Bacterial Infection
Conditions
Keywords
Aztreonam, Ceftazidime-Avibactam, Efficacy, Healthy, Pharmacokinetics, Population, Safety
Brief summary
This is a Phase I, open-label, non-randomized, single center study in 48 healthy adult male and female subjects, aged 18 to 45 years. This study is aimed to investigate the safety and pharmacokinetics of ceftazidime-avibactam (AVYCAZ) combined with aztreonam (ATM), AVYCAZ alone, and ATM alone. The study will have 6 arms, arms 1-4 are the single drug administration treatment groups and will include AVYCAZ per label dosing, AVYCAZ as a continuous infusion (CI), ATM per label dosing, and ATM as a CI. Arms 5 and 6 are the two AVYCAZ and ATM combination drug administration treatment groups. The duration of subject participation will be up to 44 days, and the total length of the study will be 15 months. The primary objective of this study is to describe the safety of two dosing regimens of AVYCAZ combined with ATM relative to AVYCAZ alone, and ATM alone in healthy adult subjects.
Detailed description
This is a Phase I, open-label, non-randomized, single center study in 48 healthy adult male and female subjects, aged 18 to 45 years. This study is aimed to investigate the safety and pharmacokinetics of ceftazidime-avibactam (AVYCAZ) combined with aztreonam (ATM), AVYCAZ alone, and ATM alone. The study will have 6 arms, arms 1-4 are the single drug administration treatment groups and will include AVYCAZ per label dosing, AVYCAZ as a continuous infusion (CI), ATM per label dosing, and ATM as a continuous infusion (CI). Arms 5 and 6 are the two AVYCAZ and ATM combination drug administration treatment groups. The duration of subject participation will be up to 44 days, and the total length of the study will be 15 months. The primary objective of this study is to describe the safety of two dosing regimens of AVYCAZ combined with ATM relative to AVYCAZ alone, and ATM alone in healthy adult subjects. The secondary objectives of this study are to; 1) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone at the population level in healthy adult subjects; 2) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone following initiation of dosing on day 1 in healthy adult subjects; and 3) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone following multiple daily dosing in healthy adult subjects.
Interventions
DRUGAZACTAM
A synthetic monobactam antibiotic originally isolated from Chromobacterium violaceum
An antibacterial combination product containing ceftazidime and avibactam
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provide a signed and dated written informed consent. 2. Be able to understand and willing to comply with study procedures, restrictions, and requirements, as determined by the Principal Investigator (PI). 3. Male and female volunteers aged 18 to 45 years inclusive. 4. Suitable veins for cannulation or repeated venipuncture. 5. Subject must be in good general health as judged by the investigator as determined by medical history, vital signs\*, body mass index (BMI) and body weight\*\*, clinical laboratory values\*\*\*, and physical examination (PE). \*Oral temp \<38.0 degrees Celsius/100.4 degrees Fahrenheit; pulse 50 to 100 bpm; systolic blood pressure 90 to 140 mm Hg, and diastolic blood pressure 55 to 90 mmHg. \*\*BMI between 19-33 kg/m\^2 and body weight \> / = 50 kg \*\*\*Clinical chemistry, hematology, coagulation and urinalysis results within the clinical laboratory reference ranges; clinical laboratory values outside these ranges, if considered by the site investigator to be clinically insignificant, are also acceptable 6. Sexually active female subjects must be of non-childbearing potential\*\*\*\* or must use a highly effective method of birth control\*\*\*\*\*. \*\*\*\*Non-childbearing potential is defined as being post-menopausal for at least 18 months or surgically sterile via hysterectomy, bilateral oophorectomy, or tubal sterilization. \*\*\*\*\*Sexually active female subjects of childbearing potential must avoid becoming pregnant by using one of the following acceptable methods of birth control for 30 days prior to study product dosing and must be maintained for 30 days after last dose of study product: Intrauterine contraceptive device; OR Approved hormonal contraceptives (such as birth control pills, skin patches, Implanon(R), Nexplanon(R), DepoProvera(R) or NuvaRing(R)); OR Birth control must be captured on the appropriate data collection form. 7. Sexually active male subjects must be vasectomized or agree to use barrier contraception (condom with spermicide) from first dose of study product until 30 days following the last dose of study product. 8. Nonsmokers defined as abstinence from cigarette smoking or use of nicotine-containing products for 6 months prior to enrollment into the study.
