Infections, Bacterial
Conditions
Keywords
Normal Renal Function, end stage renal disease (ESRD), Pharmacokinetics, Gepotidacin, Renal Impairment
Brief summary
This study will be conducted to determine if altered renal function affects the plasma pharmacokinetics of gepotidacin, which will inform if dosing recommendations based upon renal impairment are required. The objective of this study is to compare the pharmacokinetics of gepotidacin administered as a 750 milligram (mg) intravenous (IV) dose in normal healthy subjects compared with subjects with mild, moderate, and severe renal impairment, and with subjects with end stage renal disease (ESRD). This is a Phase I, nonrandomized, open-label, parallel-group, multi-center, multi-part study. In Part 1, up to 16 subjects with normal renal function will be matched to approximately 8 subjects with moderate renal impairment, and approximately 8 subjects with severe renal impairment and/or subjects with ESRD not on hemodialysis for a total of approximately 32 subjects. In Part 2 (optional), approximately 4 to 8 subjects with normal renal function (if enrolled), approximately 4 to 8 subjects with mild renal impairment, and approximately 4 to 8 subjects with ESRD on hemodialysis will be enrolled for a total of approximately 12 to 24 subjects. The duration from Screening to the Follow-up Visit will be approximately 44 days for Part 1 and approximately 50 days for Part 2.
Interventions
DRUGGepotidacin
Gepotidacin after reconstitution is a clear, dark brown to dark brownish-yellow solution, free from visible particulate matter. Subjects will receive gepotidacin 750 mg single IV dose over 2 hours.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Age: Male or female subject between 18 and 80 years of age, inclusive. * Healthy subject must be in clinically stable health as determined by the investigator based on medical history, clinical laboratory results (serum chemistry, hematology, urinalysis, and serology), vital sign measurements, 12 lead ECG results, and physical examination findings. Subject with renal impairment must have clinical laboratory values consistent with their disease and are approved by the investigator. * Subject with renal impairment (mild, moderate, severe, or subjects with ESRD) may be taking medications, which in the opinion of the investigator, are believed to be therapeutic but do not affect study drug absorption, distribution, metabolism, or excretion. These medications must be stable doses taken for at least 7 days before the first dose of study drug. * Subject with normal renal function or renal impairment (estimated Glomerular Filtration Rate \[eGFR\] corresponding to the calculated eGFR \[the estimated eGFR may be rounded to the nearest integer\]) at Screening. * Subjects with ESRD on hemodialysis should be on hemodialysis for at least 3 months before Screening and is able to tolerate a hemodialysis treatment lasting 3 to 4 hours with blood flow rates of \>200 milliliter (mL)/minute (min). * Alanine aminotransferase (ALT) and bilirubin \<1.5 × upper limit of normal (ULN; isolated bilirubin \>1.5 × ULN is acceptable, if bilirubin is fractionated and direct bilirubin \<35%). * Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 18.5 and 40 kg/square meter (m\^2), inclusive. * Male or Female. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies: Nonreproductive potential defined as: * Premenopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, or Documented bilateral oophorectomy * Postmenopausal defined as 12 months of continuous spontaneous amenorrhea (in questionable cases a blood sample will be obtained to test for simultaneous follicle-stimulating hormone) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. Reproductive potential and agrees to follow 1 of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential requirements from 30 days prior to the first dose until completion of the Follow-up Visit. For subjects with indeterminate pregnancy test results or a persistently low human chorionic gonadotropin results, nonpregnancy status must be documented by other means (subjects with ESRD only). * Capable of giving signed informed consent as described in protocol, which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
Exclusion criteria
* Subject has a clinically significant abnormality in past medical history or at the Screening physical examination (excluding renal insufficiency and other related stable medical conditions within the renally impaired population of subjects \[e.g., hypertension, diabetes, or anemia, which should be stable for at least 3 months before the first dose of study drug\]) that in the investigator's opinion may place the subject at risk or interfere with outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, neurologic, gastrointestinal (GI), respiratory, hematologic, or immunologic disease. Subject has any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study drug, or any other condition that may place the subject at risk, in the opinion of the investigator. * Subject has a functioning renal transplant. * Subject with renal impairment has a systolic blood pressure outside the range of 90 to 200 millimeter of mercury (mm Hg), a diastolic blood pressure outside the range of 45 to 110 mm Hg, or a heart rate outside the range of 40 to 120 beats per minute (bpm). * Subject with renal impairment has a hemoglobin value \<9 grams (g)/decilitre (dL). * Female subject has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic. * Use of a systemic antibiotic within 30 days of Screening * Within 2 months before Screening, either a confirmed history of Clostridium difficile diarrhoea infection or a past positive Clostridium difficile toxin test. * Subject has a history of drug and/or alcohol abuse within 6 months before Screening, as determined by the investigator, or subject has a positive drug screen at Screening or upon admission to the clinic. For subjects with renal impairment, a positive drug screen result related to the use of prescription medications is allowed per investigator review and approval, and tetrahydrocannabinol use is allowed per investigator review and approval. * History of sensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) medical monitor, contraindicates their participation. * History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic uses heparin to maintain IV cannula patency). * Subject has used medications known to affect the elimination of serum creatinine (e.g., trimethoprim or cimetidine) or competitors of renal tubular secretion (e.g., probenecid) within 30 days before dosing. * Subjects cannot use any over-the-counter, or prescription medication (except for hormonal contraceptives and/or acetaminophen), vitamin supplement, or herbal medication within 7 days (or 5 half-lives, whichever is longer) before dosing and during the study within 7 days before dosing and during the study. * Subjects with normal renal function have a presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study treatment. A subject with renal impairment with stable hepatitis C who has normal liver function test results is allowed with investigator approval. * A positive test for human immunodeficiency virus antibody. * Subject has clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at Screening or Day -1 (and Day 7 for Group F only), other than those associated with underlying renal conditions or other stable medical conditions consistent with the disease process. * Subject with normal renal function has a baseline corrected QT interval using the Fridericia formula (QTcF) of \>450 milliseconds (msec) and subject with renal impairment has a baseline QTcF of \>480 msec. * Donation of blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. * Previous exposure to gepotidacin within 12 months prior to the first dosing day. * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer). * Subject is unable to comply with all study procedures, in the opinion of the investigator. * The subject should not participate in the study, in the opinion of the investigator or Sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity . Blood samples were collected at the indicated time-points, during the study. The Pharmacokinetic (PK) Parameter Population consisted of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. The PK Population consisted of all participant's, who received at least 1 dose of gepotidacin and had evaluable PK data. |
| AUC (0-inf) of Gepotidacin for Part 2 | Pre-dose, 0.25 hours, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both. | AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for gepotidacin. Blood samples were collected at the indicated time-points, during the study. |
| Maximum Observed Plasma Concentration (Cmax) of Gepotidacin for Part 1 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | Cmax, is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected, at the indicated time points for analysis of gepotidacin. |
| Cmax of Gepotidacin for Part 2 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on during treatment period 1 and 2 both. | Cmax, is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected, at the indicated time points for analysis of gepotidacin. |
| Total Amount Excreted in Urine (Ae Total), Part 1 | Pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period | Urine samples from the participants were collected during the study. Ae total assessed the, total unchanged drug (total amount of drug excreted in urine), which was calculated, by adding all the fractions of drug gepotidacin collected, at the indicated time points. No formal statistical analysis of group comparison was planned for urine PK parameters. |
| Ae Total of Gepotidacin for Part 2 | Pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during both treatment period 1 and 2 | Urine samples, from the participants were collected during the study. Ae total assessed the, total unchanged drug (total amount of drug excreted in urine), which was calculated, by adding all the fractions of drug gepotidacin collected, at the indicated time points. Urine samples were collected at pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period. Only those participant's available at the specified time points were analyzed. No formal statistical analysis of group comparison was planned for urine PK parameters. |
| Percentage of the Given Dose Excreted in Urine (fe%) of Gepotidacin for Part 1 | At pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period | The fe% measured the percentage of the given dose of drug gepotidacin, excreted in urine. It was calculated as: Ae total divided by the dose administered multiplied by 100. |
| fe% of Gepotidacin for Part 2 | At pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose in each of the two treatment periods | The fe% measured the percentage of the given dose of drug gepotidacin, excreted in urine. It was calculated as: Ae total divided by the dose administered multiplied by 100. No formal statistical analysis of group comparison was planned for urine PK parameters. Only those participants available at the specified time points were analyzed. |
