Trial Outcomes & Findings for Safety Study of Intravenous Ertapenem in Combination With Zidebactam (WCK 6777) (NCT NCT05645757)
NCT ID: NCT05645757
Last Updated: 2025-01-20
Results Overview
Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). Number of participants with a TEAE are summarized by dose group and by MedDRA System Organ Class (SOC).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
54 participants
Primary outcome timeframe
Day 1 through Day 11
Results posted on
2025-01-20
Participant Flow
Participants were recruited between 19APR2023 and 24OCT2023 by the clinical trials unit (CTU) utilizing the CTU subject database and IRB-approved advertisements and social media.
Participant milestones
| Measure |
Cohort 1 - WCK 6777 2 g
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Cohort 2 - ERT 2 g
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
|
Cohort 3 - ZID 2 g
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
|
Cohort 4 - WCK 6777 4 g
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Cohort 5 - ERT 3 g
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
|
Cohort 6 - ZID 3 g
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
|
Cohort 7 - WCK 6777 6 g
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
7
|
7
|
6
|
10
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1 - WCK 6777 2 g
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Cohort 2 - ERT 2 g
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
|
Cohort 3 - ZID 2 g
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
|
Cohort 4 - WCK 6777 4 g
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Cohort 5 - ERT 3 g
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
|
Cohort 6 - ZID 3 g
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
|
Cohort 7 - WCK 6777 6 g
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
Enrolled but treatment not administered
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
0
|
Baseline Characteristics
Safety Study of Intravenous Ertapenem in Combination With Zidebactam (WCK 6777)
Baseline characteristics by cohort
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Cohort 5 - ERT 3 g
n=7 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
|
Cohort 6 - ZID 3 g
n=7 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
Ertapenem: A 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics
Zidebactam: A ß-lactamase inhibitor and ß-lactam enhancer from the diazabicyclooctane (DBO) class
WCK 6777: A combination of ertapenem (ERT) and zidebactam (ZID)
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
Total
n=54 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
33.7 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
35.2 years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
32.3 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
33.2 years
STANDARD_DEVIATION 7.0 • n=4 Participants
|
33.6 years
STANDARD_DEVIATION 7.9 • n=21 Participants
|
37.3 years
STANDARD_DEVIATION 5.6 • n=8 Participants
|
29.2 years
STANDARD_DEVIATION 9.0 • n=8 Participants
|
30.7 years
STANDARD_DEVIATION 6.7 • n=24 Participants
|
33.0 years
STANDARD_DEVIATION 7.6 • n=42 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
4 Participants
n=24 Participants
|
20 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
6 Participants
n=24 Participants
|
34 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
8 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
9 Participants
n=24 Participants
|
46 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
7 Participants
n=24 Participants
|
28 Participants
n=42 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
23 Participants
n=42 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
|
BMI
|
27.08 kg/m2
STANDARD_DEVIATION 2.93 • n=5 Participants
|
28.57 kg/m2
STANDARD_DEVIATION 2.05 • n=7 Participants
|
25.18 kg/m2
STANDARD_DEVIATION 3.38 • n=5 Participants
|
27.63 kg/m2
STANDARD_DEVIATION 2.85 • n=4 Participants
|
23.83 kg/m2
STANDARD_DEVIATION 1.62 • n=21 Participants
|
27.27 kg/m2
STANDARD_DEVIATION 2.76 • n=8 Participants
|
24.05 kg/m2
STANDARD_DEVIATION 4.36 • n=8 Participants
|
26.87 kg/m2
STANDARD_DEVIATION 2.82 • n=24 Participants
|
26.32 kg/m2
STANDARD_DEVIATION 3.15 • n=42 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). Number of participants with a TEAE are summarized by dose group and by MedDRA System Organ Class (SOC).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events
Blood and lymphatic system disorders
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Gastrointestinal disorders
|
2 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
General disorders and administration site conditions
|
3 Participants
|
5 Participants
|
5 Participants
|
4 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
6 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Musculoskeletal and connective tissue disorders
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Nervous system disorders
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Infections and infestations
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Injury, poisoning and procedural complications
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Investigations
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Renal and urinary disorders
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Respiratory, thoracic and mediastinal disorders
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events
Skin and subcutaneous tissue disorders
|
1 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). Number of TEAEs reported are summarized by dose group and MedDRA System Organ Class (SOC)..
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Treatment-Emergent Adverse Events Reported
General disorders and administration site conditions
|
6 events
|
11 events
|
8 events
|
6 events
|
6 events
|
3 events
|
6 events
|
14 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Skin and subcutaneous tissue disorders
|
1 events
|
0 events
|
3 events
|
0 events
|
0 events
|
0 events
|
0 events
|
1 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Blood and lymphatic system disorders
|
0 events
|
1 events
|
1 events
|
0 events
|
0 events
|
0 events
|
1 events
|
1 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Gastrointestinal disorders
|
3 events
|
2 events
|
0 events
|
1 events
|
1 events
|
0 events
|
1 events
|
1 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Infections and infestations
|
0 events
|
1 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Injury, poisoning and procedural complications
|
1 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Investigations
|
1 events
|
0 events
|
1 events
|
1 events
|
2 events
|
0 events
|
1 events
|
3 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Musculoskeletal and connective tissue disorders
|
1 events
|
0 events
|
0 events
|
0 events
|
0 events
|
1 events
|
0 events
|
0 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Nervous system disorders
|
1 events
|
1 events
|
1 events
|
0 events
|
1 events
|
0 events
|
0 events
|
2 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Renal and urinary disorders
|
0 events
|
1 events
|
0 events
|
1 events
|
0 events
|
0 events
|
0 events
|
0 events
|
|
Number of Treatment-Emergent Adverse Events Reported
Respiratory, thoracic and mediastinal disorders
|
0 events
|
0 events
|
1 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
Adverse events (AEs) are defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, regardless of its causal relationship to the product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of the product, and are described as treatment-emergent AEs (TEAEs). TEAEs are assessed by the investigator to determine relationship to the study drug. Number of participants with a related TEAE are summarized by dose group and by MedDRA System Organ Class (SOC).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Blood and lymphatic system disorders
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Gastrointestinal disorders
|
2 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
General disorders and administration site conditions
|
3 Participants
|
5 Participants
|
4 Participants
|
3 Participants
|
2 Participants
|
2 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Injury, poisoning and procedural complications
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Investigations
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Musculoskeletal and connective tissue disorders
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Nervous system disorders
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Renal and urinary disorders
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Respiratory, thoracic and mediastinal disorders
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Skin and subcutaneous tissue disorders
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events Related to Study Product
Infections and infestations
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
Serious AEs (SAEs) meet one or more of the following criteria: death, life-threatening AEs, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, substantial disruption of the ability to conduct normal life function, congenital anomaly/birth defect, or important medical events that may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. SAEs are listed.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Serious Adverse Events Reported
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
0 events
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
Parameters and thresholds include alanine aminotransferase =33 (female (F) 19Y), =30 (F \>19) or =47 U/L (male (M) =19Y); albumin =3.5 g/dL; alkaline phosphatase =129 (F 19Y), =126 (F =49Y), =170 (M 19Y) or =131 U/L (M =49Y); aspartate aminotransferase =33 (19Y) or =41 U/L (20-49Y); bilirubin =1.2 (19Y) or =1.3 mg/dL (\>19Y); calcium =8.8 (4-19Y), =8.5 (20-49Y), =10.5 (4-19Y), =10.3 (F 20-49Y) or =10.4 mg/dL (M 20-49Y); carbon dioxide =19 or =33 mmol/L; creatinine =0.97 (F 18-29Y), =0.98 (F 30-39Y), =1.00 (F 40-49Y), =1.25 (M 18-29Y), =1.27 (M 30-39Y) or =1.30 mg/dL (M 40-49Y); direct bilirubin =0.3 mg/dL; glucose =64 or =100 mg/dL; potassium =3.7 (19Y), =3.4 (\>19Y), = 5.2 (19Y) or = 5.4 mmol/L (\>19Y); protein =6.2 (19Y) or =6.0 g/dL (\>19Y); sodium =134 or =147 mmol/L; and urea nitrogen =21 (19Y) or =26 mg/dL (\>19Y). All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Alanine aminotransferase increase
|
0 Participants
|
2 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Albumin decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Alkaline phosphatase increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Aspartate aminotransferase increase
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Calcium decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Calcium increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Carbon dioxide decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Creatinine increase
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Direct bilirubin increase
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Glucose decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Potassium increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Protein decrease
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Sodium decrease
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Sodium increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Bilirubin increase
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Carbon dioxide increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Glucose increase
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Potassium decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results
Urea nitrogen increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
Parameters and thresholds include basophils =201 x106/L (\>6Y); eosinophils =501 x106/L (\>6Y); hemoglobin =11.4 (female (F) 18Y), =11.6 (F \>18Y), =11.9 (male (M) 18Y) or =13.1 g/dL (M \>18Y); leukocytes =4.4 (18Y), =3.7 (\>18Y), =13.1 (18Y) or =10.9 x109/L (\>18Y); lymphocytes =1199 (18Y) or =849 x106/L (\>18Y); monocytes =901 (18Y) or =951 x106/L (\>18Y); neutrophils =1799 (18Y) or =1499 x106/L (\>18Y); and platelets \<140 x109/L. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Hemoglobin decrease
|
3 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Basophils increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Eosinophils increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Leukocytes decrease
|
3 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Leukocytes increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Lymphocytes decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Monocytes increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Neutrophils decrease
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology Laboratory Toxicity Results
Platelets decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
Parameters and thresholds include activated partial thromboplastin time \>32 s, prothrombin intl. normalized ratio \>1.1 (ratio), and prothrombin time \>11.5 s. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Coagulation Laboratory Toxicity Results
Activated partial thromboplastin time increase
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Coagulation Laboratory Toxicity Results
Prothrombin intl. normalized ratio (INR) increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Coagulation Laboratory Toxicity Results
Prothrombin time increase
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
Parameters and thresholds include dipstick measurements of glucose =1+, leukocyte esterase =1+, occult blood =1+, protein =1+ and urinalysis with microscopy results of at least a few bacteria, red blood cells (RBC) =3 per high-powered field (HPF), and white blood cells (WBC) =6 per HPF. If dipstick results were abnormal, urinalysis with microscopy was performed. All abnormal toxicity results are included, but Grade 1 values at screening/baseline allowed for enrollment were only considered TEAEs if they increased in severity.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results
WBC increase
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results
Bacteria increase
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results
Glucose increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results
Leukocyte esterase increase
|
1 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results
Occult blood increase
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results
Protein increase
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results
RBC increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 8 and Day 11Population: Safety Population: All participants that received any amount of study drug(s).
