unchanged ZID | 5.55 L/h | Geometric Coefficient of Variation 31 |
Secondary
Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS)
Geometric mean (GM), and coefficient of variation percentage (CV%) of renal clearance of ERT and ZID from dosing until the last collected concentration for Dose 7 (24 h postdose), CLR(0-24) (mL/h), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Time frame: 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ERT | 0.74 L/h | Geometric Coefficient of Variation 28 |
| Cohort 1 - WCK 6777 2 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ZID | 5.59 L/h | Geometric Coefficient of Variation 35 |
| Cohort 2 - ERT 2 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ERT | 0.78 L/h | Geometric Coefficient of Variation 53 |
| Cohort 3 - ZID 2 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ZID | 4.68 L/h | — |
| Cohort 4 - WCK 6777 4 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ERT | 0.84 L/h | Geometric Coefficient of Variation 48 |
| Cohort 4 - WCK 6777 4 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ZID | 5.84 L/h | Geometric Coefficient of Variation 25 |
| Cohort 5 - ERT 3 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ERT | 0.92 L/h | Geometric Coefficient of Variation 37 |
| Cohort 6 - ZID 3 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ZID | 6.8 L/h | Geometric Coefficient of Variation 25 |
| Cohort 7 - WCK 6777 6 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ERT | 0.9 L/h | Geometric Coefficient of Variation 44 |
| Cohort 7 - WCK 6777 6 g | Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS) | Unchanged ZID | 6.77 L/h | Geometric Coefficient of Variation 12 |
Secondary
Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the terminal elimination half-life, t1/2 (h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.75 hours | Geometric Coefficient of Variation 18 |
| Cohort 1 - WCK 6777 2 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.35 hours | Geometric Coefficient of Variation 15 |
| Cohort 1 - WCK 6777 2 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 4.34 hours | Geometric Coefficient of Variation 12 |
| Cohort 1 - WCK 6777 2 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 4.09 hours | Geometric Coefficient of Variation 11 |
| Cohort 2 - ERT 2 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.76 hours | Geometric Coefficient of Variation 22 |
| Cohort 2 - ERT 2 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.83 hours | Geometric Coefficient of Variation 21 |
| Cohort 3 - ZID 2 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.81 hours | Geometric Coefficient of Variation 14 |
| Cohort 3 - ZID 2 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.60 hours | Geometric Coefficient of Variation 14 |
| Cohort 4 - WCK 6777 4 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.92 hours | Geometric Coefficient of Variation 14 |
| Cohort 4 - WCK 6777 4 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.86 hours | Geometric Coefficient of Variation 15 |
| Cohort 4 - WCK 6777 4 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.63 hours | Geometric Coefficient of Variation 15 |
| Cohort 4 - WCK 6777 4 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.57 hours | Geometric Coefficient of Variation 12 |
| Cohort 5 - ERT 3 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 4.20 hours | Geometric Coefficient of Variation 4 |
| Cohort 5 - ERT 3 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.96 hours | Geometric Coefficient of Variation 12 |
| Cohort 6 - ZID 3 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.61 hours | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.69 hours | Geometric Coefficient of Variation 9 |
| Cohort 7 - WCK 6777 6 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.71 hours | Geometric Coefficient of Variation 5 |
| Cohort 7 - WCK 6777 6 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 4.20 hours | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.87 hours | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.71 hours | Geometric Coefficient of Variation 6 |
Secondary
Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the terminal elimination half-life, t1/2 (h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.89 hours | Geometric Coefficient of Variation 19 |
| Cohort 1 - WCK 6777 2 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.55 hours | Geometric Coefficient of Variation 11 |
| Cohort 1 - WCK 6777 2 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.32 hours | Geometric Coefficient of Variation 15 |
| Cohort 1 - WCK 6777 2 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.91 hours | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.64 hours | Geometric Coefficient of Variation 19 |
| Cohort 2 - ERT 2 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.45 hours | Geometric Coefficient of Variation 19 |
| Cohort 3 - ZID 2 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.78 hours | Geometric Coefficient of Variation 15 |