| Renal Clearance (CLr) of Gepotidacin for Part 1 | At pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period | Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time via renal clearance pathways, expressed as volume (Liter) per unit of time (hour). The renal clearance was calculated by Ae total divided by AUC from hour 0 to the last measurable plasma concentration AUC (0-t). Urine samples were collected at pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period. No formal statistical analysis of group comparison was planned for urine PK parameters. |
| CLr of Gepotidacin for Part 2 | At pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose in each of the two treatment periods | Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time via renal clearance pathways, expressed as volume (Liter) per unit of time (hour). Urine samples were collected at pre-dose (0.0), 0 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose in each of the two treatment periods. Only those participant's available at the specified time points were analyzed. No formal statistical analysis of group comparison was planned for urine PK parameters. |
| AUC (t0-t1) of Gepotidacin for Part 2 | Dialysate fluid were to be collected on Day 1 after dosing (Period 1 only) at pre-dose from 0 to 4 hours | Partial area under the curve estimated from predialyzer samples collected from start of dialysis (t0) to end of dialysis (t1). Only applicable to Part 2 ESRD on hemodialysis (before hemodialysis) arm.. |
| Dialysis Clearance (CLD) of Gepotidacin for Part 2 | Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1 | CLD measured the dialysis clearance of gepotidacin over the specified duration in the study and indicates how quickly gepotidacin is cleared out from blood or plasma. Only applicable to Part 2 ESRD on hemodialysis (before hemodialysis) arm. |
| Fraction (%) of the Dose Removed by Hemodialysis From 0 to 4 Hours After the Start of Hemodialysis (Frem%[0-4]) of Gepotidacin for Part 2 | Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1 | Dialysate samples were collected at specified time points in the study. Frem is defined as the fraction (dose in percentage) removed by the process of hemodialysis from 0 to 4 hours after the start of hemodialysis (or to the end of dialysis if less than 4 hours) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC (0-t) of Gepotidacin for Part 2 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both. | Serial blood samples were collected at specified time-points for PK analysis. The data for Area under the concentration-time curve from time 0 (predose) to time of last quantifiable concentration for gepotidacin were reported. |
| Systemic Clearance (CL) of Gepotidacin for Part 1 | At pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose during the single treatment period. | Serial blood samples were collected at specified time-points for PK analysis. Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-inf). |
| CL of Gepotidacin for Part 2 | At pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose in each of the two treatment periods | Serial blood samples were collected at specified time-points for PK analysis. Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-inf). |
| Terminal Elimination Rate Constant (lambda_z) of Gepotidacin for Part 1 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | Serial blood samples were collected at specified time-points for PK analysis. It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour. |
| Lambda_z of Gepotidacin for Part 2 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on during treatment period 1 and 2 both | Serial blood samples were collected at specified time-points for PK analysis. It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour. |
| Terminal Phase Half-life (t1/2) of Gepotidacin for Part 1 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | Serial blood samples were collected at specified time-points for PK analysis. t1/2 is defined as the time required by the concentration of the drug to reach half of its original value. |
| t1/2 of Gepotidacin for Part 2 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both. | Serial blood samples were collected at specified time-points for PK analysis. t1/2 is defined as the time required by the concentration of the drug to reach half of its original value. |
| Time to Maximum Plasma Concentration (Tmax) of Gepotidacin for Part1 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | Serial blood samples were collected at specified time-points for PK analysis. Tmax was defined as the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. |
| Tmax of Gepotidacin for Part 2 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both. | Serial blood samples were collected at specified time-points for PK analysis. Tmax was defined as the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. |
| Volume of Distribution at Steady State of Parent Drug (Vss) of Gepotidacin for Part 1 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. |
| Vss of Gepotidacin for Part 2 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both. | Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. |
| Volume of Distribution of the Terminal Phase (Vz) of Gepotidacin for Part 1 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz is the apparent volume of distribution at terminal phase. Volume of distribution of the terminal phase was calculated as total administered dose of gepotidacin divided by AUC (0-inf) multiplied by the rate constant. |
| Vz of Gepotidacin for Part 2 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both. | Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz is the apparent volume of distribution at terminal phase. Volume of distribution of the terminal phase was calculated as total administered dose of gepotidacin divided by AUC (0-inf) multiplied by the rate constant. |
| Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Up to 16 Days | Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and corrected Q to T interval (QTc). The data for abnormal ECG recordings not clinically significant (NCS) and clinically significant (CS), have been reported at specific timepoints during the study. No formal analysis of group comparison was planned for dialysate PK parameters |
| Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | at pre-dose (0.0), 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 36, and 36 to 48 hours post-dose during the single treatment period | Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Ae(t1-t2) of Gepotidacin for Part 2 | Pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during both treatment period 1 and 2 | Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment; and predose, 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours for participant's with normal renal function. NA indicates data is not available due to insufficient participants.Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Total Amount of Unchanged Amount of Drug Removed by Hemodialysis (Arem) From Time 0 to 1 Hour After the Start of Hemodialysis (Arem[0-1]), Arem (1-2), Arem (2-3), Arem (3-4) for Part 2 | Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1Dialysate fluid were collected at 1, 2, 3, and 4 hours post-dose in Period 1 only | Arem is defined as the total amount of drug removed using the hemodialysis method at different timepoints namely Arem (0-1), measured the amount of drug removed by hemodialysis from time 0 to 1 hour after the start of hemodialysis; Arem (1-2), measured the amount of drug removed by hemodialysis from time 1 to 2 hours after the start of hemodialysis; Arem(2-3) ), measured the amount of drug removed by hemodialysis from time 2 to 3 hour, Arem (3-4), measured the amount of drug removed by hemodialysis from hemodialysis from time 3 to 4 hours after the start of hemodialysis (or to the end of dialysis if \<4 hours). Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | At Pre-dose, 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours | Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment; and predose, 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours for participant's with normal renal function. |
| Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Up to 23 Days | Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and corrected Q to T interval (QTc). The data for abnormal ECG recordings not clinically significant (NCS) and clinically significant (CS), have been reported at specific time points during the study. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). NA indicates data was not available |
| Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | Baseline and up to 16 Days | Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was reported. Baseline was defined as the latest pre-dose assessment. Change from Baseline, was defined as post Baseline values minus the values at Baseline. |
| Change From Baseline in Vitals- SBP and DBP, Part 2 | Baseline and up to 23 Days | Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Change From Baseline in Vitals- Pulse Rate, Part 1 | Baseline and up to 16 Days | Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for pulse rate was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment |
| Change From Baseline in Vitals- Pulse Rate, Part 2 | Baseline and Up to 23 Days | Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for pulse rate was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1 | Up to 16 Days | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. |
| Number of Participants With Any AEs and Any SAEs for Part 2 | Up to 23 Days | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. |
| Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1 | Up to 17 Days | The adverse events reported by the participants were classified as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 as life-threatening. The data for clinical laboratory findings with values of Grade 3 or higher, have been reported. |
| Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 2 | Up to 24 Days | The adverse events reported by the participants were classified as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 as life-threatening. The data for clinical laboratory findings with values of Grade 3 or higher, have been reported. |
| Number of Participants With Abnormal Physical Examination Results for Part 1 | Up to 16 Days | Physical exam were to be performed by a qualified individual. A complete physical examination included, at a minimum, an assessment of the cardiovascular, respiratory, GI, and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This data was not collected. |
| Number of Participants With Abnormal Physical Examination Results for Part 2 | Up to 23 Days | Physical exam were to be performed by a qualified individual. A complete physical examination included, at a minimum, an assessment of the cardiovascular, respiratory, GI, and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This data was not collected. |
| AUC (0-t) of Gepotidacin for Part 1 | Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | Blood samples were collected at specified time-points for PK analysis. The data for Area under the concentration-time curve from time 0 (predose) to time of last quantifiable concentration for gepotidacin were reported. |
Countries
United States
Participant flow
Recruitment details
A 2-part study, conducted in participant's with varying degree of renal impairment (RI) which enrolled 32 participants, wherein, 24 participants were enrolled in Part 1 and 8 participants in Part 2. The study was conducted, at 3 centers in United States of America from 29 June 2016 to 20 June 2017.