The only ECG parameters graded were PR interval with a threshold of =211 msec and QTcF interval with a threshold of =471 msec (female) or =451 msec (male) or an increase of =30 msec above baseline. ECG values after dosing were considered as TEAEs if they met toxicity grading criteria.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results
PR interval
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results
QTcF interval
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 11Population: Safety Population: All participants that received any amount of study drug(s).
VS parameters and thresholds include diastolic blood pressure =90 mmHg, oral temperature =37.3 °C, pulse =49 or =101 beats/min, respiratory rate =21 breaths/min, and systolic blood pressure =88 or =131 mmHg. VS could be repeated up to twice more at rest and within at least 5 minutes of each other. The following rules were used to determine which vital sign measurement to use for analysis if repeat measurements occurred: 1. If the first replicate was normal, it was used. 2. If the first and second replicates were both abnormal, the replicate with the higher severity was used. 3. If the first replicate was abnormal, the second replicate was normal, and the third replicate was not performed, the first replicate was used. 4. If the first replicate was abnormal and the second and third replicates were normal, the second replicate was used. 5. If the first and third replicates were abnormal and the second replicate was normal, the abnormal replicate with the higher severity was used.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 Participants
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Vital Signs (VS)
Diastolic blood pressure increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs (VS)
Oral temperature increase
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Vital Signs (VS)
Pulse decrease
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs (VS)
Systolic blood pressure increase
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Signs (VS)
Pulse increase
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Signs (VS)
Respiratory rate increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs (VS)
Systolic blood pressure decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmax (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
196.66 µg/mL
Geometric Coefficient of Variation 14
|
303.43 µg/mL
Geometric Coefficient of Variation 9
|
—
|
354.41 µg/mL
Geometric Coefficient of Variation 8
|
378.71 µg/mL
Geometric Coefficient of Variation 10
|
—
|
391.87 µg/mL
Geometric Coefficient of Variation 13
|
—
|
|
Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
16.60 µg/mL
Geometric Coefficient of Variation 17
|
34.00 µg/mL
Geometric Coefficient of Variation 17
|
—
|
42.10 µg/mL
Geometric Coefficient of Variation 22
|
58.45 µg/mL
Geometric Coefficient of Variation 17
|
—
|
59.42 µg/mL
Geometric Coefficient of Variation 19
|
—
|
|
Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
69.67 µg/mL
Geometric Coefficient of Variation 15
|
—
|
120.41 µg/mL
Geometric Coefficient of Variation 22
|
133.51 µg/mL
Geometric Coefficient of Variation 16
|
—
|
111.71 µg/mL
Geometric Coefficient of Variation 10
|
128.42 µg/mL
Geometric Coefficient of Variation 11
|
—
|
|
Maximum Observed Concentration (Cmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
64.35 µg/mL
Geometric Coefficient of Variation 20
|
—
|
105.42 µg/mL
Geometric Coefficient of Variation 16
|
98.41 µg/mL
Geometric Coefficient of Variation 55
|
—
|
108.79 µg/mL
Geometric Coefficient of Variation 11
|
124.99 µg/mL
Geometric Coefficient of Variation 10
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmin (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
2.15 µg/mL
Geometric Coefficient of Variation 50
|
2.61 µg/mL
Geometric Coefficient of Variation 107
|
—
|
3.10 µg/mL
Geometric Coefficient of Variation 60
|
7.32 µg/mL
Geometric Coefficient of Variation 14
|
—
|
5.91 µg/mL
Geometric Coefficient of Variation 33
|
—
|
|
Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.10 µg/mL
Geometric Coefficient of Variation 40
|
0.16 µg/mL
Geometric Coefficient of Variation 42
|
—
|
0.14 µg/mL
Geometric Coefficient of Variation 67
|
0.36 µg/mL
Geometric Coefficient of Variation 24
|
—
|
0.28 µg/mL
Geometric Coefficient of Variation 35
|
—
|
|
Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.09 µg/mL
Geometric Coefficient of Variation 37
|
—
|
0.11 µg/mL
Geometric Coefficient of Variation 72
|
0.10 µg/mL
Geometric Coefficient of Variation 44
|
—
|
0.13 µg/mL
Geometric Coefficient of Variation 28
|
0.15 µg/mL
Geometric Coefficient of Variation 30
|
—
|
|
Minimum Observed Concentration (Cmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.09 µg/mL
Geometric Coefficient of Variation 22
|
—
|
0.07 µg/mL
Geometric Coefficient of Variation 36
|
0.10 µg/mL
Geometric Coefficient of Variation 39
|
—
|
0.14 µg/mL
Geometric Coefficient of Variation 26
|
0.14 µg/mL
Geometric Coefficient of Variation 34
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Ctau (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group. Ctau is estimated using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
2.02 µg/mL
Geometric Coefficient of Variation 50
|
2.29 µg/mL
Geometric Coefficient of Variation 112
|
—
|
2.83 µg/mL
Geometric Coefficient of Variation 61
|
6.83 µg/mL
Geometric Coefficient of Variation 16
|
—
|
5.44 µg/mL
Geometric Coefficient of Variation 34
|
—
|
|
Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.08 µg/mL
Geometric Coefficient of Variation 39
|
0.10 µg/mL
Geometric Coefficient of Variation 102
|
—
|
0.13 µg/mL
Geometric Coefficient of Variation 67
|
0.31 µg/mL
Geometric Coefficient of Variation 23
|
—
|
0.27 µg/mL
Geometric Coefficient of Variation 38
|
—
|
|
Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.02 µg/mL
Geometric Coefficient of Variation 101
|
—
|
0.06 µg/mL
Geometric Coefficient of Variation 69
|
0.05 µg/mL
Geometric Coefficient of Variation 87
|
—
|
0.11 µg/mL
Geometric Coefficient of Variation 33
|
0.13 µg/mL
Geometric Coefficient of Variation 31
|
—
|
|
Predicted Concentration at the End of the Dosing Interval (Ctau) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.04 µg/mL
Geometric Coefficient of Variation 102
|
—
|
0.06 µg/mL
Geometric Coefficient of Variation 49
|
0.05 µg/mL
Geometric Coefficient of Variation 96
|
—
|
0.11 µg/mL
Geometric Coefficient of Variation 34
|
0.12 µg/mL
Geometric Coefficient of Variation 34
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized Cmax ((µg/mL)/mg) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.20 (µg/mL)/mg
Geometric Coefficient of Variation 14
|
0.15 (µg/mL)/mg
Geometric Coefficient of Variation 9
|
—
|
0.18 (µg/mL)/mg
Geometric Coefficient of Variation 8
|
0.13 (µg/mL)/mg
Geometric Coefficient of Variation 10
|
—
|
0.13 (µg/mL)/mg
Geometric Coefficient of Variation 14
|
—
|
|
Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 17
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 17
|
—
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 22
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 17
|
—
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 19
|
—
|
|
Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.07 (µg/mL)/mg
Geometric Coefficient of Variation 15
|
—
|
0.06 (µg/mL)/mg
Geometric Coefficient of Variation 22
|
0.07 (µg/mL)/mg
Geometric Coefficient of Variation 16
|
—
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 10
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 11
|
—
|
|
Dose-Normalized Maximum Observed Concentration (Cmax/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.06 (µg/mL)/mg
Geometric Coefficient of Variation 20
|
—
|
0.05 (µg/mL)/mg
Geometric Coefficient of Variation 16
|
0.05 (µg/mL)/mg
Geometric Coefficient of Variation 55
|
—
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 11
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 10
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Median and minimum/maximum of the Tmax (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.50 hours
Interval 0.5 to 0.5
|
1.00 hours
Interval 1.0 to 1.07
|
—
|
1.00 hours
Interval 1.0 to 1.0
|
2.02 hours
Interval 2.0 to 2.03
|
—
|
2.03 hours
Interval 2.02 to 2.03
|
—
|
|
Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.50 hours
Interval 0.5 to 0.5
|
1.00 hours
Interval 1.0 to 1.07
|
—
|
1.00 hours
Interval 1.0 to 1.0
|
2.02 hours
Interval 2.02 to 2.03
|
—
|
2.03 hours
Interval 2.02 to 2.03
|
—
|
|
Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.50 hours
Interval 0.5 to 0.5
|
—
|
1.03 hours
Interval 1.02 to 1.03
|
1.00 hours
Interval 1.0 to 1.0
|
—
|
2.02 hours
Interval 1.03 to 2.02
|
2.03 hours
Interval 2.02 to 2.03
|
—
|
|
Time of Maximum Concentration (Tmax) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.50 hours
Interval 0.5 to 0.5
|
—
|
1.03 hours
Interval 1.02 to 1.03
|
1.00 hours
Interval 1.0 to 2.0
|
—
|
2.02 hours
Interval 1.03 to 2.02
|
2.03 hours
Interval 2.02 to 2.03
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Median and minimum/maximum of the Tmin (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
23.60 hours
Interval 23.6 to 23.7
|
23.65 hours
Interval 23.6 to 23.7
|
—
|
23.60 hours
Interval 23.6 to 23.6
|
23.60 hours
Interval 23.4 to 23.6
|
—
|
23.60 hours
Interval 23.6 to 23.7
|
—
|
|
Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
23.60 hours
Interval 18.0 to 23.7
|
—
|
23.60 hours
Interval 23.6 to 23.7
|
23.60 hours
Interval 18.0 to 23.6
|
—
|
23.60 hours
Interval 23.6 to 23.6
|
23.60 hours
Interval 23.6 to 23.7
|
—
|
|
Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
23.60 hours
Interval 18.0 to 23.6
|
23.60 hours
Interval 18.0 to 23.7
|
—
|
23.60 hours
Interval 23.6 to 23.6
|
23.60 hours
Interval 23.4 to 23.6
|
—
|
23.60 hours
Interval 23.6 to 23.7
|
—
|
|
Time of Minimum Concentration (Tmin) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
18.00 hours
Interval 18.0 to 23.6
|
—
|
23.60 hours
Interval 18.0 to 23.7
|
23.60 hours
Interval 18.0 to 23.6
|
—
|
23.60 hours
Interval 23.6 to 23.6
|
23.60 hours
Interval 23.6 to 23.7