Exclusion criteria
1. History of any clinically significant (CS) disease or disorder, medical/surgical procedure, or trauma within 4 weeks prior to the first administration of study product(s)\*. \*In the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study 2. History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. Known history of a clinically important allergy/hypersensitivity to AVI, any monobactam, any beta-lactam and/or L-arginine. 4. Receipt of probenecid or furosemide within 14 days prior to study enrollment. 5. Receipt of any antibiotics within 14 days prior to study enrollment. 6. Receipt of prescription medications (except birth control pills or hormone replacement in females) within 14 days prior to study enrollment, unless in the opinion of site investigator the medication will not interfere with the study procedures or impact subject safety. 7. Receipt of non-antibiotic medications that interacts with OAT3\*\* within 14 days prior to study enrollment. \*\*Adefovir, Anagliptin, Baricitinib, Cefaclor, Cimetidine, Ciprofloxacin (Systemic), Clofarabine, Eluxadoline, Empagliflozin, Furosemide, Ketoprofen, Methotrexate, Mycophenolate, PEMEtrexed, Penicillin G (Parenteral/Aqueous), Penicillin G Benzathine, Penicillin G Procaine, Penicillin V Benzathine, Penicillin V Potassium, Zidovudine 8. Receipt of herbal and dietary supplements (including St. John's Wort) within 14 days prior to study enrollment. 9. ALT or AST laboratory value above the ULN as defined in the toxicity table. 10. Prolonged QTcF (\> 450 msec) or shortened QTcF (\< 340 msec) or family history of long QT syndrome. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG\*\*\*. \*\*\*Abnormalities that may interfere with interpretation of QTc interval changes per the medical judgment of the PI. 11. Any positive result on screening for human immunodeficiency virus (HIV) serum hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody. 12. Creatinine clearance equal or less than 80 mL/minute (measured by Cockcroft-Gault method). 13. History of Clostridium difficile infection in past 90 days. 14. Known or suspected history of drug or alcohol abuse within the last 5 years, as judged by the PI. 15. Positive screen for drugs of abuse, cotinine (nicotine), or alcohol at screening and at admission to the study site prior to the first administration of the study products(s). 16. Received a new chemical entity (compound not approved for marketing) or participated in a study that included drug treatment within 1 month of the first dose of study product(s) for study \*\*\*\*. \*\*\*\*Period of exclusion begins at the time of the last visit of the prior study. Note: subjects consented and screened, but not dosed in this study or a previous Phase I study will not be excluded. 17. Previous participation in the present study. 18. Involvement in the planning and/or conduct of the study. 19. Any ongoing/recent (during screening) medical complaints that may interfere with analysis of study data or are considered unlikely to comply with study procedures, restrictions, and requirements \*\*\*\*\*. \*\*\*\*\*Judgment by the PI that the subject should not participate in the study. 20. Known history of past or current epilepsy or seizure disorders, excluding febrile seizures of childhood.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Day 1 through Day 11 | Adverse events include local and systemic reactions. All Grade 2 (moderate) adverse events were reported, regardless of relationship to study product. Number of participants with an AE are summarized by MedDRA system organ class (SOC). Each participant is only counted once per SOC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Day 1 and Day 7 | Mean and standard deviation (SD) of the RCmax PK parameter were estimated for ceftazidime, avibactam, and/or aztreonam by dividing the Cmax on Day 7 by the Cmax on Day 1. Cmax (ug/mL) was estimated from plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. |
| Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Day 7 | Mean and standard deviation (SD) of the AUC(0-inf) (µg\*hr/mL) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis. |
| Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Day 1 | Mean and standard deviation (SD) of the AUC(0-Tau) (µg\*hr/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis using linear trapezoidal linear interpolation method for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. AVYCAZ CI and ATM CI were not reported. |
| Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Day 1 through Day 14 | Number of participants with an AE are summarized by MedDRA system organ class (SOC) and severity. Each participant is only counted once at the highest severity recorded. For clinical laboratory tests, mild abnormal laboratory values that were not, in the investigator's opinion, medically significant were not reported as adverse events. |
| Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Day 1 | Mean and standard deviation (SD) of the Cmax (ug/mL) PK parameter after the first dose were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis. |
| Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Day 7 | Mean and standard deviation (SD) of the Cmax (ug/mL) PK parameter following multiple daily dosing were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis. |
| Minimum Plasma Concentration of Study Drug at the End of the Dosing Interval on Day 7 (Cmin) | Day 7 | Mean and standard deviation (SD) of the Cmin (ug/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. Cmin was not provided on day 7 because it was the last dosage of the study product administered; Cmin was therefore not calculated for this terminal elimination profile since the minimum concentration after a final dose would only reflect the last time point after Cmax that a blood sample is obtained, or the assay's limit of quantitation. It is therefore not comparable to Cmin calculated on prior days. |
| Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Day 1 and Day 7 | Mean and standard deviation (SD) of the RAUC PK parameter were estimated for ceftazidime, avibactam, and/or aztreonam by dividing the AUC(0-8) (avibactam and ceftazidime) or AUC(0-6) (aztreonam) on Day 7 by the AUC(0-Tau) on Day 1. AUC(0-8) and AUC(0-6) (µg\*hr/mL) on Day 7 and AUC(0-Tau) (µg\*hr/mL) on Day 1 were estimated from plasma concentration-time data using Non-compartmental analysis with the linear trapezoidal linear interpolation method for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. |
| Renal Clearance of Study Drug (CLR) | Day 1 | Mean and standard deviation (SD) of the CLR (L/h) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma and urine concentration-time data using Non-compartmental analysis. Renal clearance was calculated as Ae(0-8)/AUC(0-8) for ceftazidime and avibactam and as AE(0-4)/AUC(0-4) for aztreonam where Ae(0-8) and Ae(0-4) are the amounts of study drug excreted into the urine from time of dosing to 8 or 4 h post-dose, respectively, and AUC(0-8) and AUC(0-4) are the areas under the plasma concentration-time curve from time of dosing to 8 or 4 h post-dose, respectively. |
| Concentration of Study Drug at Steady State After Continuous Infusion (Css) | Day 1 | Mean and standard deviation (SD) of the Css (ug/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data for AVYCAZ CI and ATM CI. |
| Total Body Plasma Clearance of Study Drug (CL) | Day 7 | Mean and standard deviation (SD) of the CL (L/h) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis. |
| Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Day 1 | Mean and standard deviation (SD) of the Tmax (h) PK parameter after the first dose were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis. |
| Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Day 7 | Mean and standard deviation (SD) of the Tmax (h) PK parameter following multiple daily dosing were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis. |
| Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Day 7 | Mean and standard deviation (SD) of the Vss (L) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis. |
| Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Day 1 | Mean and standard deviation (SD) of the Cmin (ug/mL) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. |
Countries
United States
Participant flow
Recruitment details
Participants were healthy adult male and female subjects age 18-45, inclusively. Participants were enrolled between 09JUL2019 and 06NOV2020 and were recruited from the community around the clinical site.