Pre-assignment details
A total of 43 participants were screened of which 8 were screen-failures and 32 were enrolled in the study and 3 participants were reserve participants and were no longer required in the study .
Participants by arm
| Arm | Count |
|---|---|
| Normal, Part 1 The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) \>= 90 milliliter per minute per 1.73 meter\^2 or estimated Clcr \>= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1. | 8 |
| Moderate, Part 1 The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter\^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1. | 8 |
| Severe/ESRD Not on Hemodialysis, Part 1 The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR \< 30 milliliter per minute per 1.73 meter\^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1. | 8 |
| ESRD on Hemodialysis, Part 2 The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in this period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (Period 1) and gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2). | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Normal, Part 1 | Moderate, Part 1 | Severe/ESRD Not on Hemodialysis, Part 1 | ESRD on Hemodialysis, Part 2 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.5 Years STANDARD_DEVIATION 10.78 | 72.0 Years STANDARD_DEVIATION 7.05 | 61.4 Years STANDARD_DEVIATION 12.49 | 51.8 Years STANDARD_DEVIATION 7.09 | 61.6 Years STANDARD_DEVIATION 2.72 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized Multiple: African American/African/White | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White: White/Caucasian/European | 7 Participants | 6 Participants | 5 Participants | 0 Participants | 18 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 4 Participants | 7 Participants | 23 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 4 / 8 | 4 / 8 | 4 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Ae Total of Gepotidacin for Part 2
Urine samples, from the participants were collected during the study. Ae total assessed the, total unchanged drug (total amount of drug excreted in urine), which was calculated, by adding all the fractions of drug gepotidacin collected, at the indicated time points. Urine samples were collected at pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period. Only those participant's available at the specified time points were analyzed. No formal statistical analysis of group comparison was planned for urine PK parameters.
Time frame: Pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during both treatment period 1 and 2
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Ae Total of Gepotidacin for Part 2 | 280.49 milligram | Geometric Coefficient of Variation 15.2 |
| Moderate, Part 1 | Ae Total of Gepotidacin for Part 2 | 7.87 milligram | Geometric Coefficient of Variation 96.4 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Ae Total of Gepotidacin for Part 2 | 10.87 milligram | Geometric Coefficient of Variation 64.7 |
Primary
Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1
AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity . Blood samples were collected at the indicated time-points, during the study. The Pharmacokinetic (PK) Parameter Population consisted of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. The PK Population consisted of all participant's, who received at least 1 dose of gepotidacin and had evaluable PK data.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Population: PK Parameter Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1 | 14838 Nanogram*hour per milliliter | Geometric Coefficient of Variation 20.7 |
| Moderate, Part 1 | Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1 | 22367 Nanogram*hour per milliliter | Geometric Coefficient of Variation 17 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1 | 28545 Nanogram*hour per milliliter | Geometric Coefficient of Variation 21.4 |
90% CI: [0.902, 2.519]
90% CI: [1.151, 3.215]
Primary
AUC (0-inf) of Gepotidacin for Part 2
AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for gepotidacin. Blood samples were collected at the indicated time-points, during the study.
Time frame: Pre-dose, 0.25 hours, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.
Population: PK Parameter Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | AUC (0-inf) of Gepotidacin for Part 2 | 14838 Nanogram*hour per milliliter | Geometric Coefficient of Variation 20.7 |
| Moderate, Part 1 | AUC (0-inf) of Gepotidacin for Part 2 | 35239 Nanogram*hour per milliliter | Geometric Coefficient of Variation 95 |
| Severe/ESRD Not on Hemodialysis, Part 1 | AUC (0-inf) of Gepotidacin for Part 2 | 60461 Nanogram*hour per milliliter | Geometric Coefficient of Variation 140.5 |
90% CI: [1.421, 3.969]
90% CI: [2.438, 6.81]
Primary
AUC (t0-t1) of Gepotidacin for Part 2
Partial area under the curve estimated from predialyzer samples collected from start of dialysis (t0) to end of dialysis (t1). Only applicable to Part 2 ESRD on hemodialysis (before hemodialysis) arm..
Time frame: Dialysate fluid were to be collected on Day 1 after dosing (Period 1 only) at pre-dose from 0 to 4 hours
Population: PK parameter Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate, Part 1 | AUC (t0-t1) of Gepotidacin for Part 2 | 1062 Nanogram*hour per milliliter | Geometric Coefficient of Variation 36.3 |
Primary
CLr of Gepotidacin for Part 2
Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time via renal clearance pathways, expressed as volume (Liter) per unit of time (hour). Urine samples were collected at pre-dose (0.0), 0 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose in each of the two treatment periods. Only those participant's available at the specified time points were analyzed. No formal statistical analysis of group comparison was planned for urine PK parameters.
Time frame: At pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose in each of the two treatment periods
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | CLr of Gepotidacin for Part 2 | 19.24 Liter per hour | Geometric Coefficient of Variation 18.8 |
| Moderate, Part 1 | CLr of Gepotidacin for Part 2 | 0.29 Liter per hour | Geometric Coefficient of Variation 101.7 |
| Severe/ESRD Not on Hemodialysis, Part 1 | CLr of Gepotidacin for Part 2 | 0.10 Liter per hour | Geometric Coefficient of Variation 277.5 |
Primary
Cmax of Gepotidacin for Part 2
Cmax, is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected, at the indicated time points for analysis of gepotidacin.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on during treatment period 1 and 2 both.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Cmax of Gepotidacin for Part 2 | 4498 nanogram per milliliter | Geometric Coefficient of Variation 16.3 |
| Moderate, Part 1 | Cmax of Gepotidacin for Part 2 | 10123 nanogram per milliliter | Geometric Coefficient of Variation 216.3 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Cmax of Gepotidacin for Part 2 | 26839 nanogram per milliliter | Geometric Coefficient of Variation 797.1 |
90% CI: [0.891, 5.681]
90% CI: [2.363, 15.062]
Primary
Dialysis Clearance (CLD) of Gepotidacin for Part 2
CLD measured the dialysis clearance of gepotidacin over the specified duration in the study and indicates how quickly gepotidacin is cleared out from blood or plasma. Only applicable to Part 2 ESRD on hemodialysis (before hemodialysis) arm.
Time frame: Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Dialysis Clearance (CLD) of Gepotidacin for Part 2 | 6.63 Liter per hour | Geometric Coefficient of Variation 15.8 |
Primary
fe% of Gepotidacin for Part 2
The fe% measured the percentage of the given dose of drug gepotidacin, excreted in urine. It was calculated as: Ae total divided by the dose administered multiplied by 100. No formal statistical analysis of group comparison was planned for urine PK parameters. Only those participants available at the specified time points were analyzed.