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) extrapolated to the time the concentration is predicted to reach the lower limit of quantification (LLOQ), AUC(0-t) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
723.48 µg*h/mL
Geometric Coefficient of Variation 9
|
1241.47 µg*h/mL
Geometric Coefficient of Variation 18
|
—
|
1377.99 µg*h/mL
Geometric Coefficient of Variation 14
|
2148.23 µg*h/mL
Geometric Coefficient of Variation 11
|
—
|
2024.46 µg*h/mL
Geometric Coefficient of Variation 10
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
39.92 µg*h/mL
Geometric Coefficient of Variation 7
|
83.95 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
102.81 µg*h/mL
Geometric Coefficient of Variation 24
|
187.42 µg*h/mL
Geometric Coefficient of Variation 15
|
—
|
190.43 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
140.00 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
302.40 µg*h/mL
Geometric Coefficient of Variation 18
|
320.50 µg*h/mL
Geometric Coefficient of Variation 20
|
—
|
379.92 µg*h/mL
Geometric Coefficient of Variation 9
|
442.32 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to the Predicted Time the Concentration Reaches the Lower Limit of Quantification (AUC(0-t)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
125.17 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
257.74 µg*h/mL
Geometric Coefficient of Variation 15
|
247.40 µg*h/mL
Geometric Coefficient of Variation 42
|
—
|
379.75 µg*h/mL
Geometric Coefficient of Variation 11
|
427.31 µg*h/mL
Geometric Coefficient of Variation 16
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) to the time of last measured concentration, AUC(0-last) (µg\*h/mL),parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
141.17 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
303.42 µg*h/mL
Geometric Coefficient of Variation 18
|
321.35 µg*h/mL
Geometric Coefficient of Variation 20
|
—
|
381.44 µg*h/mL
Geometric Coefficient of Variation 9
|
443.70 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
126.34 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
259.11 µg*h/mL
Geometric Coefficient of Variation 15
|
248.60 µg*h/mL
Geometric Coefficient of Variation 42
|
—
|
380.91 µg*h/mL
Geometric Coefficient of Variation 11
|
428.67 µg*h/mL
Geometric Coefficient of Variation 16
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
728.18 µg*h/mL
Geometric Coefficient of Variation 9
|
1247.86 µg*h/mL
Geometric Coefficient of Variation 18
|
—
|
1384.69 µg*h/mL
Geometric Coefficient of Variation 14
|
2153.20 µg*h/mL
Geometric Coefficient of Variation 11
|
—
|
2027.57 µg*h/mL
Geometric Coefficient of Variation 10
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to Time of the Last Measured Concentration (AUC(0-last)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
41.04 µg*h/mL
Geometric Coefficient of Variation 7
|
85.03 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
103.94 µg*h/mL
Geometric Coefficient of Variation 23
|
188.66 µg*h/mL
Geometric Coefficient of Variation 15
|
—
|
191.81 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) taken to the limit as the end time becomes arbitrarily large, AUC(0-inf) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
742.95 µg*h/mL
Geometric Coefficient of Variation 10
|
1265.39 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
1404.86 µg*h/mL
Geometric Coefficient of Variation 15
|
2199.93 µg*h/mL
Geometric Coefficient of Variation 11
|
—
|
2065.37 µg*h/mL
Geometric Coefficient of Variation 11
|
—
|
|
Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
141.33 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
303.92 µg*h/mL
Geometric Coefficient of Variation 18
|
322.04 µg*h/mL
Geometric Coefficient of Variation 20
|
—
|
381.76 µg*h/mL
Geometric Coefficient of Variation 9
|
444.34 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
126.50 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
259.27 µg*h/mL
Geometric Coefficient of Variation 15
|
249.11 µg*h/mL
Geometric Coefficient of Variation 41
|
—
|
381.44 µg*h/mL
Geometric Coefficient of Variation 11
|
429.33 µg*h/mL
Geometric Coefficient of Variation 16
|
—
|
|
Area Under the Concentration-Time Curve From Dosing Taken to the Limit as the End Time Becomes Arbitrarily Large (AUC(0-inf)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
41.65 µg*h/mL
Geometric Coefficient of Variation 7
|
85.93 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
104.94 µg*h/mL
Geometric Coefficient of Variation 24
|
190.81 µg*h/mL
Geometric Coefficient of Variation 15
|
—
|
193.61 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) extrapolated to 24 h after dosing, AUC(0-24) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
41.19 µg*h/mL
Geometric Coefficient of Variation 7
|
85.25 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
103.96 µg*h/mL
Geometric Coefficient of Variation 23
|
188.86 µg*h/mL
Geometric Coefficient of Variation 15
|
—
|
192.13 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
126.34 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
259.11 µg*h/mL
Geometric Coefficient of Variation 15
|
248.60 µg*h/mL
Geometric Coefficient of Variation 42
|
—
|
380.91 µg*h/mL
Geometric Coefficient of Variation 11
|
428.67 µg*h/mL
Geometric Coefficient of Variation 16
|
—
|
|
Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
728.97 µg*h/mL
Geometric Coefficient of Variation 9
|
1249.60 µg*h/mL
Geometric Coefficient of Variation 18
|
—
|
1386.28 µg*h/mL
Geometric Coefficient of Variation 14
|
2156.38 µg*h/mL
Geometric Coefficient of Variation 11
|
—
|
2029.12 µg*h/mL
Geometric Coefficient of Variation 10
|
—
|
|
Area Under the Concentration-Time Curve From Dosing Extrapolated to 24 Hours After Dosing (AUC(0-24)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
141.17 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
303.60 µg*h/mL
Geometric Coefficient of Variation 18
|
321.76 µg*h/mL
Geometric Coefficient of Variation 20
|
—
|
381.59 µg*h/mL
Geometric Coefficient of Variation 9
|
443.70 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion), AUC(0-tau) (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
728.97 µg*h/mL
Geometric Coefficient of Variation 9
|
1249.60 µg*h/mL
Geometric Coefficient of Variation 18
|
—
|
1386.28 µg*h/mL
Geometric Coefficient of Variation 14
|
2156.38 µg*h/mL
Geometric Coefficient of Variation 11
|
—
|
2029.12 µg*h/mL
Geometric Coefficient of Variation 10
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
41.19 µg*h/mL
Geometric Coefficient of Variation 7
|
85.25 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
103.96 µg*h/mL
Geometric Coefficient of Variation 23
|
188.86 µg*h/mL
Geometric Coefficient of Variation 15
|
—
|
192.13 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
141.17 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
303.60 µg*h/mL
Geometric Coefficient of Variation 18
|
321.76 µg*h/mL
Geometric Coefficient of Variation 20
|
—
|
381.59 µg*h/mL
Geometric Coefficient of Variation 9
|
443.70 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
126.34 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
259.11 µg*h/mL
Geometric Coefficient of Variation 15
|
248.60 µg*h/mL
Geometric Coefficient of Variation 42
|
—
|
380.91 µg*h/mL
Geometric Coefficient of Variation 11
|
428.67 µg*h/mL
Geometric Coefficient of Variation 16
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion), AUC(0-tau)/Dose ((µg\*h/mL)/mg), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 8
|
—
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 15
|
0.12 (µg*h/mL)/mg
Geometric Coefficient of Variation 41
|
—
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 11
|
0.14 (µg*h/mL)/mg
Geometric Coefficient of Variation 16
|
—
|
|
Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.73 (µg*h/mL)/mg
Geometric Coefficient of Variation 9
|
0.62 (µg*h/mL)/mg
Geometric Coefficient of Variation 18
|
—
|
0.69 (µg*h/mL)/mg
Geometric Coefficient of Variation 15
|
0.72 (µg*h/mL)/mg
Geometric Coefficient of Variation 11
|
—
|
0.68 (µg*h/mL)/mg
Geometric Coefficient of Variation 10
|
—
|
|
Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.04 (µg*h/mL)/mg
Geometric Coefficient of Variation 7
|
0.04 (µg*h/mL)/mg
Geometric Coefficient of Variation 19
|
—
|
0.05 (µg*h/mL)/mg
Geometric Coefficient of Variation 24
|
0.06 (µg*h/mL)/mg
Geometric Coefficient of Variation 15
|
—
|
0.06 (µg*h/mL)/mg
Geometric Coefficient of Variation 14
|
—
|
|
Dose-Normalized Area Under the Concentration-Time Curve From Dosing to the End of the Dosing Interval (AUC(0-tau)/Dose) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.14 (µg*h/mL)/mg
Geometric Coefficient of Variation 8
|
—
|
0.15 (µg*h/mL)/mg
Geometric Coefficient of Variation 18
|
0.16 (µg*h/mL)/mg
Geometric Coefficient of Variation 20
|
—
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 9
|
0.15 (µg*h/mL)/mg
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the terminal elimination half-life, t1/2 (h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
4.09 hours
Geometric Coefficient of Variation 11
|
3.83 hours
Geometric Coefficient of Variation 21
|
—
|
3.86 hours
Geometric Coefficient of Variation 15
|
3.96 hours
Geometric Coefficient of Variation 12
|
—
|
3.87 hours
Geometric Coefficient of Variation 10
|
—
|
|
Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
4.34 hours
Geometric Coefficient of Variation 12
|
3.76 hours
Geometric Coefficient of Variation 22
|
—
|
3.92 hours
Geometric Coefficient of Variation 14
|
4.20 hours
Geometric Coefficient of Variation 4
|
—
|
4.20 hours
Geometric Coefficient of Variation 10
|
—
|
|
Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
2.35 hours
Geometric Coefficient of Variation 15
|
—
|
2.60 hours
Geometric Coefficient of Variation 14
|
2.57 hours
Geometric Coefficient of Variation 12
|
—
|
2.61 hours
Geometric Coefficient of Variation 9
|
2.71 hours
Geometric Coefficient of Variation 6
|
—
|
|
Terminal Elimination Half-Life (t1/2) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
2.75 hours
Geometric Coefficient of Variation 18
|
—
|
2.81 hours
Geometric Coefficient of Variation 14
|
2.63 hours
Geometric Coefficient of Variation 15
|
—
|
2.69 hours
Geometric Coefficient of Variation 9
|
2.71 hours
Geometric Coefficient of Variation 5