Participants by arm
| Arm | Count |
|---|---|
| AVYCAZ IV 2.5g dose of ceftazidime-avibactam (AVYCAZ) administered intravenously as a 2-hour infusion, every 8 hours for 7 days. | 8 |
| AVYCAZ CI 2.5g dose of AVYCAZ administered intravenously as a 2-hour infusion once, then 0.32g dose per hour daily as a continuous infusion (CI) (7.5 g/day) for 7 days. | 8 |
| ATM IV 2g dose of aztreonam (ATM) administered intravenously as a 2-hour infusion, every 6 hours for 7 days. | 8 |
| ATM CI 2g of ATM administered intravenously as a 2-hour infusion once, then 0.33g dose administered intravenously per hour, daily as a continuous infusion (CI) (8 g/day) for 7 days. | 8 |
| AVYCAZ + ATM 1.5 2.5g dose of AVYCAZ administered intravenously as a 2-hour infusion, every 8 hours for 7 days, and a 1.5g dose of ATM administered intravenously as a 2-hour infusion, every 6 hours for 7 days. | 8 |
| AVYCAZ + ATM 2.0 2.5 g dose of AVYCAZ administered intravenously as a 2-hour infusion every 8 hours for 7 days, and a 2g dose of ATM as a 2-hour infusion every 6 hours for 7 days. | 8 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | AVYCAZ IV | AVYCAZ CI | ATM IV | ATM CI | AVYCAZ + ATM 1.5 | AVYCAZ + ATM 2.0 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 48 Participants |
| Age, Continuous | 37.4 years STANDARD_DEVIATION 5.5 | 36.4 years STANDARD_DEVIATION 7 | 34.5 years STANDARD_DEVIATION 5.9 | 30.8 years STANDARD_DEVIATION 6.5 | 28.5 years STANDARD_DEVIATION 3.8 | 33.8 years STANDARD_DEVIATION 4.6 | 33.5 years STANDARD_DEVIATION 6.2 |
| BMI | 25.74 kg/m^2 STANDARD_DEVIATION 2.92 | 27.65 kg/m^2 STANDARD_DEVIATION 3.44 | 26.16 kg/m^2 STANDARD_DEVIATION 3.52 | 25.38 kg/m^2 STANDARD_DEVIATION 4.09 | 25.55 kg/m^2 STANDARD_DEVIATION 3.33 | 28.31 kg/m^2 STANDARD_DEVIATION 4.58 | 26.46 kg/m^2 STANDARD_DEVIATION 3.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 7 Participants | 5 Participants | 7 Participants | 7 Participants | 6 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 3 Participants | 7 Participants | 4 Participants | 4 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 10 Participants |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 8 participants | 8 participants | 8 participants | 48 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 5 Participants | 5 Participants | 4 Participants | 4 Participants | 24 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 4 / 8 | 6 / 8 | 7 / 8 | 8 / 8 | 8 / 8 | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event
Adverse events include local and systemic reactions. All Grade 2 (moderate) adverse events were reported, regardless of relationship to study product. Number of participants with an AE are summarized by MedDRA system organ class (SOC). Each participant is only counted once per SOC.
Time frame: Day 1 through Day 11
Population: The safety population includes all participants who received any amount of study product (started first infusion).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AVYCAZ IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | General disorders and administration site conditions | 0 Participants |
| AVYCAZ IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Eye disorders | 0 Participants |
| AVYCAZ IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Cardiac Disorders | 1 Participants |
| AVYCAZ IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Infections and infestations | 0 Participants |
| AVYCAZ IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| AVYCAZ IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Investigations | 3 Participants |
| AVYCAZ IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Injury, poisoning and procedural complications | 0 Participants |
| AVYCAZ IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Nervous system disorders | 0 Participants |
| AVYCAZ CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Investigations | 1 Participants |
| AVYCAZ CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Injury, poisoning and procedural complications | 0 Participants |
| AVYCAZ CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Cardiac Disorders | 0 Participants |
| AVYCAZ CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Eye disorders | 0 Participants |
| AVYCAZ CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| AVYCAZ CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | General disorders and administration site conditions | 0 Participants |
| AVYCAZ CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Nervous system disorders | 0 Participants |
| AVYCAZ CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Infections and infestations | 0 Participants |
| ATM IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| ATM IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Investigations | 3 Participants |
| ATM IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Nervous system disorders | 1 Participants |
| ATM IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Eye disorders | 0 Participants |
| ATM IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Injury, poisoning and procedural complications | 0 Participants |
| ATM IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Cardiac Disorders | 0 Participants |
| ATM IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Infections and infestations | 1 Participants |
| ATM IV | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | General disorders and administration site conditions | 1 Participants |
| ATM CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Nervous system disorders | 1 Participants |
| ATM CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Cardiac Disorders | 1 Participants |
| ATM CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| ATM CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Eye disorders | 1 Participants |
| ATM CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | General disorders and administration site conditions | 0 Participants |
| ATM CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Infections and infestations | 0 Participants |
| ATM CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Injury, poisoning and procedural complications | 0 Participants |
| ATM CI | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Investigations | 5 Participants |
| AVYCAZ + ATM 1.5 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Infections and infestations | 0 Participants |
| AVYCAZ + ATM 1.5 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | General disorders and administration site conditions | 0 Participants |
| AVYCAZ + ATM 1.5 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Nervous system disorders | 0 Participants |
| AVYCAZ + ATM 1.5 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Investigations | 4 Participants |
| AVYCAZ + ATM 1.5 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Eye disorders | 0 Participants |
| AVYCAZ + ATM 1.5 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Cardiac Disorders | 1 Participants |
| AVYCAZ + ATM 1.5 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| AVYCAZ + ATM 1.5 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Injury, poisoning and procedural complications | 0 Participants |
| AVYCAZ + ATM 2.0 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| AVYCAZ + ATM 2.0 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Cardiac Disorders | 0 Participants |
| AVYCAZ + ATM 2.0 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | General disorders and administration site conditions | 0 Participants |
| AVYCAZ + ATM 2.0 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Infections and infestations | 0 Participants |
| AVYCAZ + ATM 2.0 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Injury, poisoning and procedural complications | 1 Participants |
| AVYCAZ + ATM 2.0 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Investigations | 4 Participants |
| AVYCAZ + ATM 2.0 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Nervous system disorders | 0 Participants |
| AVYCAZ + ATM 2.0 | Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event | Eye disorders | 0 Participants |
Secondary
Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC]
Mean and standard deviation (SD) of the RAUC PK parameter were estimated for ceftazidime, avibactam, and/or aztreonam by dividing the AUC(0-8) (avibactam and ceftazidime) or AUC(0-6) (aztreonam) on Day 7 by the AUC(0-Tau) on Day 1. AUC(0-8) and AUC(0-6) (µg\*hr/mL) on Day 7 and AUC(0-Tau) (µg\*hr/mL) on Day 1 were estimated from plasma concentration-time data using Non-compartmental analysis with the linear trapezoidal linear interpolation method for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0.