| Cohort 3 - ZID 2 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.64 hours | Geometric Coefficient of Variation 12 |
| Cohort 4 - WCK 6777 4 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 3.13 hours | Geometric Coefficient of Variation 55 |
| Cohort 4 - WCK 6777 4 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.67 hours | Geometric Coefficient of Variation 21 |
| Cohort 4 - WCK 6777 4 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.38 hours | Geometric Coefficient of Variation 19 |
| Cohort 4 - WCK 6777 4 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.47 hours | Geometric Coefficient of Variation 24 |
| Cohort 5 - ERT 3 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 4.14 hours | Geometric Coefficient of Variation 4 |
| Cohort 5 - ERT 3 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.77 hours | Geometric Coefficient of Variation 10 |
| Cohort 6 - ZID 3 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.65 hours | Geometric Coefficient of Variation 7 |
| Cohort 6 - ZID 3 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.69 hours | Geometric Coefficient of Variation 3 |
| Cohort 7 - WCK 6777 6 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.70 hours | Geometric Coefficient of Variation 8 |
| Cohort 7 - WCK 6777 6 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 3.76 hours | Geometric Coefficient of Variation 17 |
| Cohort 7 - WCK 6777 6 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.65 hours | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 3.86 hours | Geometric Coefficient of Variation 18 |
Secondary
The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the accumulation ratio of the AUC, RAUC (ratio), parameter for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. RAUC is estimated as AUC(0-tau),ss (Dose 7)/AUC(0-24) (Dose 1), where the areas under the concentration-time curves from Dose 7 to the end of the dosing interval at steady state and from Dose 1 extrapolated to 24 h after Dose 1, AUC(0-tau),ss and AUC(0-24) respectively, are calculated using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). The AUC(0-tau),ss estimate assumes steady state was reached.
Time frame: =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusions
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.96 ratio | Geometric Coefficient of Variation 5 |
| Cohort 1 - WCK 6777 2 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.94 ratio | Geometric Coefficient of Variation 4 |
| Cohort 1 - WCK 6777 2 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.99 ratio | Geometric Coefficient of Variation 5 |
| Cohort 1 - WCK 6777 2 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.96 ratio | Geometric Coefficient of Variation 4 |
| Cohort 2 - ERT 2 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.99 ratio | Geometric Coefficient of Variation 3 |
| Cohort 2 - ERT 2 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.98 ratio | Geometric Coefficient of Variation 7 |
| Cohort 3 - ZID 2 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.97 ratio | Geometric Coefficient of Variation 13 |
| Cohort 3 - ZID 2 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.94 ratio | Geometric Coefficient of Variation 13 |
| Cohort 4 - WCK 6777 4 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.87 ratio | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.89 ratio | Geometric Coefficient of Variation 11 |
| Cohort 4 - WCK 6777 4 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.94 ratio | Geometric Coefficient of Variation 26 |
| Cohort 4 - WCK 6777 4 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.96 ratio | Geometric Coefficient of Variation 5 |
| Cohort 5 - ERT 3 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.89 ratio | Geometric Coefficient of Variation 9 |
| Cohort 5 - ERT 3 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.91 ratio | Geometric Coefficient of Variation 6 |
| Cohort 6 - ZID 3 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 1.01 ratio | Geometric Coefficient of Variation 8 |
| Cohort 6 - ZID 3 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 1.03 ratio | Geometric Coefficient of Variation 7 |
| Cohort 7 - WCK 6777 6 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.89 ratio | Geometric Coefficient of Variation 13 |
| Cohort 7 - WCK 6777 6 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.79 ratio | Geometric Coefficient of Variation 17 |
| Cohort 7 - WCK 6777 6 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.89 ratio | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.85 ratio | Geometric Coefficient of Variation 9 |
Secondary
The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the accumulation ratio of the Cmax, RCmax (ratio), parameter for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. RCmax is estimated as Cmax (Dose 7)/Cmax (Dose 1), where the Cmax parameters are estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h periods following Dose 1 and Dose 7, respectively.