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total clearance, CLT (L/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
1.34 L/h
Geometric Coefficient of Variation 10
|
1.58 L/h
Geometric Coefficient of Variation 19
|
—
|
1.42 L/h
Geometric Coefficient of Variation 15
|
1.37 L/h
Geometric Coefficient of Variation 11
|
—
|
1.45 L/h
Geometric Coefficient of Variation 11
|
—
|
|
Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
7.07 L/h
Geometric Coefficient of Variation 8
|
—
|
6.58 L/h
Geometric Coefficient of Variation 18
|
6.21 L/h
Geometric Coefficient of Variation 20
|
—
|
7.86 L/h
Geometric Coefficient of Variation 9
|
6.75 L/h
Geometric Coefficient of Variation 14
|
—
|
|
Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
23.99 L/h
Geometric Coefficient of Variation 7
|
23.28 L/h
Geometric Coefficient of Variation 19
|
—
|
19.06 L/h
Geometric Coefficient of Variation 24
|
15.70 L/h
Geometric Coefficient of Variation 15
|
—
|
15.50 L/h
Geometric Coefficient of Variation 14
|
—
|
|
Total Clearance (CLT) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
7.91 L/h
Geometric Coefficient of Variation 8
|
—
|
7.71 L/h
Geometric Coefficient of Variation 15
|
8.03 L/h
Geometric Coefficient of Variation 41
|
—
|
7.86 L/h
Geometric Coefficient of Variation 11
|
6.99 L/h
Geometric Coefficient of Variation 16
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the first-order terminal phase elimination rate constant, Ke (1/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.17 1/h
Geometric Coefficient of Variation 11
|
0.18 1/h
Geometric Coefficient of Variation 21
|
—
|
0.18 1/h
Geometric Coefficient of Variation 15
|
0.18 1/h
Geometric Coefficient of Variation 12
|
—
|
0.18 1/h
Geometric Coefficient of Variation 10
|
—
|
|
First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.16 1/h
Geometric Coefficient of Variation 12
|
0.18 1/h
Geometric Coefficient of Variation 22
|
—
|
0.18 1/h
Geometric Coefficient of Variation 14
|
0.17 1/h
Geometric Coefficient of Variation 4
|
—
|
0.17 1/h
Geometric Coefficient of Variation 10
|
—
|
|
First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.30 1/h
Geometric Coefficient of Variation 15
|
—
|
0.27 1/h
Geometric Coefficient of Variation 14
|
0.27 1/h
Geometric Coefficient of Variation 12
|
—
|
0.27 1/h
Geometric Coefficient of Variation 9
|
0.26 1/h
Geometric Coefficient of Variation 6
|
—
|
|
First-Order Terminal Phase Elimination Rate Constant (Ke) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.25 1/h
Geometric Coefficient of Variation 18
|
—
|
0.25 1/h
Geometric Coefficient of Variation 14
|
0.26 1/h
Geometric Coefficient of Variation 14
|
—
|
0.26 1/h
Geometric Coefficient of Variation 9
|
0.26 1/h
Geometric Coefficient of Variation 5
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the apparent volume of distribution, Vd (L), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 1 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
8.43 liters
Geometric Coefficient of Variation 7
|
8.57 liters
Geometric Coefficient of Variation 9
|
—
|
8.04 liters
Geometric Coefficient of Variation 12
|
8.28 liters
Geometric Coefficient of Variation 10
|
—
|
8.81 liters
Geometric Coefficient of Variation 13
|
—
|
|
Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
23.97 liters
Geometric Coefficient of Variation 14
|
—
|
24.67 liters
Geometric Coefficient of Variation 28
|
23.05 liters
Geometric Coefficient of Variation 22
|
—
|
29.56 liters
Geometric Coefficient of Variation 10
|
26.43 liters
Geometric Coefficient of Variation 16
|
—
|
|
Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
141.43 liters
Geometric Coefficient of Variation 11
|
128.25 liters
Geometric Coefficient of Variation 12
|
—
|
106.20 liters
Geometric Coefficient of Variation 23
|
89.98 liters
Geometric Coefficient of Variation 20
|
—
|
86.55 liters
Geometric Coefficient of Variation 16
|
—
|
|
Apparent Volume of Distribution (Vd) for Dose 1 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
31.37 liters
Geometric Coefficient of Variation 12
|
—
|
31.18 liters
Geometric Coefficient of Variation 23
|
30.42 liters
Geometric Coefficient of Variation 40
|
—
|
30.52 liters
Geometric Coefficient of Variation 9
|
27.28 liters
Geometric Coefficient of Variation 17
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmax,ss (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. These estimates assume steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
181.90 µg/mL
Geometric Coefficient of Variation 11
|
341.92 µg/mL
Geometric Coefficient of Variation 10
|
—
|
344.89 µg/mL
Geometric Coefficient of Variation 10
|
387.57 µg/mL
Geometric Coefficient of Variation 9
|
—
|
343.24 µg/mL
Geometric Coefficient of Variation 13
|
—
|
|
Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
15.41 µg/mL
Geometric Coefficient of Variation 24
|
38.18 µg/mL
Geometric Coefficient of Variation 13
|
—
|
36.09 µg/mL
Geometric Coefficient of Variation 23
|
57.65 µg/mL
Geometric Coefficient of Variation 28
|
—
|
50.36 µg/mL
Geometric Coefficient of Variation 28
|
—
|
|
Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
63.87 µg/mL
Geometric Coefficient of Variation 17
|
—
|
115.71 µg/mL
Geometric Coefficient of Variation 16
|
130.69 µg/mL
Geometric Coefficient of Variation 18
|
—
|
109.41 µg/mL
Geometric Coefficient of Variation 7
|
113.79 µg/mL
Geometric Coefficient of Variation 16
|
—
|
|
Maximum Observed Concentration at Steady State (Cmax,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
57.89 µg/mL
Geometric Coefficient of Variation 23
|
—
|
103.12 µg/mL
Geometric Coefficient of Variation 18
|
83.36 µg/mL
Geometric Coefficient of Variation 57
|
—
|
111.59 µg/mL
Geometric Coefficient of Variation 7
|
111.81 µg/mL
Geometric Coefficient of Variation 16
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the Cmin,ss (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. These estimates assume steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.13 µg/mL
Geometric Coefficient of Variation 49
|
—
|
0.12 µg/mL
Geometric Coefficient of Variation 68
|
0.10 µg/mL
Geometric Coefficient of Variation 46
|
—
|
0.13 µg/mL
Geometric Coefficient of Variation 27
|
0.12 µg/mL
Geometric Coefficient of Variation 36
|
—
|
|
Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.12 µg/mL
Geometric Coefficient of Variation 66
|
—
|
0.10 µg/mL
Geometric Coefficient of Variation 38
|
0.17 µg/mL
Geometric Coefficient of Variation 864
|
—
|
0.14 µg/mL
Geometric Coefficient of Variation 23
|
0.11 µg/mL
Geometric Coefficient of Variation 34
|
—
|
|
Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
1.75 µg/mL
Geometric Coefficient of Variation 30
|
1.81 µg/mL
Geometric Coefficient of Variation 114
|
—
|
1.74 µg/mL
Geometric Coefficient of Variation 75
|
4.93 µg/mL
Geometric Coefficient of Variation 2
|
—
|
3.49 µg/mL
Geometric Coefficient of Variation 65
|
—
|
|
Minimum Observed Concentration at Steady State (Cmin,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.10 µg/mL
Geometric Coefficient of Variation 28
|
0.12 µg/mL
Geometric Coefficient of Variation 35
|
—
|
0.12 µg/mL
Geometric Coefficient of Variation 60
|
0.23 µg/mL
Geometric Coefficient of Variation 31
|
—
|
0.15 µg/mL
Geometric Coefficient of Variation 59
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized Cmax,ss ((µg/mL)/mg) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. This estimate assumes steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 24
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 13
|
—
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 23
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 28
|
—
|
0.02 (µg/mL)/mg
Geometric Coefficient of Variation 28
|
—
|
|
Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.06 (µg/mL)/mg
Geometric Coefficient of Variation 17
|
—
|
0.06 (µg/mL)/mg
Geometric Coefficient of Variation 16
|
0.07 (µg/mL)/mg
Geometric Coefficient of Variation 18
|
—
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 7
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 16
|
—
|
|
Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.06 (µg/mL)/mg
Geometric Coefficient of Variation 23
|
—
|
0.05 (µg/mL)/mg
Geometric Coefficient of Variation 18
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 56
|
—
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 7
|
0.04 (µg/mL)/mg
Geometric Coefficient of Variation 15
|
—
|
|
Dose-Normalized Maximum Observed Concentration at Steady State (Cmax,ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.18 (µg/mL)/mg
Geometric Coefficient of Variation 11
|
0.17 (µg/mL)/mg
Geometric Coefficient of Variation 10
|
—
|
0.17 (µg/mL)/mg
Geometric Coefficient of Variation 10
|
0.13 (µg/mL)/mg
Geometric Coefficient of Variation 9
|
—
|
0.11 (µg/mL)/mg
Geometric Coefficient of Variation 13
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the average concentration over the Dose 7 dosing interval, Cavg (µg/mL) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). Cavg is calculated as AUC(0-tau,ss)/tau. These estimates assume steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
29.99 µg/mL
Geometric Coefficient of Variation 9
|
51.20 µg/mL
Geometric Coefficient of Variation 13
|
—
|
51.40 µg/mL
Geometric Coefficient of Variation 16
|
80.91 µg/mL
Geometric Coefficient of Variation 6
|
—
|
71.98 µg/mL
Geometric Coefficient of Variation 14
|
—
|
|
Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
1.64 µg/mL
Geometric Coefficient of Variation 6
|
3.51 µg/mL
Geometric Coefficient of Variation 18
|
—
|
3.77 µg/mL
Geometric Coefficient of Variation 16
|
7.01 µg/mL
Geometric Coefficient of Variation 23
|
—
|
6.29 µg/mL
Geometric Coefficient of Variation 19
|
—
|
|
Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
5.56 µg/mL
Geometric Coefficient of Variation 8
|
—
|
11.94 µg/mL
Geometric Coefficient of Variation 20
|
12.83 µg/mL
Geometric Coefficient of Variation 19
|
—
|
16.05 µg/mL
Geometric Coefficient of Variation 7
|
16.52 µg/mL
Geometric Coefficient of Variation 14
|
—
|
|
Average Concentration Over the Dose 7 Dosing Interval (Cavg) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
5.03 µg/mL
Geometric Coefficient of Variation 8
|
—
|
10.48 µg/mL