Time frame: At pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose in each of the two treatment periods
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | fe% of Gepotidacin for Part 2 | 37.40 Percentage of gepotidacin | Geometric Coefficient of Variation 15.2 |
| Moderate, Part 1 | fe% of Gepotidacin for Part 2 | 1.05 Percentage of gepotidacin | Geometric Coefficient of Variation 96.4 |
| Severe/ESRD Not on Hemodialysis, Part 1 | fe% of Gepotidacin for Part 2 | 1.45 Percentage of gepotidacin | Geometric Coefficient of Variation 64.7 |
Primary
Fraction (%) of the Dose Removed by Hemodialysis From 0 to 4 Hours After the Start of Hemodialysis (Frem%[0-4]) of Gepotidacin for Part 2
Dialysate samples were collected at specified time points in the study. Frem is defined as the fraction (dose in percentage) removed by the process of hemodialysis from 0 to 4 hours after the start of hemodialysis (or to the end of dialysis if less than 4 hours)
Time frame: Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Fraction (%) of the Dose Removed by Hemodialysis From 0 to 4 Hours After the Start of Hemodialysis (Frem%[0-4]) of Gepotidacin for Part 2 | 5.89 Percentage of gepotidacin removed | Geometric Coefficient of Variation 26.2 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Gepotidacin for Part 1
Cmax, is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected, at the indicated time points for analysis of gepotidacin.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Population: PK Parameter Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Maximum Observed Plasma Concentration (Cmax) of Gepotidacin for Part 1 | 4498 nanogram per milliliter | Geometric Coefficient of Variation 16.3 |
| Moderate, Part 1 | Maximum Observed Plasma Concentration (Cmax) of Gepotidacin for Part 1 | 5306 nanogram per milliliter | Geometric Coefficient of Variation 16 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Maximum Observed Plasma Concentration (Cmax) of Gepotidacin for Part 1 | 7084 nanogram per milliliter | Geometric Coefficient of Variation 23.3 |
90% CI: [0.467, 2.977]
90% CI: [0.624, 3.975]
Primary
Percentage of the Given Dose Excreted in Urine (fe%) of Gepotidacin for Part 1
The fe% measured the percentage of the given dose of drug gepotidacin, excreted in urine. It was calculated as: Ae total divided by the dose administered multiplied by 100.
Time frame: At pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Percentage of the Given Dose Excreted in Urine (fe%) of Gepotidacin for Part 1 | 37.40 Percentage of gepotidacin | Geometric Coefficient of Variation 15.2 |
| Moderate, Part 1 | Percentage of the Given Dose Excreted in Urine (fe%) of Gepotidacin for Part 1 | 22.11 Percentage of gepotidacin | Geometric Coefficient of Variation 39.4 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Percentage of the Given Dose Excreted in Urine (fe%) of Gepotidacin for Part 1 | 7.92 Percentage of gepotidacin | Geometric Coefficient of Variation 68.3 |
Primary
Renal Clearance (CLr) of Gepotidacin for Part 1
Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time via renal clearance pathways, expressed as volume (Liter) per unit of time (hour). The renal clearance was calculated by Ae total divided by AUC from hour 0 to the last measurable plasma concentration AUC (0-t). Urine samples were collected at pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period. No formal statistical analysis of group comparison was planned for urine PK parameters.
Time frame: At pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Renal Clearance (CLr) of Gepotidacin for Part 1 | 19.24 Liter per hour | Geometric Coefficient of Variation 18.8 |
| Moderate, Part 1 | Renal Clearance (CLr) of Gepotidacin for Part 1 | 7.58 Liter per hour | Geometric Coefficient of Variation 44.3 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Renal Clearance (CLr) of Gepotidacin for Part 1 | 2.13 Liter per hour | Geometric Coefficient of Variation 84.3 |
Primary
Total Amount Excreted in Urine (Ae Total), Part 1
Urine samples from the participants were collected during the study. Ae total assessed the, total unchanged drug (total amount of drug excreted in urine), which was calculated, by adding all the fractions of drug gepotidacin collected, at the indicated time points. No formal statistical analysis of group comparison was planned for urine PK parameters.
Time frame: Pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period
Population: PK Parameter Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Total Amount Excreted in Urine (Ae Total), Part 1 | 280.49 milligram. | Geometric Coefficient of Variation 15.2 |
| Moderate, Part 1 | Total Amount Excreted in Urine (Ae Total), Part 1 | 165.86 milligram. | Geometric Coefficient of Variation 39.4 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Total Amount Excreted in Urine (Ae Total), Part 1 | 59.40 milligram. | Geometric Coefficient of Variation 68.3 |
Secondary
Ae(t1-t2) of Gepotidacin for Part 2
Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment; and predose, 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours for participant's with normal renal function. NA indicates data is not available due to insufficient participants.Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time frame: Pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during both treatment period 1 and 2
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (24-36) (n=8,2,1) | 5.38 milligram | Geometric Coefficient of Variation 52.1 |
| Normal, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (12-24) (n=8,3, 3) | 12.30 milligram | Geometric Coefficient of Variation 55.3 |
| Normal, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (8-12) (n=8,3,3) | 9.11 milligram | Geometric Coefficient of Variation 86.9 |
| Normal, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (36-48) (n=8,2,0) | 3.00 milligram | Geometric Coefficient of Variation 42.8 |
| Moderate, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (24-36) (n=8,2,1) | 0.45 milligram | Geometric Coefficient of Variation 154.4 |
| Moderate, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (8-12) (n=8,3,3) | 0.72 milligram | Geometric Coefficient of Variation 32.1 |
| Moderate, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (12-24) (n=8,3, 3) | 0.81 milligram | Geometric Coefficient of Variation 147.5 |
| Moderate, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (36-48) (n=8,2,0) | 0.14 milligram | Geometric Coefficient of Variation 133.2 |
| Moderate, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (0-8)(n=0,3,3) | 5.56 milligram | Geometric Coefficient of Variation 123.4 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (12-24) (n=8,3, 3) | 1.31 milligram | Geometric Coefficient of Variation 52.5 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (24-36) (n=8,2,1) | 0.75 milligram | — |
| Severe/ESRD Not on Hemodialysis, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (0-8)(n=0,3,3) | 8.12 milligram | Geometric Coefficient of Variation 73.8 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Ae(t1-t2) of Gepotidacin for Part 2 | Ae (8-12) (n=8,3,3) | 1.16 milligram | Geometric Coefficient of Variation 31.5 |
Secondary
AUC (0-t) of Gepotidacin for Part 1
Blood samples were collected at specified time-points for PK analysis. The data for Area under the concentration-time curve from time 0 (predose) to time of last quantifiable concentration for gepotidacin were reported.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | AUC (0-t) of Gepotidacin for Part 1 | 14582 Nanogram*hour per milliliter | Geometric Coefficient of Variation 20.8 |
| Moderate, Part 1 | AUC (0-t) of Gepotidacin for Part 1 | 21883 Nanogram*hour per milliliter | Geometric Coefficient of Variation 17.1 |
| Severe/ESRD Not on Hemodialysis, Part 1 | AUC (0-t) of Gepotidacin for Part 1 | 27886 Nanogram*hour per milliliter | Geometric Coefficient of Variation 21.4 |
90% CI: [0.894, 2.52]
90% CI: [1.139, 3.212]
Secondary
AUC (0-t) of Gepotidacin for Part 2
Serial blood samples were collected at specified time-points for PK analysis. The data for Area under the concentration-time curve from time 0 (predose) to time of last quantifiable concentration for gepotidacin were reported.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | AUC (0-t) of Gepotidacin for Part 2 | 14582 Nanogram*hour per milliliter | Geometric Coefficient of Variation 20.8 |
| Moderate, Part 1 | AUC (0-t) of Gepotidacin for Part 2 | 34633 Nanogram*hour per milliliter | Geometric Coefficient of Variation 95.8 |
| Severe/ESRD Not on Hemodialysis, Part 1 | AUC (0-t) of Gepotidacin for Part 2 | 59311 Nanogram*hour per milliliter | Geometric Coefficient of Variation 143.3 |
90% CI: [1.414, 3.989]
90% CI: [2.422, 6.831]
Secondary
Change From Baseline in Vitals- Pulse Rate, Part 1
Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for pulse rate was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment
Time frame: Baseline and up to 16 Days