Time frame: Day 1 and Day 7
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. The AVYCAZ + ATM 1.5 arm consists of 4 participants as 4 participants missed aztreonam doses on day 7. The AVYCAZ CI and ATM CI arms consist of 0 participants as AUC(0-Tau) was not collected on Day 1 due to the study drug being administered as a continuous infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Avibactam | 0.87 Accumulation ratio | Standard Deviation 0.12 |
| AVYCAZ IV | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Ceftazidime | 0.98 Accumulation ratio | Standard Deviation 0.12 |
| ATM IV | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Aztreonam | 0.90 Accumulation ratio | Standard Deviation 0.07 |
| AVYCAZ + ATM 1.5 | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Aztreonam | 0.91 Accumulation ratio | Standard Deviation 0.04 |
| AVYCAZ + ATM 1.5 | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Ceftazidime | 0.95 Accumulation ratio | Standard Deviation 0.04 |
| AVYCAZ + ATM 1.5 | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Avibactam | 0.80 Accumulation ratio | Standard Deviation 0.03 |
| AVYCAZ + ATM 2.0 | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Ceftazidime | 0.95 Accumulation ratio | Standard Deviation 0.05 |
| AVYCAZ + ATM 2.0 | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Aztreonam | 0.94 Accumulation ratio | Standard Deviation 0.05 |
| AVYCAZ + ATM 2.0 | Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC] | Avibactam | 0.82 Accumulation ratio | Standard Deviation 0.06 |
Secondary
Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax)
Mean and standard deviation (SD) of the RCmax PK parameter were estimated for ceftazidime, avibactam, and/or aztreonam by dividing the Cmax on Day 7 by the Cmax on Day 1. Cmax (ug/mL) was estimated from plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0.
Time frame: Day 1 and Day 7
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. The AVYCAZ + ATM 1.5 arm consists of 4 participants as 4 participants missed aztreonam doses on day 7. The AVYCAZ CI and ATM CI arms consist of 0 participants as this data was not collected in arms where the study drug was administered as a continuous infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Ceftazidime | 0.96 Accumulation ratio | Standard Deviation 0.2 |
| AVYCAZ IV | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Avibactam | 0.88 Accumulation ratio | Standard Deviation 0.18 |
| ATM IV | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Aztreonam | 0.88 Accumulation ratio | Standard Deviation 0.07 |
| AVYCAZ + ATM 1.5 | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Ceftazidime | 0.96 Accumulation ratio | Standard Deviation 0.06 |
| AVYCAZ + ATM 1.5 | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Avibactam | 0.83 Accumulation ratio | Standard Deviation 0.05 |
| AVYCAZ + ATM 1.5 | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Aztreonam | 0.95 Accumulation ratio | Standard Deviation 0.05 |
| AVYCAZ + ATM 2.0 | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Avibactam | 0.91 Accumulation ratio | Standard Deviation 0.08 |
| AVYCAZ + ATM 2.0 | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Aztreonam | 0.97 Accumulation ratio | Standard Deviation 0.11 |
| AVYCAZ + ATM 2.0 | Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax) | Ceftazidime | 1.01 Accumulation ratio | Standard Deviation 0.11 |
Secondary
Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)]
Mean and standard deviation (SD) of the AUC(0-Tau) (µg\*hr/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis using linear trapezoidal linear interpolation method for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. AVYCAZ CI and ATM CI were not reported.