Time frame: =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusions
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.93 ratio | Geometric Coefficient of Variation 11 |
| Cohort 1 - WCK 6777 2 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.90 ratio | Geometric Coefficient of Variation 15 |
| Cohort 1 - WCK 6777 2 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.92 ratio | Geometric Coefficient of Variation 15 |
| Cohort 1 - WCK 6777 2 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.92 ratio | Geometric Coefficient of Variation 17 |
| Cohort 2 - ERT 2 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.13 ratio | Geometric Coefficient of Variation 14 |
| Cohort 2 - ERT 2 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 1.12 ratio | Geometric Coefficient of Variation 7 |
| Cohort 3 - ZID 2 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.96 ratio | Geometric Coefficient of Variation 11 |
| Cohort 3 - ZID 2 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.98 ratio | Geometric Coefficient of Variation 11 |
| Cohort 4 - WCK 6777 4 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.98 ratio | Geometric Coefficient of Variation 12 |
| Cohort 4 - WCK 6777 4 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.85 ratio | Geometric Coefficient of Variation 40 |
| Cohort 4 - WCK 6777 4 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.97 ratio | Geometric Coefficient of Variation 7 |
| Cohort 4 - WCK 6777 4 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.86 ratio | Geometric Coefficient of Variation 37 |
| Cohort 5 - ERT 3 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.01 ratio | Geometric Coefficient of Variation 8 |
| Cohort 5 - ERT 3 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.99 ratio | Geometric Coefficient of Variation 12 |
| Cohort 6 - ZID 3 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.98 ratio | Geometric Coefficient of Variation 13 |
| Cohort 6 - ZID 3 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 1.03 ratio | Geometric Coefficient of Variation 10 |
| Cohort 7 - WCK 6777 6 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.89 ratio | Geometric Coefficient of Variation 13 |
| Cohort 7 - WCK 6777 6 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.88 ratio | Geometric Coefficient of Variation 8 |
| Cohort 7 - WCK 6777 6 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.85 ratio | Geometric Coefficient of Variation 28 |
| Cohort 7 - WCK 6777 6 g | The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.89 ratio | Geometric Coefficient of Variation 17 |
Secondary
Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Median and minimum/maximum of the Tmax,ss (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. The estimate for Tmax,ss assumes steady state has been achieved.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.52 hours |
| Cohort 1 - WCK 6777 2 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.52 hours |
| Cohort 1 - WCK 6777 2 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.52 hours |
| Cohort 1 - WCK 6777 2 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.52 hours |
| Cohort 2 - ERT 2 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.00 hours |
| Cohort 2 - ERT 2 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 1.00 hours |
| Cohort 3 - ZID 2 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 1.00 hours |
| Cohort 3 - ZID 2 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 1.00 hours |
| Cohort 4 - WCK 6777 4 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 1.02 hours |
| Cohort 4 - WCK 6777 4 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.02 hours |
| Cohort 4 - WCK 6777 4 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 1.02 hours |
| Cohort 4 - WCK 6777 4 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 1.02 hours |
| Cohort 5 - ERT 3 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.02 hours |
| Cohort 5 - ERT 3 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 2.02 hours |
| Cohort 6 - ZID 3 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.02 hours |
| Cohort 6 - ZID 3 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.02 hours |
| Cohort 7 - WCK 6777 6 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 2.07 hours |
| Cohort 7 - WCK 6777 6 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.07 hours |
| Cohort 7 - WCK 6777 6 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.07 hours |
| Cohort 7 - WCK 6777 6 g | Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.07 hours |
Secondary
Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Median and minimum/maximum of the Tmax (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 0.50 hours |
| Cohort 1 - WCK 6777 2 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 0.50 hours |
| Cohort 1 - WCK 6777 2 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 0.50 hours |
| Cohort 1 - WCK 6777 2 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 0.50 hours |
| Cohort 2 - ERT 2 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.00 hours |