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 8 hour | -1.0 Beats per minute | Standard Deviation 13.4 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Follow-up | -0.6 Beats per minute | Standard Deviation 10.34 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 2 - 24 hour | 1.0 Beats per minute | Standard Deviation 13.06 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 12 hour | -0.1 Beats per minute | Standard Deviation 12.31 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1- 1.5 hour | 0.1 Beats per minute | Standard Deviation 9.28 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 3 - 48 hour | -1.4 Beats per minute | Standard Deviation 10.76 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 4 hour | 0.1 Beats per minute | Standard Deviation 6.49 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1- 2 hour | 1.8 Beats per minute | Standard Deviation 7.13 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 2 - 36 hour | 1.6 Beats per minute | Standard Deviation 9.56 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 12 hour | 3.4 Beats per minute | Standard Deviation 4.78 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1- 1.5 hour | 1.6 Beats per minute | Standard Deviation 4.21 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1- 2 hour | 4.1 Beats per minute | Standard Deviation 3.23 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 4 hour | 0.4 Beats per minute | Standard Deviation 8.14 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 8 hour | 1.8 Beats per minute | Standard Deviation 7.5 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 2 - 24 hour | -0.8 Beats per minute | Standard Deviation 7.85 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 2 - 36 hour | -0.5 Beats per minute | Standard Deviation 5.37 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 3 - 48 hour | -0.1 Beats per minute | Standard Deviation 7.88 |
| Moderate, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Follow-up | 0.6 Beats per minute | Standard Deviation 8.45 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 4 hour | 2.0 Beats per minute | Standard Deviation 5.63 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1- 1.5 hour | 3.5 Beats per minute | Standard Deviation 4.41 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 2 - 36 hour | 0.6 Beats per minute | Standard Deviation 5.24 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1- 2 hour | 4.1 Beats per minute | Standard Deviation 5.03 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Follow-up | 0.0 Beats per minute | Standard Deviation 7.43 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 12 hour | 3.4 Beats per minute | Standard Deviation 1.92 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 1 - 8 hour | 0.8 Beats per minute | Standard Deviation 4.46 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 3 - 48 hour | -1.8 Beats per minute | Standard Deviation 7.34 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 1 | Pulse rate, Day 2 - 24 hour | -2.3 Beats per minute | Standard Deviation 5.55 |
Secondary
Change From Baseline in Vitals- Pulse Rate, Part 2
Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for pulse rate was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time frame: Baseline and Up to 23 Days
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 1- 2 hour, (n=8) | 0.4 beats per minute | Standard Deviation 8.78 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 1 - 4 hour, (n=8) | 3.4 beats per minute | Standard Deviation 9.09 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 1 - 8 hour, (n=8) | 4.4 beats per minute | Standard Deviation 9.46 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 1 - 12 hour, (n=7) | 4.4 beats per minute | Standard Deviation 10.21 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 2 - 24 hour, (n=8) | 2.5 beats per minute | Standard Deviation 7.11 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 2 - 36 hour, (n=8) | 6.1 beats per minute | Standard Deviation 9.96 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 3 - 48 hour, (n=7) | 3.6 beats per minute | Standard Deviation 5.88 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day, 8-2 hour (n=8) | 4.8 beats per minute | Standard Deviation 10.38 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 8-4 hour (n=7) | 2.1 beats per minute | Standard Deviation 5.08 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 8-8 hour ,(n=8) | 3.4 beats per minute | Standard Deviation 7.69 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 8-12 hour (n=8) | 4.7 beats per minute | Standard Deviation 10.05 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 9-24 hour (n=8) | 4.0 beats per minute | Standard Deviation 11.51 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day9-36 hour (n=8) | 8.9 beats per minute | Standard Deviation 16.19 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Day 10-48 hour (n=8) | 3.6 beats per minute | Standard Deviation 11.04 |
| Normal, Part 1 | Change From Baseline in Vitals- Pulse Rate, Part 2 | Pulse rate, Follow-up (n=8) | 3.8 beats per minute | Standard Deviation 10.22 |
Secondary
Change From Baseline in Vitals- SBP and DBP, Part 2
Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time frame: Baseline and up to 23 Days
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 1- 2 hour, (n=8) | -0.5 Milliliter of mercury | Standard Deviation 14.91 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 1 - 4 hour (n=8) | 8.6 Milliliter of mercury | Standard Deviation 16.66 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 1 - 8 hour, (n=8) | -0.6 Milliliter of mercury | Standard Deviation 23.93 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 1 - 12 hour, (n=8) | -4.8 Milliliter of mercury | Standard Deviation 17.68 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 2 - 24 hour, (n=8) | 1.4 Milliliter of mercury | Standard Deviation 9.69 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 2 - 36 hour (n=8) | 3.9 Milliliter of mercury | Standard Deviation 10.33 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 3 - 48 hour, (n=8) | 6.5 Milliliter of mercury | Standard Deviation 5.53 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 8-2 hour (n=8) | -2.0 Milliliter of mercury | Standard Deviation 8.16 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 8-4 hour (n=8) | -4.4 Milliliter of mercury | Standard Deviation 7.46 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 8-8 hour (n=8) | -14.8 Milliliter of mercury | Standard Deviation 14.5 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 8-12 hour (n=6) | -8.3 Milliliter of mercury | Standard Deviation 7.92 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 9-24 hour (n=8) | 5.9 Milliliter of mercury | Standard Deviation 23.94 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 9-36 hour (n=8) | 2.3 Milliliter of mercury | Standard Deviation 20.11 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Day 10-48 hour (n=8) | 12.6 Milliliter of mercury | Standard Deviation 19.72 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | SBP, Follow-up, (n=8) | 0.5 Milliliter of mercury | Standard Deviation 11.86 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 1- 2 hour, (n=8) | 4.3 Milliliter of mercury | Standard Deviation 11.31 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 1 - 4 hour, (n=8) | 3.6 Milliliter of mercury | Standard Deviation 9.83 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 1 - 8 hour, (n=8) | -1.5 Milliliter of mercury | Standard Deviation 11.7 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 1 - 12 hour (n=8) | -2.3 Milliliter of mercury | Standard Deviation 9.54 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 2 - 24 hour (n=8) | 4.6 Milliliter of mercury | Standard Deviation 9.68 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 2 - 36 hour,(n=8) | 3.3 Milliliter of mercury | Standard Deviation 6.11 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 3 - 48 hour (n=7) | 3.0 Milliliter of mercury | Standard Deviation 10.1 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 8-2 hour, (n=8) | -2.1 Milliliter of mercury | Standard Deviation 10.49 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 8-4 hour , (n=8) | -2.5 Milliliter of mercury | Standard Deviation 9.41 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 8- 8 hour,(n=8) | -6.9 Milliliter of mercury | Standard Deviation 8.48 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 8-12 hour, (n=8) | -9.5 Milliliter of mercury | Standard Deviation 10.03 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 9-24 hour, (n=8) | 6.4 Milliliter of mercury | Standard Deviation 9.41 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 9-36 hour (n=8) | 2.6 Milliliter of mercury | Standard Deviation 13.41 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Day 10-48 hour (n=8) | 5.9 Milliliter of mercury | Standard Deviation 11.74 |
| Normal, Part 1 | Change From Baseline in Vitals- SBP and DBP, Part 2 | DBP, Follow-up (n=8) | 2.3 Milliliter of mercury | Standard Deviation 6.34 |
Secondary
Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1
Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was reported. Baseline was defined as the latest pre-dose assessment. Change from Baseline, was defined as post Baseline values minus the values at Baseline.