Geometric Coefficient of Variation 20
|
9.77 µg/mL
Geometric Coefficient of Variation 30
|
—
|
16.32 µg/mL
Geometric Coefficient of Variation 8
|
15.83 µg/mL
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the predicted concentration at the end of the dosing interval at steady state, Ctau,ss (µg/mL), parameters estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). These estimates assume steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
1.75 µg/mL
Geometric Coefficient of Variation 30
|
1.85 µg/mL
Geometric Coefficient of Variation 111
|
—
|
1.74 µg/mL
Geometric Coefficient of Variation 75
|
4.93 µg/mL
Geometric Coefficient of Variation 2
|
—
|
3.50 µg/mL
Geometric Coefficient of Variation 64
|
—
|
|
Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.06 µg/mL
Geometric Coefficient of Variation 53
|
0.07 µg/mL
Geometric Coefficient of Variation 128
|
—
|
0.07 µg/mL
Geometric Coefficient of Variation 88
|
0.23 µg/mL
Geometric Coefficient of Variation 31
|
—
|
0.15 µg/mL
Geometric Coefficient of Variation 58
|
—
|
|
Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.02 µg/mL
Geometric Coefficient of Variation 68
|
—
|
0.06 µg/mL
Geometric Coefficient of Variation 89
|
0.05 µg/mL
Geometric Coefficient of Variation 176
|
—
|
0.13 µg/mL
Geometric Coefficient of Variation 28
|
0.12 µg/mL
Geometric Coefficient of Variation 35
|
—
|
|
Predicted Concentration at the End of the Dosing Interval at Steady State (Ctau,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.06 µg/mL
Geometric Coefficient of Variation 169
|
—
|
0.07 µg/mL
Geometric Coefficient of Variation 90
|
0.11 µg/mL
Geometric Coefficient of Variation 2318
|
—
|
0.14 µg/mL
Geometric Coefficient of Variation 23
|
0.11 µg/mL
Geometric Coefficient of Variation 34
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Median and minimum/maximum of the Tmax,ss (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group. The estimate for Tmax,ss assumes steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.52 hours
Interval 0.5 to 0.6
|
1.00 hours
Interval 1.0 to 1.0
|
—
|
1.02 hours
Interval 1.0 to 1.02
|
2.02 hours
Interval 2.02 to 2.02
|
—
|
2.07 hours
Interval 2.02 to 2.23
|
—
|
|
Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.52 hours
Interval 0.25 to 0.6
|
1.00 hours
Interval 1.0 to 1.0
|
—
|
1.02 hours
Interval 0.5 to 1.02
|
2.02 hours
Interval 2.02 to 2.02
|
—
|
2.07 hours
Interval 2.02 to 2.23
|
—
|
|
Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.52 hours
Interval 0.25 to 0.6
|
—
|
1.00 hours
Interval 1.0 to 1.0
|
1.02 hours
Interval 1.0 to 1.02
|
—
|
2.02 hours
Interval 2.02 to 2.07
|
2.07 hours
Interval 2.02 to 2.23
|
—
|
|
Time of Maximum Concentration at Steady State (Tmax,ss) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.52 hours
Interval 0.25 to 0.6
|
—
|
1.00 hours
Interval 1.0 to 1.0
|
1.02 hours
Interval 1.0 to 2.0
|
—
|
2.02 hours
Interval 2.02 to 2.07
|
2.07 hours
Interval 2.02 to 2.23
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Median and minimum/maximum of the Tmin (h) parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
24.00 hours
Interval 18.0 to 24.0
|
—
|
24.00 hours
Interval 18.1 to 24.0
|
24.00 hours
Interval 18.0 to 24.0
|
—
|
24.00 hours
Interval 24.0 to 24.1
|
24.00 hours
Interval 24.0 to 24.1
|
—
|
|
Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
24.00 hours
Interval 24.0 to 24.0
|
24.05 hours
Interval 24.0 to 24.3
|
—
|
24.00 hours
Interval 24.0 to 24.0
|
24.00 hours
Interval 24.0 to 24.0
|
—
|
24.00 hours
Interval 24.0 to 24.1
|
—
|
|
Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
24.00 hours
Interval 18.0 to 24.0
|
24.00 hours
Interval 18.0 to 24.1
|
—
|
24.00 hours
Interval 18.0 to 24.0
|
24.00 hours
Interval 24.0 to 24.0
|
—
|
24.00 hours
Interval 24.0 to 24.1
|
—
|
|
Time of Minimum Concentration (Tmin) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
18.00 hours
Interval 18.0 to 24.0
|
—
|
24.00 hours
Interval 18.0 to 24.0
|
24.00 hours
Interval 18.0 to 24.0
|
—
|
24.00 hours
Interval 24.0 to 24.1
|
24.00 hours
Interval 24.0 to 24.1
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the area under the concentration-time curve from dosing (time 0 h) extrapolated to 24 h after dosing at steady state, AUC(0-24),ss (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
719.86 µg*h/mL
Geometric Coefficient of Variation 9
|
1228.88 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
1233.66 µg*h/mL
Geometric Coefficient of Variation 16
|
1940.84 µg*h/mL
Geometric Coefficient of Variation 6
|
—
|
1726.43 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
133.35 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
286.34 µg*h/mL
Geometric Coefficient of Variation 20
|
308.35 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
384.53 µg*h/mL
Geometric Coefficient of Variation 7
|
396.60 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
39.48 µg*h/mL
Geometric Coefficient of Variation 6
|
84.22 µg*h/mL
Geometric Coefficient of Variation 18
|
—
|
90.51 µg*h/mL
Geometric Coefficient of Variation 16
|
168.05 µg*h/mL
Geometric Coefficient of Variation 23
|
—
|
150.93 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
|
Area Under the Concentration-Time Curve From Dose 7 Dosing Extrapolated to 24 Hours After Dosing at Steady State (AUC(0-24),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
120.70 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
251.56 µg*h/mL
Geometric Coefficient of Variation 20
|
234.14 µg*h/mL
Geometric Coefficient of Variation 30
|
—
|
392.09 µg*h/mL
Geometric Coefficient of Variation 8
|
380.11 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion) at steady state, AUC(0-tau),ss (µg\*h/mL), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
719.86 µg*h/mL
Geometric Coefficient of Variation 9
|
1228.88 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
1233.66 µg*h/mL
Geometric Coefficient of Variation 16
|
1940.84 µg*h/mL
Geometric Coefficient of Variation 6
|
—
|
1726.43 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
39.48 µg*h/mL
Geometric Coefficient of Variation 6
|
84.22 µg*h/mL
Geometric Coefficient of Variation 18
|
—
|
90.51 µg*h/mL
Geometric Coefficient of Variation 16
|
168.05 µg*h/mL
Geometric Coefficient of Variation 23
|
—
|
150.93 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
|
Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
133.35 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
286.34 µg*h/mL
Geometric Coefficient of Variation 20
|
308.35 µg*h/mL
Geometric Coefficient of Variation 19
|
—
|
384.53 µg*h/mL
Geometric Coefficient of Variation 7
|
396.60 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
|
Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
120.70 µg*h/mL
Geometric Coefficient of Variation 8
|
—
|
251.56 µg*h/mL
Geometric Coefficient of Variation 20
|
234.14 µg*h/mL
Geometric Coefficient of Variation 30
|
—
|
392.09 µg*h/mL
Geometric Coefficient of Variation 8
|
380.11 µg*h/mL
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the dose-normalized total area under the concentration-time curve from dosing (time 0 h) to the end of the dosing interval (24 h post-infusion) at steady state, AUC(0-tau),ss/Dose ((µg\*h/mL)/mg), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.72 (µg*h/mL)/mg
Geometric Coefficient of Variation 9
|
0.61 (µg*h/mL)/mg
Geometric Coefficient of Variation 13
|
—
|
0.62 (µg*h/mL)/mg
Geometric Coefficient of Variation 16
|
0.65 (µg*h/mL)/mg
Geometric Coefficient of Variation 6
|
—
|
0.58 (µg*h/mL)/mg
Geometric Coefficient of Variation 14
|
—
|
|
Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.04 (µg*h/mL)/mg
Geometric Coefficient of Variation 6
|
0.04 (µg*h/mL)/mg
Geometric Coefficient of Variation 18
|
—
|
0.05 (µg*h/mL)/mg
Geometric Coefficient of Variation 16
|
0.06 (µg*h/mL)/mg
Geometric Coefficient of Variation 23
|
—
|
0.05 (µg*h/mL)/mg
Geometric Coefficient of Variation 19
|
—
|
|
Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 8
|
—
|
0.14 (µg*h/mL)/mg
Geometric Coefficient of Variation 20
|
0.15 (µg*h/mL)/mg
Geometric Coefficient of Variation 19
|
—
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 7
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 14
|
—
|
|
Dose-Normalized Area Under the Concentration-Time Curve From Dose 7 Dosing to the End of the Dosing Interval at Steady State (AUC(0-tau),ss/Dose) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.12 (µg*h/mL)/mg
Geometric Coefficient of Variation 8
|
—
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 20
|
0.12 (µg*h/mL)/mg
Geometric Coefficient of Variation 30
|
—
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 8
|
0.13 (µg*h/mL)/mg
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the terminal elimination half-life, t1/2 (h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
3.89 hours
Geometric Coefficient of Variation 19
|
3.45 hours
Geometric Coefficient of Variation 19
|
—
|
3.38 hours
Geometric Coefficient of Variation 19
|
3.77 hours
Geometric Coefficient of Variation 10
|
—
|
3.76 hours
Geometric Coefficient of Variation 17
|
—
|
|
Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
3.91 hours
Geometric Coefficient of Variation 8
|
3.64 hours
Geometric Coefficient of Variation 19
|
—
|
3.67 hours
Geometric Coefficient of Variation 21
|
4.14 hours
Geometric Coefficient of Variation 4
|
—
|
3.86 hours
Geometric Coefficient of Variation 18
|
—
|
|
Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
2.32 hours
Geometric Coefficient of Variation 15
|
—
|
2.64 hours
Geometric Coefficient of Variation 12
|
2.47 hours
Geometric Coefficient of Variation 24
|
—
|
2.69 hours
Geometric Coefficient of Variation 3
|
2.65 hours
Geometric Coefficient of Variation 10
|
—
|
|
Terminal Elimination Half-Life (t1/2) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
2.55 hours
Geometric Coefficient of Variation 11
|
—
|
2.78 hours
Geometric Coefficient of Variation 15
|
3.13 hours
Geometric Coefficient of Variation 55
|
—
|
2.65 hours
Geometric Coefficient of Variation 7
|
2.70 hours
Geometric Coefficient of Variation 8
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the total clearance, CLT (L/h), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration).