Time frame: Day 1
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. The AVYCAZ CI and ATM CI arms consist of 0 participants as AUC(0-Tau) was not collected on Day 1 due to the study drug being administered as a continuous infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Avibactam | 35.80 µg*hr/mL | Standard Deviation 5.96 |
| AVYCAZ IV | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Ceftazidime | 223.00 µg*hr/mL | Standard Deviation 33.9 |
| ATM IV | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Aztreonam | 266.00 µg*hr/mL | Standard Deviation 36.1 |
| AVYCAZ + ATM 1.5 | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Avibactam | 44.00 µg*hr/mL | Standard Deviation 7.1 |
| AVYCAZ + ATM 1.5 | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Ceftazidime | 255.00 µg*hr/mL | Standard Deviation 34.3 |
| AVYCAZ + ATM 1.5 | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Aztreonam | 221.00 µg*hr/mL | Standard Deviation 32.7 |
| AVYCAZ + ATM 2.0 | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Avibactam | 42.40 µg*hr/mL | Standard Deviation 7.16 |
| AVYCAZ + ATM 2.0 | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Aztreonam | 295.00 µg*hr/mL | Standard Deviation 41.3 |
| AVYCAZ + ATM 2.0 | Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)] | Ceftazidime | 241.00 µg*hr/mL | Standard Deviation 33.1 |
Secondary
Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)]
Mean and standard deviation (SD) of the AUC(0-inf) (µg\*hr/mL) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Time frame: Day 7
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. Participants in the ATM CI arm do not have data because dosing for all participants was stopped prior to Day 7, so their PK data was excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Ceftazidime | 235.00 µg*hr/mL | Standard Deviation 25.8 |
| AVYCAZ IV | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Avibactam | 32.10 µg*hr/mL | Standard Deviation 3.73 |
| AVYCAZ CI | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Avibactam | 42.40 µg*hr/mL | Standard Deviation 7.17 |
| AVYCAZ CI | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Ceftazidime | 308.00 µg*hr/mL | Standard Deviation 63.3 |
| ATM IV | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Aztreonam | 263.00 µg*hr/mL | Standard Deviation 38.8 |
| AVYCAZ + ATM 1.5 | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Avibactam | 39.10 µg*hr/mL | Standard Deviation 4.57 |
| AVYCAZ + ATM 1.5 | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Ceftazidime | 277.00 µg*hr/mL | Standard Deviation 27.5 |
| AVYCAZ + ATM 1.5 | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Aztreonam | 245.00 µg*hr/mL | Standard Deviation 23.5 |
| AVYCAZ + ATM 2.0 | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Aztreonam | 317.00 µg*hr/mL | Standard Deviation 47.7 |
| AVYCAZ + ATM 2.0 | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Ceftazidime | 249.00 µg*hr/mL | Standard Deviation 26.4 |
| AVYCAZ + ATM 2.0 | Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)] | Avibactam | 36.10 µg*hr/mL | Standard Deviation 6.17 |
Secondary
Concentration of Study Drug at Steady State After Continuous Infusion (Css)
Mean and standard deviation (SD) of the Css (ug/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data for AVYCAZ CI and ATM CI.
Time frame: Day 1
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ CI | Concentration of Study Drug at Steady State After Continuous Infusion (Css) | Avibactam | 4.34 ug/mL | Standard Deviation 1.8 |
| AVYCAZ CI | Concentration of Study Drug at Steady State After Continuous Infusion (Css) | Ceftazidime | 27.60 ug/mL | Standard Deviation 11.4 |
| ATM CI | Concentration of Study Drug at Steady State After Continuous Infusion (Css) | Aztreonam | 58.80 ug/mL | Standard Deviation 6.05 |
Secondary
Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level
Number of participants with an AE are summarized by MedDRA system organ class (SOC) and severity. Each participant is only counted once at the highest severity recorded. For clinical laboratory tests, mild abnormal laboratory values that were not, in the investigator's opinion, medically significant were not reported as adverse events.
Time frame: Day 1 through Day 14
Population: The safety population includes all participants who received any amount of study product (started first infusion).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Mild | 2 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | None | 5 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Mild | 2 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Mild | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Mild | 1 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Mild | 1 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Mild | 3 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | None | 8 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | None | 7 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | None | 7 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | None | 4 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | None | 7 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Mild | 1 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Moderate | 2 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Mild | 1 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | None | 8 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | None | 8 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Severe | 1 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Mild | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Mild | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Mild | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | None | 8 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | None | 8 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Moderate | 1 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Mild | 1 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Mild | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | None | 7 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Moderate | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | None | 6 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Severe | 0 Participants |
| AVYCAZ IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | None | 5 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | None | 6 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | None | 7 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Mild | 1 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Mild | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Mild | 2 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | None | 8 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Mild | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | None | 7 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Mild | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | None | 8 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Mild | 1 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Mild | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | None | 7 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Mild | 2 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | None | 7 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | None | 6 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | None | 8 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Mild | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | None | 8 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Mild | 4 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Moderate | 1 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | None | 3 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Mild | 1 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Mild | 1 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | None | 7 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Mild | 1 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Severe | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | None | 8 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Moderate | 0 Participants |
| AVYCAZ CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Severe | 1 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Mild | 4 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Mild | 3 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Mild | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Moderate | 1 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | None | 6 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Mild | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | None | 7 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Moderate | 2 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | None | 7 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Mild | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | None | 4 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | None | 8 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | None | 2 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Moderate | 1 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | None | 8 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Mild | 3 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Mild | 2 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Moderate | 1 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Mild | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Mild | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Moderate | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | None | 8 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | None | 4 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Mild | 1 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | None | 6 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | None | 5 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Mild | 2 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | None | 8 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Severe | 0 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Mild | 1 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Mild | 3 Participants |