Time frame: Baseline and up to 16 Days
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 12 hour, | -3.4 Milliliter of mercury | Standard Deviation 12.29 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1- 2 hour, | 6.9 Milliliter of mercury | Standard Deviation 12.54 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 4 hour | -0.9 Milliliter of mercury | Standard Deviation 12.15 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 8 hour, | 1.3 Milliliter of mercury | Standard Deviation 12.69 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1- 1.5 hour, | 3.1 Milliliter of mercury | Standard Deviation 2.36 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 2 - 24 hour, | -1.1 Milliliter of mercury | Standard Deviation 13.28 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 2 - 36 hour | 0.5 Milliliter of mercury | Standard Deviation 3.74 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 3 - 48 hour | -1.0 Milliliter of mercury | Standard Deviation 10.72 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Follow-up | 0.8 Milliliter of mercury | Standard Deviation 3.28 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1- 1.5 hour | 0.1 Milliliter of mercury | Standard Deviation 3.91 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1- 2 hour, | 5.8 Milliliter of mercury | Standard Deviation 7.15 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 4 hour | 3.0 Milliliter of mercury | Standard Deviation 5.5 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 8 hour | 4.9 Milliliter of mercury | Standard Deviation 6.06 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 12 hour | 2.9 Milliliter of mercury | Standard Deviation 6.36 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 2 - 24 hour | 2.3 Milliliter of mercury | Standard Deviation 5.5 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 2 - 36 hour | 3.1 Milliliter of mercury | Standard Deviation 8.22 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 3 - 48 hour | 5.0 Milliliter of mercury | Standard Deviation 7.69 |
| Normal, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Follow-up | 2.6 Milliliter of mercury | Standard Deviation 5.48 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Follow-up | 0.5 Milliliter of mercury | Standard Deviation 11.6 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1- 1.5 hour, | 6.8 Milliliter of mercury | Standard Deviation 11.94 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1- 1.5 hour | -1.3 Milliliter of mercury | Standard Deviation 3.92 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 8 hour | -4.3 Milliliter of mercury | Standard Deviation 10.55 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1- 2 hour, | 8.3 Milliliter of mercury | Standard Deviation 13.39 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 2 - 24 hour | 1.0 Milliliter of mercury | Standard Deviation 5.55 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 2 - 36 hour | -0.8 Milliliter of mercury | Standard Deviation 13.07 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 4 hour | 3.4 Milliliter of mercury | Standard Deviation 5.42 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1- 2 hour, | 1.3 Milliliter of mercury | Standard Deviation 3.99 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 3 - 48 hour | 0.6 Milliliter of mercury | Standard Deviation 6.48 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 8 hour, | 5.9 Milliliter of mercury | Standard Deviation 7.3 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Follow-up | 8.3 Milliliter of mercury | Standard Deviation 13.06 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 12 hour | -0.5 Milliliter of mercury | Standard Deviation 9.61 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 12 hour, | 14.1 Milliliter of mercury | Standard Deviation 12.89 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 3 - 48 hour | 7.8 Milliliter of mercury | Standard Deviation 9.1 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 4 hour | -2.4 Milliliter of mercury | Standard Deviation 8.14 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 2 - 24 hour, | 5.3 Milliliter of mercury | Standard Deviation 6.65 |
| Moderate, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 2 - 36 hour | 14.4 Milliliter of mercury | Standard Deviation 13.02 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 2 - 24 hour, | -4.1 Milliliter of mercury | Standard Deviation 11.46 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 2 - 36 hour | -0.4 Milliliter of mercury | Standard Deviation 9.12 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 3 - 48 hour | -6.0 Milliliter of mercury | Standard Deviation 18.18 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 2 - 24 hour | -2.3 Milliliter of mercury | Standard Deviation 4.17 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Follow-up | -4.8 Milliliter of mercury | Standard Deviation 18.16 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Follow-up | -1.8 Milliliter of mercury | Standard Deviation 6.58 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1- 1.5 hour | -3.5 Milliliter of mercury | Standard Deviation 7.19 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1- 2 hour, | 0.4 Milliliter of mercury | Standard Deviation 4.07 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 2 - 36 hour | -3.5 Milliliter of mercury | Standard Deviation 3.96 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 4 hour | 1.5 Milliliter of mercury | Standard Deviation 4.99 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1- 1.5 hour, | -3.3 Milliliter of mercury | Standard Deviation 13.77 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1- 2 hour, | -4.4 Milliliter of mercury | Standard Deviation 12.73 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 8 hour | -2.4 Milliliter of mercury | Standard Deviation 6.95 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 4 hour | 1.0 Milliliter of mercury | Standard Deviation 13.03 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 8 hour, | 6.0 Milliliter of mercury | Standard Deviation 12.75 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | SBP, Day 1 - 12 hour, | 4.6 Milliliter of mercury | Standard Deviation 6.3 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 1 - 12 hour | -3.6 Milliliter of mercury | Standard Deviation 4.66 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 | DBP, Day 3 - 48 hour | -5.3 Milliliter of mercury | Standard Deviation 5.87 |
Secondary
CL of Gepotidacin for Part 2
Serial blood samples were collected at specified time-points for PK analysis. Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-inf).
Time frame: At pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose in each of the two treatment periods
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | CL of Gepotidacin for Part 2 | 50.55 Liter per hour | Geometric Coefficient of Variation 20.7 |
| Moderate, Part 1 | CL of Gepotidacin for Part 2 | 21.28 Liter per hour | Geometric Coefficient of Variation 95 |
| Severe/ESRD Not on Hemodialysis, Part 1 | CL of Gepotidacin for Part 2 | 12.40 Liter per hour | Geometric Coefficient of Variation 140.5 |
Secondary
Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe
Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time frame: at pre-dose (0.0), 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 36, and 36 to 48 hours post-dose during the single treatment period
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae(36-48) (n=8,7) | 2.66 milligram | Geometric Coefficient of Variation 50.3 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae (0-6) (n=8, 8) | 119.79 milligram | Geometric Coefficient of Variation 50 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae(24-36 (n=8, 8) | 5.25 milligram | Geometric Coefficient of Variation 25.4 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae (6-12) (n=8, 8) | 21.67 milligram | Geometric Coefficient of Variation 30.7 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae (12-24) (n=8, 8) | 12.81 milligram | Geometric Coefficient of Variation 40.8 |
| Moderate, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae (6-12) (n=8, 8) | 8.26 milligram | Geometric Coefficient of Variation 44.8 |
| Moderate, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae (12-24) (n=8, 8) | 4.42 milligram | Geometric Coefficient of Variation 160 |
| Moderate, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae(24-36 (n=8, 8) | 2.89 milligram | Geometric Coefficient of Variation 29.8 |
| Moderate, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae (0-6) (n=8, 8) | 39.54 milligram | Geometric Coefficient of Variation 94.9 |
| Moderate, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe | Ae(36-48) (n=8,7) | 1.17 milligram | Geometric Coefficient of Variation 71 |
Secondary
Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal
Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment; and predose, 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours for participant's with normal renal function.
Time frame: At Pre-dose, 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | Ae(0-2) | 135.53 milligram | Geometric Coefficient of Variation 21 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | Ae (2-4) | 59.95 milligram | Geometric Coefficient of Variation 56.7 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | Ae (4-6) | 19.90 milligram | Geometric Coefficient of Variation 18.4 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | Ae (6-8) | 19.47 milligram | Geometric Coefficient of Variation 70.5 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | Ae (8-12) | 9.11 milligram | Geometric Coefficient of Variation 86.9 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | Ae(12-24) | 12.30 milligram | Geometric Coefficient of Variation 55.3 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | Ae(24-36) | 5.38 milligram | Geometric Coefficient of Variation 52.1 |
| Normal, Part 1 | Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal | Ae(36-48) | 3.00 milligram | Geometric Coefficient of Variation 42.8 |
Secondary
Lambda_z of Gepotidacin for Part 2
Serial blood samples were collected at specified time-points for PK analysis. It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on during treatment period 1 and 2 both
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Lambda_z of Gepotidacin for Part 2 | 0.06027 Per hour | Geometric Coefficient of Variation 11.9 |
| Moderate, Part 1 | Lambda_z of Gepotidacin for Part 2 | 0.07338 Per hour | Geometric Coefficient of Variation 8.4 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Lambda_z of Gepotidacin for Part 2 | 0.06428 Per hour | Geometric Coefficient of Variation 16.4 |
Secondary
Number of Participants With Abnormal 12-lead ECG Readings for Part 2
Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and corrected Q to T interval (QTc). The data for abnormal ECG recordings not clinically significant (NCS) and clinically significant (CS), have been reported at specific time points during the study. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). NA indicates data was not available
Time frame: Up to 23 Days