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
1.39 L/h
Geometric Coefficient of Variation 9
|
1.63 L/h
Geometric Coefficient of Variation 13
|
—
|
1.62 L/h
Geometric Coefficient of Variation 16
|
1.55 L/h
Geometric Coefficient of Variation 7
|
—
|
1.74 L/h
Geometric Coefficient of Variation 14
|
—
|
|
Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
25.35 L/h
Geometric Coefficient of Variation 6
|
23.75 L/h
Geometric Coefficient of Variation 18
|
—
|
22.09 L/h
Geometric Coefficient of Variation 16
|
17.83 L/h
Geometric Coefficient of Variation 23
|
—
|
19.86 L/h
Geometric Coefficient of Variation 19
|
—
|
|
Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
7.50 L/h
Geometric Coefficient of Variation 8
|
—
|
6.98 L/h
Geometric Coefficient of Variation 20
|
6.49 L/h
Geometric Coefficient of Variation 19
|
—
|
7.80 L/h
Geometric Coefficient of Variation 7
|
7.56 L/h
Geometric Coefficient of Variation 14
|
—
|
|
Total Clearance (CLT) for Dose 7 of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
8.28 L/h
Geometric Coefficient of Variation 8
|
—
|
7.96 L/h
Geometric Coefficient of Variation 20
|
8.54 L/h
Geometric Coefficient of Variation 30
|
—
|
7.65 L/h
Geometric Coefficient of Variation 8
|
7.89 L/h
Geometric Coefficient of Variation 14
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of Dose 7 (Day 7) dosing and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the apparent volume of distribution at steady state, Vd,ss (L), parameter estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h period following Dose 7 by dose group using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). This estimate assumes steady state has been achieved.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
18.04 liters
Geometric Coefficient of Variation 14
|
—
|
16.57 liters
Geometric Coefficient of Variation 18
|
13.88 liters
Geometric Coefficient of Variation 21
|
—
|
20.33 liters
Geometric Coefficient of Variation 7
|
19.35 liters
Geometric Coefficient of Variation 13
|
—
|
|
Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
6.86 liters
Geometric Coefficient of Variation 5
|
6.73 liters
Geometric Coefficient of Variation 11
|
—
|
6.51 liters
Geometric Coefficient of Variation 11
|
7.17 liters
Geometric Coefficient of Variation 9
|
—
|
7.58 liters
Geometric Coefficient of Variation 10
|
—
|
|
Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
105.98 liters
Geometric Coefficient of Variation 14
|
72.51 liters
Geometric Coefficient of Variation 16
|
—
|
69.65 liters
Geometric Coefficient of Variation 13
|
56.84 liters
Geometric Coefficient of Variation 30
|
—
|
61.59 liters
Geometric Coefficient of Variation 29
|
—
|
|
Apparent Volume of Distribution at Steady State (Vd,ss) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
21.86 liters
Geometric Coefficient of Variation 10
|
—
|
18.79 liters
Geometric Coefficient of Variation 14
|
30.21 liters
Geometric Coefficient of Variation 197
|
—
|
20.17 liters
Geometric Coefficient of Variation 6
|
19.69 liters
Geometric Coefficient of Variation 13
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusionsPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the linearity index (ratio) for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. The linearity index is a measure of how linear the relationship is between increase in administered dose and increase in exposure. The linearity index is estimated as AUC(0-tau),ss (Dose 7)/AUC(0-inf) (Dose 1), where the areas under the concentration-time curves from Dose 7 to the end of the dosing interval at steady state and from Dose 1 taken to the limit as the end time becomes arbitrarily large, AUC(0-tau),ss and AUC(0-inf) respectively, are calculated using Phoenix WinNonlin Non-compartmental Analysis with Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). The AUC(0-tau),ss estimate assumes steady state was reached.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.97 ratio
Geometric Coefficient of Variation 4
|
0.97 ratio
Geometric Coefficient of Variation 7
|
—
|
0.88 ratio
Geometric Coefficient of Variation 11
|
0.89 ratio
Geometric Coefficient of Variation 6
|
—
|
0.84 ratio
Geometric Coefficient of Variation 9
|
—
|
|
Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.95 ratio
Geometric Coefficient of Variation 4
|
0.98 ratio
Geometric Coefficient of Variation 4
|
—
|
0.86 ratio
Geometric Coefficient of Variation 18
|
0.88 ratio
Geometric Coefficient of Variation 9
|
—
|
0.78 ratio
Geometric Coefficient of Variation 17
|
—
|
|
Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.94 ratio
Geometric Coefficient of Variation 4
|
—
|
0.94 ratio
Geometric Coefficient of Variation 13
|
0.96 ratio
Geometric Coefficient of Variation 5
|
—
|
1.01 ratio
Geometric Coefficient of Variation 8
|
0.89 ratio
Geometric Coefficient of Variation 11
|
—
|
|
Linearity Index of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.95 ratio
Geometric Coefficient of Variation 5
|
—
|
0.97 ratio
Geometric Coefficient of Variation 13
|
0.94 ratio
Geometric Coefficient of Variation 26
|
—
|
1.03 ratio
Geometric Coefficient of Variation 7
|
0.89 ratio
Geometric Coefficient of Variation 13
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusionsPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the accumulation ratio of the AUC, RAUC (ratio), parameter for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. RAUC is estimated as AUC(0-tau),ss (Dose 7)/AUC(0-24) (Dose 1), where the areas under the concentration-time curves from Dose 7 to the end of the dosing interval at steady state and from Dose 1 extrapolated to 24 h after Dose 1, AUC(0-tau),ss and AUC(0-24) respectively, are calculated using Phoenix WinNonlin Non-compartmental Analysis with the Ke (first-order terminal phase elimination rate constant) acceptance criteria: Rsq\_adjusted (adjusted R-squared) = 0.90 and includes at least 3 timepoints after Tmax (time of maximum concentration). The AUC(0-tau),ss estimate assumes steady state was reached.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.99 ratio
Geometric Coefficient of Variation 5
|
0.98 ratio
Geometric Coefficient of Variation 7
|
—
|
0.89 ratio
Geometric Coefficient of Variation 11
|
0.91 ratio
Geometric Coefficient of Variation 6
|
—
|
0.85 ratio
Geometric Coefficient of Variation 9
|
—
|
|
The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.96 ratio
Geometric Coefficient of Variation 4
|
0.99 ratio
Geometric Coefficient of Variation 3
|
—
|
0.87 ratio
Geometric Coefficient of Variation 18
|
0.89 ratio
Geometric Coefficient of Variation 9
|
—
|
0.79 ratio
Geometric Coefficient of Variation 17
|
—
|
|
The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.94 ratio
Geometric Coefficient of Variation 4
|
—
|
0.94 ratio
Geometric Coefficient of Variation 13
|
0.96 ratio
Geometric Coefficient of Variation 5
|
—
|
1.01 ratio
Geometric Coefficient of Variation 8
|
0.89 ratio
Geometric Coefficient of Variation 11
|
—
|
|
The Accumulation Ratio of the Area Under the Concentration-Time Curve (RAUC) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.96 ratio
Geometric Coefficient of Variation 5
|
—
|
0.97 ratio
Geometric Coefficient of Variation 13
|
0.94 ratio
Geometric Coefficient of Variation 26
|
—
|
1.03 ratio
Geometric Coefficient of Variation 7
|
0.89 ratio
Geometric Coefficient of Variation 13
|
—
|
SECONDARY outcome
Timeframe: =0.5 h prior to the start of and 0.25 h (WCK 6777 2g group only), 0.5 h (WCK 6777 2g, ERT 2g, ZID 2g, and WCK 6777 4g groups only), 1 h, 2 h, 3 h, 4 h, 8 h, 12 h, 18 h, and 24 h post-start of Dose 1 (Day 1) and Dose 7 (Day 7) infusionsPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of the accumulation ratio of the Cmax, RCmax (ratio), parameter for the total ERT, free ERT, total ZID, and free ZID plasma concentration-time data by dose group. RCmax is estimated as Cmax (Dose 7)/Cmax (Dose 1), where the Cmax parameters are estimated from the total ERT, free ERT, total ZID, or free ZID plasma concentration-time data over the 24-h periods following Dose 1 and Dose 7, respectively.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ZID