| Cohort 2 - ERT 2 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 1.00 hours |
| Cohort 3 - ZID 2 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 1.03 hours |
| Cohort 3 - ZID 2 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 1.03 hours |
| Cohort 4 - WCK 6777 4 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 1.00 hours |
| Cohort 4 - WCK 6777 4 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 1.00 hours |
| Cohort 4 - WCK 6777 4 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 1.00 hours |
| Cohort 4 - WCK 6777 4 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.00 hours |
| Cohort 5 - ERT 3 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.02 hours |
| Cohort 5 - ERT 3 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 2.02 hours |
| Cohort 6 - ZID 3 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.02 hours |
| Cohort 6 - ZID 3 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.02 hours |
| Cohort 7 - WCK 6777 6 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 2.03 hours |
| Cohort 7 - WCK 6777 6 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 2.03 hours |
| Cohort 7 - WCK 6777 6 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 2.03 hours |
| Cohort 7 - WCK 6777 6 g | Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 2.03 hours |
Secondary
Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Median and minimum/maximum of the Tmin (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 23.60 hours |
| Cohort 1 - WCK 6777 2 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 23.60 hours |
| Cohort 1 - WCK 6777 2 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 23.60 hours |
| Cohort 1 - WCK 6777 2 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 18.00 hours |
| Cohort 2 - ERT 2 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 23.60 hours |
| Cohort 2 - ERT 2 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 23.65 hours |
| Cohort 3 - ZID 2 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 23.60 hours |
| Cohort 3 - ZID 2 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 23.60 hours |
| Cohort 4 - WCK 6777 4 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 23.60 hours |
| Cohort 4 - WCK 6777 4 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 23.60 hours |
| Cohort 4 - WCK 6777 4 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 23.60 hours |
| Cohort 4 - WCK 6777 4 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 23.60 hours |
| Cohort 5 - ERT 3 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 23.60 hours |
| Cohort 5 - ERT 3 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 23.60 hours |
| Cohort 6 - ZID 3 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 23.60 hours |
| Cohort 6 - ZID 3 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 23.60 hours |
| Cohort 7 - WCK 6777 6 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 23.60 hours |
| Cohort 7 - WCK 6777 6 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 23.60 hours |
| Cohort 7 - WCK 6777 6 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 23.60 hours |
| Cohort 7 - WCK 6777 6 g | Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 23.60 hours |
Secondary
Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Median and minimum/maximum of the Tmin (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group.
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 24.00 hours |
| Cohort 1 - WCK 6777 2 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 24.00 hours |
| Cohort 1 - WCK 6777 2 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 18.00 hours |
| Cohort 1 - WCK 6777 2 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 24.00 hours |
| Cohort 2 - ERT 2 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 24.00 hours |
| Cohort 2 - ERT 2 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 24.05 hours |
| Cohort 3 - ZID 2 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 24.00 hours |
| Cohort 3 - ZID 2 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 24.00 hours |
| Cohort 4 - WCK 6777 4 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 24.00 hours |
| Cohort 4 - WCK 6777 4 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 24.00 hours |
| Cohort 4 - WCK 6777 4 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 24.00 hours |
| Cohort 4 - WCK 6777 4 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 24.00 hours |
| Cohort 5 - ERT 3 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 24.00 hours |
| Cohort 5 - ERT 3 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 24.00 hours |
| Cohort 6 - ZID 3 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 24.00 hours |
| Cohort 6 - ZID 3 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 24.00 hours |
| Cohort 7 - WCK 6777 6 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 24.00 hours |
| Cohort 7 - WCK 6777 6 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 24.00 hours |
| Cohort 7 - WCK 6777 6 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 24.00 hours |