Population: Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1- Baseline, Abnormal CS (n=8,8) | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1 - Baseline, Abnormal NCS (n=8,8) | 6 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1- 2 hour, Abnormal, NCS (n=8,0) | 6 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1- 2 hour, Abnormal, CS (n=8,0) | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1 - 4 hour, Abnormal, NCS (n=8,0) | 7 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1- 4 hour, Abnormal CS (n=8,0) | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1 - 8 hour, Abnormal NCS (n=8,0) | 7 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1 - 8 hour, Abnormal, CS (n=8,0) | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1 - 12 hour, Abnormal NCS (n=8,0) | 6 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1 - 12 hour, Abnormal, CS (n=8,0) | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 2 - 24 hour, Abnormal NCS (n=8,0) | 7 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 2 - 24 hour, Abnormal, CS (n=8,0) | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 2 - 36 hour, Abnormal NCS (n=8,0) | 8 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 2 - 36 hour, Abnormal, CS (n=8,0) | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 3 - 48 hour, Abnormal NCS (n=8,0) | 7 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day3 - 48 hour, Abnormal, CS (n=8,0) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Follow-up, Abnormal NCS (n=0,8) | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Follow-up, Abnormal CS (n=0,8) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 8- 2 hour, Abnormal, NCS (n=0,8) | 8 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1- Baseline, Abnormal CS (n=8,8) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 8- 2 hour, Abnormal, CS (n=0,8) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 1 - Baseline, Abnormal NCS (n=8,8) | 7 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 8 - 4 hour, Abnormal, NCS (n=0,8) | 8 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 8- 4 hour, Abnormal CS (n=0,8) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 8 - 8 hour, Abnormal NCS (n=0,8) | 7 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 8 - 8 hour, Abnormal, CS (n=0,8) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 8 - 12 hour, Abnormal NCS (n=0,8) | 8 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 8 - 12 hour, Abnormal, CS (n=0,8) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 9- 24 hour, Abnormal, NCS (n=0,8) | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 9- 24 hour, Abnormal, CS (n=0,8) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 9 - 36 hour, Abnormal, NCS (n=0,8) | 8 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 9- 36 hour, Abnormal CS (n=0,8) | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 10 - 48 hour, Abnormal NCS (n=0,8) | 7 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead ECG Readings for Part 2 | Day 10 - 48 hour, Abnormal, CS (n=0,8) | 0 Participants |
Secondary
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1
Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and corrected Q to T interval (QTc). The data for abnormal ECG recordings not clinically significant (NCS) and clinically significant (CS), have been reported at specific timepoints during the study. No formal analysis of group comparison was planned for dialysate PK parameters
Time frame: Up to 16 Days
Population: The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 1.5 hour, Abnormal, NCS | 5 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 4 hour, Abnormal CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Follow-up, Abnormal CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 24 hour, Abnormal, CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 8 hour, Abnormal NCS | 2 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day3 - 48 hour, Abnormal, CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 24 hour, Abnormal NCS | 3 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 8 hour, Abnormal, CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 1.5 hour, Abnormal, CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 12 hour, Abnormal, CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 12 hour, Abnormal NCS | 2 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Baseline, Abnormal, CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 3 - 48 hour, Abnormal NCS | 2 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 2 hour, Abnormal, NCS | 3 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Baseline, Abnormal, NCS | 3 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 36 hour, Abnormal, CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 2 hour, Abnormal, CS | 0 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Follow-up, Abnormal NCS | 3 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 36 hour, Abnormal NCS | 2 Participants |
| Normal, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 4 hour, Abnormal, NCS | 2 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day3 - 48 hour, Abnormal, CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Baseline, Abnormal, NCS | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Baseline, Abnormal, CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 1.5 hour, Abnormal, NCS | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 1.5 hour, Abnormal, CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 2 hour, Abnormal, NCS | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 2 hour, Abnormal, CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 4 hour, Abnormal, NCS | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 4 hour, Abnormal CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 8 hour, Abnormal NCS | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 8 hour, Abnormal, CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 12 hour, Abnormal NCS | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 12 hour, Abnormal, CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 24 hour, Abnormal NCS | 7 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 24 hour, Abnormal, CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 36 hour, Abnormal NCS | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 36 hour, Abnormal, CS | 0 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 3 - 48 hour, Abnormal NCS | 6 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Follow-up, Abnormal NCS | 5 Participants |
| Moderate, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Follow-up, Abnormal CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Baseline, Abnormal, CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 24 hour, Abnormal, CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 2 hour, Abnormal, CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Follow-up, Abnormal CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 36 hour, Abnormal NCS | 6 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 2 hour, Abnormal, NCS | 6 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Follow-up, Abnormal NCS | 5 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 36 hour, Abnormal, CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 1.5 hour, Abnormal, CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Baseline, Abnormal, NCS | 7 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 3 - 48 hour, Abnormal NCS | 5 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 1.5 hour, Abnormal, NCS | 6 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 12 hour, Abnormal NCS | 7 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 8 hour, Abnormal, CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 4 hour, Abnormal, NCS | 7 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 12 hour, Abnormal, CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1 - 8 hour, Abnormal NCS | 6 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day3 - 48 hour, Abnormal, CS | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 2 - 24 hour, Abnormal NCS | 5 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 | Day 1- 4 hour, Abnormal CS | 0 Participants |
Secondary
Number of Participants With Abnormal Physical Examination Results for Part 1
Physical exam were to be performed by a qualified individual. A complete physical examination included, at a minimum, an assessment of the cardiovascular, respiratory, GI, and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This data was not collected.
Time frame: Up to 16 Days
Population: Safety Population. This data was not collected.
Secondary
Number of Participants With Abnormal Physical Examination Results for Part 2
Physical exam were to be performed by a qualified individual. A complete physical examination included, at a minimum, an assessment of the cardiovascular, respiratory, GI, and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This data was not collected.
Time frame: Up to 23 Days
Population: Safety Population: This data was not collected.
Secondary
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.
Time frame: Up to 16 Days
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal, Part 1 | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1 | Any SAE | 0 Participants |
| Normal, Part 1 | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1 | Any AE | 0 Participants |
| Moderate, Part 1 | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1 | Any SAE | 0 Participants |
| Moderate, Part 1 | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1 | Any AE | 3 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1 | Any SAE | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1 | Any AE | 4 Participants |
Secondary
Number of Participants With Any AEs and Any SAEs for Part 2
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.
Time frame: Up to 23 Days
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal, Part 1 | Number of Participants With Any AEs and Any SAEs for Part 2 | Any SAE | 0 Participants |
| Normal, Part 1 | Number of Participants With Any AEs and Any SAEs for Part 2 | Any AE | 4 Participants |
| Moderate, Part 1 | Number of Participants With Any AEs and Any SAEs for Part 2 | Any SAE | 0 Participants |
| Moderate, Part 1 | Number of Participants With Any AEs and Any SAEs for Part 2 | Any AE | 3 Participants |
Secondary
Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1
The adverse events reported by the participants were classified as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 as life-threatening. The data for clinical laboratory findings with values of Grade 3 or higher, have been reported.
Time frame: Up to 17 Days
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1 | Serum or plasma creatinine, Grade 3 or higher | 0 Participants |
| Normal, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1 | Serum glucose, Grade 3 or higher | 0 Participants |
| Moderate, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1 | Serum or plasma creatinine, Grade 3 or higher | 0 Participants |
| Moderate, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1 | Serum glucose, Grade 3 or higher | 0 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1 | Serum or plasma creatinine, Grade 3 or higher | 5 Participants |
| Severe/ESRD Not on Hemodialysis, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1 | Serum glucose, Grade 3 or higher | 1 Participants |
Secondary
Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 2
The adverse events reported by the participants were classified as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 as life-threatening. The data for clinical laboratory findings with values of Grade 3 or higher, have been reported.
Time frame: Up to 24 Days
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 2 | Serum or plasma creatinine, Grade 3 or higher | 8 Participants |
| Normal, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 2 | Serum glucose, Grade 3 or higher | 2 Participants |
| Moderate, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 2 | Serum or plasma creatinine, Grade 3 or higher | 0 Participants |
| Moderate, Part 1 | Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 2 | Serum glucose, Grade 3 or higher | 0 Participants |
Secondary
Systemic Clearance (CL) of Gepotidacin for Part 1
Serial blood samples were collected at specified time-points for PK analysis. Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-inf).
Time frame: At pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose during the single treatment period.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Systemic Clearance (CL) of Gepotidacin for Part 1 | 50.55 Liter per hour | Geometric Coefficient of Variation 20.7 |
| Moderate, Part 1 | Systemic Clearance (CL) of Gepotidacin for Part 1 | 33.53 Liter per hour | Geometric Coefficient of Variation 17 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Systemic Clearance (CL) of Gepotidacin for Part 1 | 26.27 Liter per hour | Geometric Coefficient of Variation 21.4 |
Secondary
t1/2 of Gepotidacin for Part 2
Serial blood samples were collected at specified time-points for PK analysis. t1/2 is defined as the time required by the concentration of the drug to reach half of its original value.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.