|
0.92 ratio
Geometric Coefficient of Variation 15
|
—
|
0.96 ratio
Geometric Coefficient of Variation 11
|
0.98 ratio
Geometric Coefficient of Variation 12
|
—
|
0.98 ratio
Geometric Coefficient of Variation 13
|
0.89 ratio
Geometric Coefficient of Variation 17
|
—
|
|
The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ZID
|
0.90 ratio
Geometric Coefficient of Variation 15
|
—
|
0.98 ratio
Geometric Coefficient of Variation 11
|
0.85 ratio
Geometric Coefficient of Variation 40
|
—
|
1.03 ratio
Geometric Coefficient of Variation 10
|
0.89 ratio
Geometric Coefficient of Variation 13
|
—
|
|
The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Total ERT
|
0.92 ratio
Geometric Coefficient of Variation 17
|
1.13 ratio
Geometric Coefficient of Variation 14
|
—
|
0.97 ratio
Geometric Coefficient of Variation 7
|
1.01 ratio
Geometric Coefficient of Variation 8
|
—
|
0.88 ratio
Geometric Coefficient of Variation 8
|
—
|
|
The Accumulation Ratio of the Maximum Observed Concentration (RCmax) of Total ERT, Free ERT, Total ZID, and Free ZID in Plasma
Free ERT
|
0.93 ratio
Geometric Coefficient of Variation 11
|
1.12 ratio
Geometric Coefficient of Variation 7
|
—
|
0.86 ratio
Geometric Coefficient of Variation 37
|
0.99 ratio
Geometric Coefficient of Variation 12
|
—
|
0.85 ratio
Geometric Coefficient of Variation 28
|
—
|
SECONDARY outcome
Timeframe: 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Mean and minimum/maximum of the amount of unchanged ERT and the amount of unchanged ZID excreted in urine, Ae,urine (mg), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 1 by dose group. Ae,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ERT - 8-12 h
|
64.30 mg
Interval 19.8 to 83.8
|
122.38 mg
Interval 58.8 to 204.0
|
—
|
128.93 mg
Interval 77.5 to 202.0
|
173.50 mg
Interval 128.0 to 227.0
|
—
|
192.00 mg
Interval 112.0 to 305.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ZID - 8-12 h
|
33.28 mg
Interval 6.88 to 51.3
|
—
|
80.35 mg
Interval 56.9 to 162.0
|
83.72 mg
Interval 38.2 to 123.0
|
—
|
143.50 mg
Interval 104.0 to 254.0
|
167.67 mg
Interval 127.0 to 216.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ZID - 12-24 h
|
19.93 mg
Interval 13.3 to 24.3
|
—
|
27.02 mg
Interval 15.1 to 54.1
|
25.53 mg
Interval 18.0 to 37.0
|
—
|
75.35 mg
Interval 37.6 to 110.0
|
75.83 mg
Interval 21.5 to 176.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ERT - 0-4 h
|
339.62 mg
Interval 97.7 to 605.0
|
748.60 mg
Interval 573.0 to 995.0
|
—
|
794.50 mg
Interval 414.0 to 1620.0
|
768.60 mg
Interval 451.0 to 1090.0
|
—
|
670.13 mg
Interval 87.8 to 1630.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ERT - 4-8 h
|
159.23 mg
Interval 74.2 to 268.0
|
275.67 mg
Interval 105.0 to 414.0
|
—
|
202.67 mg
Interval 163.0 to 272.0
|
713.50 mg
Interval 393.0 to 1850.0
|
—
|
605.83 mg
Interval 246.0 to 1390.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ERT - 12-24 h
|
49.80 mg
Interval 25.6 to 66.5
|
84.22 mg
Interval 49.9 to 150.0
|
—
|
54.38 mg
Interval 19.2 to 106.0
|
149.15 mg
Interval 84.5 to 235.0
|
—
|
106.95 mg
Interval 58.5 to 158.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ZID - 0-4 h
|
544.83 mg
Interval 259.0 to 816.0
|
—
|
1336.67 mg
Interval 1060.0 to 1620.0
|
1475.00 mg
Interval 1080.0 to 2040.0
|
—
|
1838.33 mg
Interval 1270.0 to 2110.0
|
1366.50 mg
Interval 248.0 to 2080.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ZID - 4-8 h
|
150.55 mg
Interval 62.6 to 277.0
|
—
|
360.00 mg
Interval 250.0 to 552.0
|
259.00 mg
Interval 149.0 to 314.0
|
—
|
631.67 mg
Interval 324.0 to 810.0
|
1006.00 mg
Interval 528.0 to 2600.0
|
—
|
SECONDARY outcome
Timeframe: 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Mean and minimum/maximum of the cumulative amount of unchanged ERT and the cumulative amount of unchanged ZID excreted in urine from zero (predose) to 24 h following Dose 1, Ae,urine(0-24) (mg), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24))
Unchanged ERT
|
594.00 mg
Interval 204.0 to 856.0
|
1085.67 mg
Interval 321.0 to 1490.0
|
—
|
1181.83 mg
Interval 711.0 to 2190.0
|
1676.67 mg
Interval 1200.0 to 2160.0
|
—
|
1572.17 mg
Interval 843.0 to 2400.0
|
—
|
|
Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 1 (Ae,Urine(0-24))
Unchanged ZID
|
733.17 mg
Interval 370.0 to 922.0
|
—
|
1798.33 mg
Interval 1470.0 to 1960.0
|
1836.67 mg
Interval 1420.0 to 2420.0
|
—
|
2688.33 mg
Interval 1820.0 to 3090.0
|
2620.00 mg
Interval 1040.0 to 3180.0
|
—
|
SECONDARY outcome
Timeframe: 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 (Day 1) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine, fe,urine (%), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 1 by dose group. These fe,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ERT- 0-4 h
|
33.96 % of dose excreted unchanged
Interval 9.77 to 60.5
|
37.46 % of dose excreted unchanged
Interval 28.7 to 49.8
|
—
|
39.75 % of dose excreted unchanged
Interval 20.7 to 81.2
|
25.60 % of dose excreted unchanged
Interval 15.0 to 36.2
|
—
|
22.33 % of dose excreted unchanged
Interval 2.93 to 54.3
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ERT- 4-8 h
|
15.92 % of dose excreted unchanged
Interval 7.42 to 26.8
|
13.78 % of dose excreted unchanged
Interval 5.27 to 20.7
|
—
|
10.14 % of dose excreted unchanged
Interval 8.14 to 13.6
|
23.77 % of dose excreted unchanged
Interval 13.1 to 61.6
|
—
|
20.16 % of dose excreted unchanged
Interval 8.18 to 46.2
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ZID - 0-4 h
|
54.48 % of dose excreted unchanged
Interval 25.9 to 81.6
|
—
|
66.70 % of dose excreted unchanged
Interval 52.8 to 81.0
|
73.75 % of dose excreted unchanged
Interval 54.2 to 102.0
|
—
|
61.25 % of dose excreted unchanged
Interval 42.2 to 70.4
|
45.58 % of dose excreted unchanged
Interval 8.26 to 69.4
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ERT- 8-12 h
|
6.43 % of dose excreted unchanged
Interval 1.98 to 8.38
|
6.12 % of dose excreted unchanged
Interval 2.94 to 10.2
|
—
|
6.45 % of dose excreted unchanged
Interval 3.88 to 10.1
|
5.79 % of dose excreted unchanged
Interval 4.28 to 7.57
|
—
|
6.41 % of dose excreted unchanged
Interval 3.74 to 10.2
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ERT- 12-24 h
|
4.98 % of dose excreted unchanged
Interval 2.56 to 6.65
|
4.21 % of dose excreted unchanged
Interval 2.49 to 7.48
|
—
|
2.72 % of dose excreted unchanged
Interval 0.96 to 5.32
|
4.97 % of dose excreted unchanged
Interval 2.82 to 7.83
|
—
|
3.57 % of dose excreted unchanged
Interval 1.95 to 5.28
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ZID - 4-8 h
|
15.06 % of dose excreted unchanged
Interval 6.26 to 27.7
|
—
|
17.98 % of dose excreted unchanged
Interval 12.5 to 27.6
|
12.96 % of dose excreted unchanged
Interval 7.45 to 15.7
|
—
|
21.07 % of dose excreted unchanged
Interval 10.8 to 27.0
|
33.55 % of dose excreted unchanged
Interval 17.6 to 86.8
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ZID - 8-12 h
|
3.33 % of dose excreted unchanged
Interval 0.69 to 5.13
|
—
|
4.02 % of dose excreted unchanged
Interval 2.84 to 8.11
|
4.18 % of dose excreted unchanged
Interval 1.91 to 6.13
|
—
|
4.77 % of dose excreted unchanged
Interval 3.45 to 8.46
|
5.60 % of dose excreted unchanged
Interval 4.22 to 7.22
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 1
Unchanged ZID - 12-24 h
|
1.99 % of dose excreted unchanged
Interval 1.33 to 2.43
|
—
|
1.35 % of dose excreted unchanged
Interval 0.76 to 2.7
|
1.27 % of dose excreted unchanged
Interval 0.9 to 1.85
|
—
|
2.51 % of dose excreted unchanged
Interval 1.25 to 3.65
|
2.53 % of dose excreted unchanged
Interval 0.72 to 5.86
|
—
|
SECONDARY outcome
Timeframe: 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine from zero (predose) to 24 h following Dose 1, fe,urine(0-24) (%), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24))
Unchanged ERT
|
59.40 % of dose excreted unchanged
Interval 20.4 to 85.6
|
54.32 % of dose excreted unchanged
Interval 16.1 to 74.7