| ATM IV | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | None | 6 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Mild | 2 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Severe | 1 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | None | 6 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | None | 8 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Mild | 1 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | None | 8 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Moderate | 1 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | None | 8 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | None | 8 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Mild | 2 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Severe | 2 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | None | 7 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Moderate | 3 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Moderate | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Moderate | 1 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | None | 8 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | None | 7 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | None | 1 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | None | 8 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | None | 6 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Severe | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | None | 8 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | None | 8 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Mild | 0 Participants |
| ATM CI | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Mild | 3 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | None | 8 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Mild | 3 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | None | 4 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Mild | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | None | 8 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Mild | 5 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | None | 3 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | None | 5 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Mild | 1 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | None | 7 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Mild | 1 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | None | 7 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Mild | 4 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Moderate | 3 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Severe | 1 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | None | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Mild | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Mild | 2 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | None | 6 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Mild | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Moderate | 1 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | None | 8 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Mild | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Moderate | 1 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | None | 7 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Mild | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | None | 8 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Mild | 1 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Severe | 0 Participants |
| AVYCAZ + ATM 1.5 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | None | 7 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Mild | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | None | 8 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | None | 8 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Musculoskeletal and connective tissue disorders | Mild | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | None | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | None | 6 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Mild | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Moderate | 4 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Investigations | Mild | 4 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Moderate | 1 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | Mild | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | None | 8 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Infections and infestations | Mild | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Mild | 4 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | None | 4 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | General disorders and administration site conditions | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | None | 5 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Skin and subcutaneous tissue disorders | None | 8 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Mild | 3 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | None | 8 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Gastrointestinal Disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Mild | 2 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Eye disorders | Mild | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | None | 6 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Vascular disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Cardiac Disorders | Mild | 2 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Mild | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | None | 7 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Moderate | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Renal and urinary disorders | Mild | 1 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | None | 8 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Injury, poisoning and procedural complications | None | 7 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Respiratory, thoracic and mediastinal disorders | Severe | 0 Participants |
| AVYCAZ + ATM 2.0 | Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level | Nervous system disorders | Severe | 0 Participants |
Secondary
Maximum Plasma Concentration of Study Drug After the First Dose (Cmax)
Mean and standard deviation (SD) of the Cmax (ug/mL) PK parameter after the first dose were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Time frame: Day 1
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Avibactam | 12.40 ug/mL | Standard Deviation 2.38 |
| AVYCAZ IV | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Ceftazidime | 67.90 ug/mL | Standard Deviation 14 |
| AVYCAZ CI | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Avibactam | 13.10 ug/mL | Standard Deviation 2.2 |
| AVYCAZ CI | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Ceftazidime | 71.20 ug/mL | Standard Deviation 11.8 |
| ATM IV | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Aztreonam | 89.10 ug/mL | Standard Deviation 10.4 |
| ATM CI | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Aztreonam | 93.80 ug/mL | Standard Deviation 4.98 |
| AVYCAZ + ATM 1.5 | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Ceftazidime | 82.70 ug/mL | Standard Deviation 18.5 |
| AVYCAZ + ATM 1.5 | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Avibactam | 15.80 ug/mL | Standard Deviation 3.04 |
| AVYCAZ + ATM 1.5 | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Aztreonam | 71.20 ug/mL | Standard Deviation 12.8 |
| AVYCAZ + ATM 2.0 | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Avibactam | 14.30 ug/mL | Standard Deviation 2.69 |
| AVYCAZ + ATM 2.0 | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Aztreonam | 93.20 ug/mL | Standard Deviation 15.8 |
| AVYCAZ + ATM 2.0 | Maximum Plasma Concentration of Study Drug After the First Dose (Cmax) | Ceftazidime | 70.30 ug/mL | Standard Deviation 12.7 |
Secondary
Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax)
Mean and standard deviation (SD) of the Cmax (ug/mL) PK parameter following multiple daily dosing were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Time frame: Day 7
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. Participants in the ATM CI arm do not have data because dosing for all participants was stopped prior to Day 7, so their PK data was excluded from the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Avibactam | 10.70 ug/mL | Standard Deviation 2.52 |
| AVYCAZ IV | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Ceftazidime | 63.60 ug/mL | Standard Deviation 12.6 |
| AVYCAZ CI | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Ceftazidime | 31.80 ug/mL | Standard Deviation 6.31 |
| AVYCAZ CI | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Avibactam | 4.58 ug/mL | Standard Deviation 0.74 |
| ATM IV | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Aztreonam | 78.40 ug/mL | Standard Deviation 9.38 |
| AVYCAZ + ATM 1.5 | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Avibactam | 14.20 ug/mL | Standard Deviation 1.75 |
| AVYCAZ + ATM 1.5 | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Aztreonam | 74.40 ug/mL | Standard Deviation 9.14 |
| AVYCAZ + ATM 1.5 | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Ceftazidime | 88.20 ug/mL | Standard Deviation 12.4 |
| AVYCAZ + ATM 2.0 | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Aztreonam | 90.30 ug/mL | Standard Deviation 16.7 |
| AVYCAZ + ATM 2.0 | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Avibactam | 12.80 ug/mL | Standard Deviation 2.03 |
| AVYCAZ + ATM 2.0 | Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax) | Ceftazidime | 69.80 ug/mL | Standard Deviation 8.31 |
Secondary
Minimum Plasma Concentration of Study Drug at the End of the Dosing Interval on Day 7 (Cmin)
Mean and standard deviation (SD) of the Cmin (ug/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. Cmin was not provided on day 7 because it was the last dosage of the study product administered; Cmin was therefore not calculated for this terminal elimination profile since the minimum concentration after a final dose would only reflect the last time point after Cmax that a blood sample is obtained, or the assay's limit of quantitation. It is therefore not comparable to Cmin calculated on prior days.