| Cohort 7 - WCK 6777 6 g | Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 24.00 hours |
Secondary
Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total clearance, CLT (L/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.34 L/h | Geometric Coefficient of Variation 10 |
| Cohort 1 - WCK 6777 2 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 23.99 L/h | Geometric Coefficient of Variation 7 |
| Cohort 1 - WCK 6777 2 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 7.07 L/h | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 7.91 L/h | Geometric Coefficient of Variation 8 |
| Cohort 2 - ERT 2 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 23.28 L/h | Geometric Coefficient of Variation 19 |
| Cohort 2 - ERT 2 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.58 L/h | Geometric Coefficient of Variation 19 |
| Cohort 3 - ZID 2 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 7.71 L/h | Geometric Coefficient of Variation 15 |
| Cohort 3 - ZID 2 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 6.58 L/h | Geometric Coefficient of Variation 18 |
| Cohort 4 - WCK 6777 4 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 8.03 L/h | Geometric Coefficient of Variation 41 |
| Cohort 4 - WCK 6777 4 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 19.06 L/h | Geometric Coefficient of Variation 24 |
| Cohort 4 - WCK 6777 4 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 6.21 L/h | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.42 L/h | Geometric Coefficient of Variation 15 |
| Cohort 5 - ERT 3 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.37 L/h | Geometric Coefficient of Variation 11 |
| Cohort 5 - ERT 3 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 15.70 L/h | Geometric Coefficient of Variation 15 |
| Cohort 6 - ZID 3 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 7.86 L/h | Geometric Coefficient of Variation 9 |
| Cohort 6 - ZID 3 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 7.86 L/h | Geometric Coefficient of Variation 11 |
| Cohort 7 - WCK 6777 6 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 6.75 L/h | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 6.99 L/h | Geometric Coefficient of Variation 16 |
| Cohort 7 - WCK 6777 6 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 15.50 L/h | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.45 L/h | Geometric Coefficient of Variation 11 |
Secondary
Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total clearance, CLT (L/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Time frame: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusion
Population: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - WCK 6777 2 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 8.28 L/h | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 25.35 L/h | Geometric Coefficient of Variation 6 |
| Cohort 1 - WCK 6777 2 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 7.50 L/h | Geometric Coefficient of Variation 8 |
| Cohort 1 - WCK 6777 2 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.39 L/h | Geometric Coefficient of Variation 9 |
| Cohort 2 - ERT 2 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 23.75 L/h | Geometric Coefficient of Variation 18 |
| Cohort 2 - ERT 2 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.63 L/h | Geometric Coefficient of Variation 13 |
| Cohort 3 - ZID 2 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 7.96 L/h | Geometric Coefficient of Variation 20 |
| Cohort 3 - ZID 2 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 6.98 L/h | Geometric Coefficient of Variation 20 |
| Cohort 4 - WCK 6777 4 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 8.54 L/h | Geometric Coefficient of Variation 30 |
| Cohort 4 - WCK 6777 4 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 6.49 L/h | Geometric Coefficient of Variation 19 |
| Cohort 4 - WCK 6777 4 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 22.09 L/h | Geometric Coefficient of Variation 16 |
| Cohort 4 - WCK 6777 4 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.62 L/h | Geometric Coefficient of Variation 16 |
| Cohort 5 - ERT 3 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.55 L/h | Geometric Coefficient of Variation 7 |
| Cohort 5 - ERT 3 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 17.83 L/h | Geometric Coefficient of Variation 23 |
| Cohort 6 - ZID 3 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 7.80 L/h | Geometric Coefficient of Variation 7 |
| Cohort 6 - ZID 3 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 7.65 L/h | Geometric Coefficient of Variation 8 |
| Cohort 7 - WCK 6777 6 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ZID | 7.89 L/h | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ERT | 1.74 L/h | Geometric Coefficient of Variation 14 |
| Cohort 7 - WCK 6777 6 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Free ERT | 19.86 L/h | Geometric Coefficient of Variation 19 |
| Cohort 7 - WCK 6777 6 g | Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma | Total ZID | 7.56 L/h | Geometric Coefficient of Variation 14 |