Population: Pharmacokinetic Parameter Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal, Part 1 | t1/2 of Gepotidacin for Part 2 | 11.663 hours |
| Moderate, Part 1 | t1/2 of Gepotidacin for Part 2 | 9.455 hours |
| Severe/ESRD Not on Hemodialysis, Part 1 | t1/2 of Gepotidacin for Part 2 | 11.121 hours |
Secondary
Terminal Elimination Rate Constant (lambda_z) of Gepotidacin for Part 1
Serial blood samples were collected at specified time-points for PK analysis. It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Terminal Elimination Rate Constant (lambda_z) of Gepotidacin for Part 1 | 0.06027 Per hour | Geometric Coefficient of Variation 11.9 |
| Moderate, Part 1 | Terminal Elimination Rate Constant (lambda_z) of Gepotidacin for Part 1 | 0.06369 Per hour | Geometric Coefficient of Variation 16.1 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Terminal Elimination Rate Constant (lambda_z) of Gepotidacin for Part 1 | 0.06266 Per hour | Geometric Coefficient of Variation 13.4 |
Secondary
Terminal Phase Half-life (t1/2) of Gepotidacin for Part 1
Serial blood samples were collected at specified time-points for PK analysis. t1/2 is defined as the time required by the concentration of the drug to reach half of its original value.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Population: PK Parameter Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal, Part 1 | Terminal Phase Half-life (t1/2) of Gepotidacin for Part 1 | 11.663 hours |
| Moderate, Part 1 | Terminal Phase Half-life (t1/2) of Gepotidacin for Part 1 | 11.421 hours |
| Severe/ESRD Not on Hemodialysis, Part 1 | Terminal Phase Half-life (t1/2) of Gepotidacin for Part 1 | 11.246 hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Gepotidacin for Part1
Serial blood samples were collected at specified time-points for PK analysis. Tmax was defined as the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Population: Pharmacokinetic Parameter Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal, Part 1 | Time to Maximum Plasma Concentration (Tmax) of Gepotidacin for Part1 | 2.000 hours |
| Moderate, Part 1 | Time to Maximum Plasma Concentration (Tmax) of Gepotidacin for Part1 | 2.000 hours |
| Severe/ESRD Not on Hemodialysis, Part 1 | Time to Maximum Plasma Concentration (Tmax) of Gepotidacin for Part1 | 2.000 hours |
Secondary
Tmax of Gepotidacin for Part 2
Serial blood samples were collected at specified time-points for PK analysis. Tmax was defined as the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.
Population: PK Parameter Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal, Part 1 | Tmax of Gepotidacin for Part 2 | 2.000 hours |
| Moderate, Part 1 | Tmax of Gepotidacin for Part 2 | 2.000 hours |
| Severe/ESRD Not on Hemodialysis, Part 1 | Tmax of Gepotidacin for Part 2 | 1.575 hours |
Secondary
Total Amount of Unchanged Amount of Drug Removed by Hemodialysis (Arem) From Time 0 to 1 Hour After the Start of Hemodialysis (Arem[0-1]), Arem (1-2), Arem (2-3), Arem (3-4) for Part 2
Arem is defined as the total amount of drug removed using the hemodialysis method at different timepoints namely Arem (0-1), measured the amount of drug removed by hemodialysis from time 0 to 1 hour after the start of hemodialysis; Arem (1-2), measured the amount of drug removed by hemodialysis from time 1 to 2 hours after the start of hemodialysis; Arem(2-3) ), measured the amount of drug removed by hemodialysis from time 2 to 3 hour, Arem (3-4), measured the amount of drug removed by hemodialysis from hemodialysis from time 3 to 4 hours after the start of hemodialysis (or to the end of dialysis if \<4 hours). Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time frame: Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1Dialysate fluid were collected at 1, 2, 3, and 4 hours post-dose in Period 1 only
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal, Part 1 | Total Amount of Unchanged Amount of Drug Removed by Hemodialysis (Arem) From Time 0 to 1 Hour After the Start of Hemodialysis (Arem[0-1]), Arem (1-2), Arem (2-3), Arem (3-4) for Part 2 | Arem (0-1), (n=8) | 18.22 milligram | Geometric Coefficient of Variation 27.7 |
| Normal, Part 1 | Total Amount of Unchanged Amount of Drug Removed by Hemodialysis (Arem) From Time 0 to 1 Hour After the Start of Hemodialysis (Arem[0-1]), Arem (1-2), Arem (2-3), Arem (3-4) for Part 2 | Arem (1-2), (n=8) | 12.42 milligram | Geometric Coefficient of Variation 34.8 |
| Normal, Part 1 | Total Amount of Unchanged Amount of Drug Removed by Hemodialysis (Arem) From Time 0 to 1 Hour After the Start of Hemodialysis (Arem[0-1]), Arem (1-2), Arem (2-3), Arem (3-4) for Part 2 | Arem (2-3), (n=8) | 8.93 milligram | Geometric Coefficient of Variation 32.5 |
| Normal, Part 1 | Total Amount of Unchanged Amount of Drug Removed by Hemodialysis (Arem) From Time 0 to 1 Hour After the Start of Hemodialysis (Arem[0-1]), Arem (1-2), Arem (2-3), Arem (3-4) for Part 2 | Arem (3-4), (n=6) | 5.35 milligram | Geometric Coefficient of Variation 36.6 |
Secondary
Volume of Distribution at Steady State of Parent Drug (Vss) of Gepotidacin for Part 1
Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Volume of Distribution at Steady State of Parent Drug (Vss) of Gepotidacin for Part 1 | 255 Liter | Geometric Coefficient of Variation 21.7 |
| Moderate, Part 1 | Volume of Distribution at Steady State of Parent Drug (Vss) of Gepotidacin for Part 1 | 223 Liter | Geometric Coefficient of Variation 14.8 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Volume of Distribution at Steady State of Parent Drug (Vss) of Gepotidacin for Part 1 | 181 Liter | Geometric Coefficient of Variation 23.5 |
Secondary
Volume of Distribution of the Terminal Phase (Vz) of Gepotidacin for Part 1
Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz is the apparent volume of distribution at terminal phase. Volume of distribution of the terminal phase was calculated as total administered dose of gepotidacin divided by AUC (0-inf) multiplied by the rate constant.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Volume of Distribution of the Terminal Phase (Vz) of Gepotidacin for Part 1 | 839 Liter | Geometric Coefficient of Variation 25.3 |
| Moderate, Part 1 | Volume of Distribution of the Terminal Phase (Vz) of Gepotidacin for Part 1 | 527 Liter | Geometric Coefficient of Variation 29.1 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Volume of Distribution of the Terminal Phase (Vz) of Gepotidacin for Part 1 | 419 Liter | Geometric Coefficient of Variation 27 |
Secondary
Vss of Gepotidacin for Part 2
Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Vss of Gepotidacin for Part 2 | 255 Liter | Geometric Coefficient of Variation 21.7 |
| Moderate, Part 1 | Vss of Gepotidacin for Part 2 | 114 Liter | Geometric Coefficient of Variation 335.6 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Vss of Gepotidacin for Part 2 | 49 Liter | Geometric Coefficient of Variation 938.8 |
Secondary
Vz of Gepotidacin for Part 2
Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz is the apparent volume of distribution at terminal phase. Volume of distribution of the terminal phase was calculated as total administered dose of gepotidacin divided by AUC (0-inf) multiplied by the rate constant.
Time frame: Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal, Part 1 | Vz of Gepotidacin for Part 2 | 839 Liter | Geometric Coefficient of Variation 25.3 |
| Moderate, Part 1 | Vz of Gepotidacin for Part 2 | 290 Liter | Geometric Coefficient of Variation 90.8 |
| Severe/ESRD Not on Hemodialysis, Part 1 | Vz of Gepotidacin for Part 2 | 193 Liter | Geometric Coefficient of Variation 161.3 |