Time frame: Day 7
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. Zero participants have data because this analysis was not performed.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Minimum Plasma Concentration of Study Drug at the End of the Dosing Interval on Day 7 (Cmin) | Avibactam | — |
| Unknown | Minimum Plasma Concentration of Study Drug at the End of the Dosing Interval on Day 7 (Cmin) | Ceftazidime | — |
| Unknown | Minimum Plasma Concentration of Study Drug at the End of the Dosing Interval on Day 7 (Cmin) | Aztreonam | — |
Secondary
Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin)
Mean and standard deviation (SD) of the Cmin (ug/mL) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0.
Time frame: Day 1
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. The AVYCAZ CI and ATM CI arms consist of 0 participants as this data was not collected in arms where the study drug was administered as a continuous infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Ceftazidime | 5.52 ug/mL | Standard Deviation 1.2 |
| AVYCAZ IV | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Avibactam | 0.52 ug/mL | Standard Deviation 0.2 |
| ATM IV | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Aztreonam | 13.90 ug/mL | Standard Deviation 2.84 |
| AVYCAZ + ATM 1.5 | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Aztreonam | 13.30 ug/mL | Standard Deviation 1.91 |
| AVYCAZ + ATM 1.5 | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Avibactam | 0.74 ug/mL | Standard Deviation 0.4 |
| AVYCAZ + ATM 1.5 | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Ceftazidime | 6.29 ug/mL | Standard Deviation 2.58 |
| AVYCAZ + ATM 2.0 | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Ceftazidime | 6.28 ug/mL | Standard Deviation 1.54 |
| AVYCAZ + ATM 2.0 | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Avibactam | 0.72 ug/mL | Standard Deviation 0.29 |
| AVYCAZ + ATM 2.0 | Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin) | Aztreonam | 18.90 ug/mL | Standard Deviation 3.99 |
Secondary
Renal Clearance of Study Drug (CLR)
Mean and standard deviation (SD) of the CLR (L/h) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma and urine concentration-time data using Non-compartmental analysis. Renal clearance was calculated as Ae(0-8)/AUC(0-8) for ceftazidime and avibactam and as AE(0-4)/AUC(0-4) for aztreonam where Ae(0-8) and Ae(0-4) are the amounts of study drug excreted into the urine from time of dosing to 8 or 4 h post-dose, respectively, and AUC(0-8) and AUC(0-4) are the areas under the plasma concentration-time curve from time of dosing to 8 or 4 h post-dose, respectively.
Time frame: Day 1
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. The AVYCAZ CI and AVYCAZ + ATM 2.0 arms consist of 7 participants due to participants missing the urine collection interval.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Renal Clearance of Study Drug (CLR) | Avibactam | 11.10 L/h | Standard Deviation 2.58 |
| AVYCAZ IV | Renal Clearance of Study Drug (CLR) | Ceftazidime | 5.70 L/h | Standard Deviation 1.23 |
| AVYCAZ CI | Renal Clearance of Study Drug (CLR) | Avibactam | 11.70 L/h | Standard Deviation 2.61 |
| AVYCAZ CI | Renal Clearance of Study Drug (CLR) | Ceftazidime | 6.92 L/h | Standard Deviation 1.71 |
| ATM IV | Renal Clearance of Study Drug (CLR) | Aztreonam | 4.25 L/h | Standard Deviation 0.91 |
| ATM CI | Renal Clearance of Study Drug (CLR) | Aztreonam | 3.90 L/h | Standard Deviation 0.97 |
| AVYCAZ + ATM 1.5 | Renal Clearance of Study Drug (CLR) | Ceftazidime | 7.10 L/h | Standard Deviation 1.09 |
| AVYCAZ + ATM 1.5 | Renal Clearance of Study Drug (CLR) | Avibactam | 11.40 L/h | Standard Deviation 2.36 |
| AVYCAZ + ATM 1.5 | Renal Clearance of Study Drug (CLR) | Aztreonam | 4.61 L/h | Standard Deviation 1.66 |
| AVYCAZ + ATM 2.0 | Renal Clearance of Study Drug (CLR) | Avibactam | 14.70 L/h | Standard Deviation 5.35 |
| AVYCAZ + ATM 2.0 | Renal Clearance of Study Drug (CLR) | Aztreonam | 4.50 L/h | Standard Deviation 1.08 |
| AVYCAZ + ATM 2.0 | Renal Clearance of Study Drug (CLR) | Ceftazidime | 9.42 L/h | Standard Deviation 3 |
Secondary
Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax)
Mean and standard deviation (SD) of the Tmax (h) PK parameter after the first dose were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Time frame: Day 1
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Avibactam | 1.89 h | Standard Deviation 0.35 |
| AVYCAZ IV | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Ceftazidime | 2.06 h | Standard Deviation 0.42 |
| AVYCAZ CI | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Avibactam | 2.00 h | Standard Deviation 0 |
| AVYCAZ CI | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Ceftazidime | 2.06 h | Standard Deviation 0.18 |
| ATM IV | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Aztreonam | 1.94 h | Standard Deviation 0.18 |
| ATM CI | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Aztreonam | 2.00 h | Standard Deviation 0.01 |
| AVYCAZ + ATM 1.5 | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Ceftazidime | 1.93 h | Standard Deviation 0.33 |
| AVYCAZ + ATM 1.5 | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Avibactam | 1.81 h | Standard Deviation 0.27 |
| AVYCAZ + ATM 1.5 | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Aztreonam | 1.99 h | Standard Deviation 0.02 |
| AVYCAZ + ATM 2.0 | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Avibactam | 1.99 h | Standard Deviation 0.01 |
| AVYCAZ + ATM 2.0 | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Aztreonam | 2.06 h | Standard Deviation 0.18 |
| AVYCAZ + ATM 2.0 | Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax) | Ceftazidime | 1.93 h | Standard Deviation 0.18 |
Secondary
Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax)
Mean and standard deviation (SD) of the Tmax (h) PK parameter following multiple daily dosing were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Time frame: Day 7
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. Participants in the ATM CI arm do not have data because dosing for all participants was stopped prior to Day 7, so their PK data was excluded from the analysis. The AVYCAZ + ATM 1.5 arm consists of 4 participants as 4 participants missed aztreonam doses on day 7.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Avibactam | 1.82 h | Standard Deviation 0.27 |
| AVYCAZ IV | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Ceftazidime | 2.14 h | Standard Deviation 0.35 |
| AVYCAZ CI | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Ceftazidime | 2.25 h | Standard Deviation 2.06 |
| AVYCAZ CI | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Avibactam | 2.85 h | Standard Deviation 2.59 |
| ATM IV | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Aztreonam | 2.00 h | Standard Deviation 0 |
| AVYCAZ + ATM 1.5 | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Aztreonam | 1.99 h | Standard Deviation 0.02 |
| AVYCAZ + ATM 1.5 | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Ceftazidime | 1.86 h | Standard Deviation 0.25 |
| AVYCAZ + ATM 1.5 | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Avibactam | 1.99 h | Standard Deviation 0.02 |
| AVYCAZ + ATM 2.0 | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Ceftazidime | 1.88 h | Standard Deviation 0.23 |
| AVYCAZ + ATM 2.0 | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Avibactam | 1.88 h | Standard Deviation 0.23 |
| AVYCAZ + ATM 2.0 | Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax) | Aztreonam | 2.00 h | Standard Deviation 0.04 |
Secondary
Total Body Plasma Clearance of Study Drug (CL)
Mean and standard deviation (SD) of the CL (L/h) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Time frame: Day 7
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. The ATM CI arm consists of 0 participants as dosing for all was stopped prior to Day 7. The AVYCAZ + ATM 1.5 arm consists of 4 participants as they missed doses on day 7. One participant in AVYCAZ CI for avibactam had an elimination parameter that did not meet acceptance criteria and was excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Total Body Plasma Clearance of Study Drug (CL) | Avibactam | 15.80 L/h | Standard Deviation 1.85 |
| AVYCAZ IV | Total Body Plasma Clearance of Study Drug (CL) | Ceftazidime | 8.59 L/h | Standard Deviation 0.95 |
| AVYCAZ CI | Total Body Plasma Clearance of Study Drug (CL) | Ceftazidime | 6.80 L/h | Standard Deviation 1.59 |
| AVYCAZ CI | Total Body Plasma Clearance of Study Drug (CL) | Avibactam | 12.20 L/h | Standard Deviation 2.38 |
| ATM IV | Total Body Plasma Clearance of Study Drug (CL) | Aztreonam | 7.74 L/h | Standard Deviation 1.07 |
| AVYCAZ + ATM 1.5 | Total Body Plasma Clearance of Study Drug (CL) | Aztreonam | 6.18 L/h | Standard Deviation 0.57 |
| AVYCAZ + ATM 1.5 | Total Body Plasma Clearance of Study Drug (CL) | Ceftazidime | 7.26 L/h | Standard Deviation 0.68 |
| AVYCAZ + ATM 1.5 | Total Body Plasma Clearance of Study Drug (CL) | Avibactam | 12.90 L/h | Standard Deviation 1.59 |
| AVYCAZ + ATM 2.0 | Total Body Plasma Clearance of Study Drug (CL) | Ceftazidime | 8.13 L/h | Standard Deviation 1.01 |
| AVYCAZ + ATM 2.0 | Total Body Plasma Clearance of Study Drug (CL) | Avibactam | 14.30 L/h | Standard Deviation 2.85 |
| AVYCAZ + ATM 2.0 | Total Body Plasma Clearance of Study Drug (CL) | Aztreonam | 6.47 L/h | Standard Deviation 1.2 |
Secondary
Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss)
Mean and standard deviation (SD) of the Vss (L) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Time frame: Day 7
Population: The PK population includes all participants who received at least one dose of study drug and had at least one quantifiable plasma or urine concentration of ceftazidime, avibactam, or aztreonam. The ATM CI arm consists of 0 participants as dosing for all was stopped prior to Day 7. The AVYCAZ + ATM 1.5 arm consists of 4 participants as they missed doses on day 7. One participant in AVYCAZ CI for avibactam had an elimination parameter that did not meet acceptance criteria and was excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVYCAZ IV | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Avibactam | 25.90 L | Standard Deviation 5.26 |
| AVYCAZ IV | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Ceftazidime | 19.90 L | Standard Deviation 3.86 |
| AVYCAZ CI | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Ceftazidime | 12.60 L | Standard Deviation 3.17 |
| AVYCAZ CI | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Avibactam | 17.40 L | Standard Deviation 4.91 |
| ATM IV | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Aztreonam | 14.30 L | Standard Deviation 1.86 |
| AVYCAZ + ATM 1.5 | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Avibactam | 18.50 L | Standard Deviation 4.48 |
| AVYCAZ + ATM 1.5 | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Ceftazidime | 14.50 L | Standard Deviation 2.86 |
| AVYCAZ + ATM 1.5 | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Aztreonam | 11.50 L | Standard Deviation 2.14 |
| AVYCAZ + ATM 2.0 | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Avibactam | 24.30 L | Standard Deviation 6.65 |
| AVYCAZ + ATM 2.0 | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Aztreonam | 13.80 L | Standard Deviation 3.17 |
| AVYCAZ + ATM 2.0 | Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss) | Ceftazidime | 19.20 L | Standard Deviation 4.27 |