|
—
|
58.98 % of dose excreted unchanged
Interval 35.5 to 109.0
|
55.85 % of dose excreted unchanged
Interval 40.1 to 71.8
|
—
|
52.43 % of dose excreted unchanged
Interval 28.1 to 79.9
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 1 (fe,Urine(0-24))
Unchanged ZID
|
73.32 % of dose excreted unchanged
Interval 37.0 to 92.2
|
—
|
89.82 % of dose excreted unchanged
Interval 73.3 to 97.9
|
91.75 % of dose excreted unchanged
Interval 70.9 to 121.0
|
—
|
89.58 % of dose excreted unchanged
Interval 60.6 to 103.0
|
87.32 % of dose excreted unchanged
Interval 34.5 to 106.0
|
—
|
SECONDARY outcome
Timeframe: 0-1 h pre-start of Dose 1 (Day 1) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 1 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of renal clearance of ERT and ZID from dosing until the last collected concentration for Dose 1 (24 h postdose), CLR(0-24) (mL/h ), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24))
Unchanged ERT
|
0.75 L/h
Geometric Coefficient of Variation 61
|
0.78 L/h
Geometric Coefficient of Variation 57
|
—
|
0.79 L/h
Geometric Coefficient of Variation 41
|
0.76 L/h
Geometric Coefficient of Variation 19
|
—
|
0.73 L/h
Geometric Coefficient of Variation 42
|
—
|
|
Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 1 (CLR(0-24))
Unchanged ZID
|
4.98 L/h
Geometric Coefficient of Variation 39
|
—
|
5.88 L/h
Geometric Coefficient of Variation 15
|
5.63 L/h
Geometric Coefficient of Variation 36
|
—
|
6.95 L/h
Geometric Coefficient of Variation 25
|
5.55 L/h
Geometric Coefficient of Variation 31
|
—
|
SECONDARY outcome
Timeframe: 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 (Day 7) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Mean and minimum/maximum of the amount of unchanged ERT and the amount of unchanged ZID excreted in urine, Ae,urine (mg), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 7 by dose group. Ae,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ERT - 4-8 h
|
113.37 mg
Interval 10.1 to 205.0
|
344.17 mg
Interval 132.0 to 911.0
|
—
|
234.94 mg
Interval 97.7 to 473.0
|
603.40 mg
Interval 186.0 to 1100.0
|
—
|
417.33 mg
Interval 209.0 to 727.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ERT - 8-12 h
|
54.95 mg
Interval 7.16 to 88.1
|
136.54 mg
Interval 21.7 to 198.0
|
—
|
88.86 mg
Interval 48.1 to 153.0
|
171.80 mg
Interval 137.0 to 217.0
|
—
|
113.88 mg
Interval 54.0 to 150.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ERT - 12-24 h
|
43.04 mg
Interval 26.7 to 68.2
|
29.69 mg
Interval 9.35 to 72.2
|
—
|
65.46 mg
Interval 55.0 to 81.1
|
113.98 mg
Interval 85.6 to 159.0
|
—
|
96.03 mg
Interval 61.5 to 167.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ZID - 0-4 h
|
624.50 mg
Interval 383.0 to 824.0
|
—
|
1210.33 mg
Interval 691.0 to 1570.0
|
1465.00 mg
Interval 1465.0 to 1640.0
|
—
|
1855.00 mg
Interval 1090.0 to 2200.0
|
1870.00 mg
Interval 1320.0 to 2280.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ZID - 8-12 h
|
27.93 mg
Interval 3.55 to 45.1
|
—
|
45.58 mg
Interval 23.1 to 55.4
|
62.98 mg
Interval 40.2 to 93.6
|
—
|
175.00 mg
Interval 138.0 to 212.0
|
113.78 mg
Interval 27.7 to 160.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ERT - 0-4 h
|
357.83 mg
Interval 208.0 to 525.0
|
702.30 mg
Interval 39.5 to 1270.0
|
—
|
777.80 mg
Interval 433.0 to 1490.0
|
1010.40 mg
Interval 655.0 to 1530.0
|
—
|
998.17 mg
Interval 467.0 to 1670.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ZID - 4-8 h
|
110.20 mg
Interval 7.22 to 173.0
|
—
|
302.00 mg
Interval 302.0 to 302.0
|
246.00 mg
Interval 219.0 to 307.0
|
—
|
556.83 mg
Interval 403.0 to 689.0
|
654.33 mg
Interval 253.0 to 1170.0
|
—
|
|
Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine (Ae,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ZID - 12-24 h
|
14.75 mg
Interval 7.36 to 25.4
|
—
|
62.37 mg
Interval 18.7 to 124.0
|
32.48 mg
Interval 13.3 to 44.8
|
—
|
67.67 mg
Interval 45.3 to 84.2
|
59.50 mg
Interval 34.0 to 85.6
|
—
|
SECONDARY outcome
Timeframe: 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Mean and minimum/maximum of the cumulative amount of unchanged ERT and the cumulative amount of unchanged ZID excreted in urine from zero (predose) to 24 h following Dose 7, Ae,urine(0-24) (mg), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS)
Unchanged ERT
|
552.83 mg
Interval 325.0 to 778.0
|
1067.33 mg
Interval 340.0 to 1700.0
|
—
|
1166 mg
Interval 652.0 to 2200.0
|
1898.00 mg
Interval 1060.0 to 3000.0
|
—
|
1624.50 mg
Interval 887.0 to 2320.0
|
—
|
|
Cumulative Amounts of Unchanged ERT and Unchanged ZID Excreted in Urine From Zero (Predose) to 24 h Following Dose 7 (Ae,Urine(0-24),SS)
Unchanged ZID
|
770.17 mg
Interval 495.0 to 1030.0
|
—
|
1080.00 mg
Interval 1080.0 to 1080.0
|
1808.33 mg
Interval 1580.0 to 1970.0
|
—
|
2656.67 mg
Interval 1770.0 to 2930.0
|
2700.00 mg
Interval 2200.0 to 3070.0
|
—
|
SECONDARY outcome
Timeframe: 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 (Day 7) infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine, fe,urine (%), during 0-4 h, 4-8 h, 8-12 h, and 12-24 h following Dose 7 by dose group. These fe,urine parameters are calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ERT - 0-4 h
|
35.78 % of dose excreted unchanged
Interval 20.8 to 52.5
|
35.09 % of dose excreted unchanged
Interval 1.97 to 63.3
|
—
|
38.94 % of dose excreted unchanged
Interval 21.7 to 74.6
|
33.68 % of dose excreted unchanged
Interval 21.8 to 51.0
|
—
|
33.28 % of dose excreted unchanged
Interval 15.6 to 55.8
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ERT - 4-8 h
|
11.34 % of dose excreted unchanged
Interval 1.01 to 20.5
|
17.19 % of dose excreted unchanged
Interval 6.62 to 45.5
|
—
|
11.72 % of dose excreted unchanged
Interval 4.89 to 23.6
|
20.08 % of dose excreted unchanged
Interval 6.19 to 36.5
|
—
|
13.91 % of dose excreted unchanged
Interval 6.96 to 24.2
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ERT - 8-12 h
|
5.50 % of dose excreted unchanged
Interval 0.72 to 8.81
|
6.83 % of dose excreted unchanged
Interval 1.08 to 9.91
|
—
|
4.45 % of dose excreted unchanged
Interval 2.41 to 7.67
|
5.73 % of dose excreted unchanged
Interval 4.57 to 7.23
|
—
|
3.80 % of dose excreted unchanged
Interval 1.8 to 5.01
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ZID - 0-4 h
|
62.45 % of dose excreted unchanged
Interval 38.3 to 82.4
|
—
|
60.40 % of dose excreted unchanged
Interval 34.5 to 78.4
|
73.27 % of dose excreted unchanged
Interval 62.6 to 82.1
|
—
|
61.85 % of dose excreted unchanged
Interval 36.4 to 73.4
|
62.38 % of dose excreted unchanged
Interval 44.0 to 76.0
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ZID - 4-8 h
|
11.02 % of dose excreted unchanged
Interval 0.72 to 17.3
|
—
|
15.10 % of dose excreted unchanged
Interval 15.1 to 15.1
|
12.28 % of dose excreted unchanged
Interval 11.0 to 15.3
|
—
|
18.55 % of dose excreted unchanged
Interval 13.4 to 23.0
|
21.84 % of dose excreted unchanged
Interval 8.43 to 39.1
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ZID - 12-24 h
|
1.48 % of dose excreted unchanged
Interval 0.74 to 2.54
|
—
|
3.12 % of dose excreted unchanged
Interval 0.93 to 6.2
|
1.63 % of dose excreted unchanged
Interval 0.67 to 2.24
|
—
|
2.26 % of dose excreted unchanged
Interval 1.51 to 2.81
|
1.98 % of dose excreted unchanged
Interval 1.13 to 2.85
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ERT - 12-24 h
|
4.30 % of dose excreted unchanged
Interval 2.67 to 6.82
|
1.48 % of dose excreted unchanged
Interval 0.47 to 3.61
|
—
|
3.27 % of dose excreted unchanged
Interval 2.75 to 4.06
|
3.80 % of dose excreted unchanged
Interval 2.85 to 5.3
|
—
|
3.20 % of dose excreted unchanged
Interval 2.05 to 5.56
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine (fe,Urine) During Each Nominal Time Collection Interval Following Dose 7
Unchanged ZID - 8-12 h
|
2.79 % of dose excreted unchanged
Interval 0.36 to 4.51
|
—
|
2.28 % of dose excreted unchanged
Interval 1.16 to 2.77
|
3.15 % of dose excreted unchanged
Interval 2.01 to 4.68
|
—
|
5.84 % of dose excreted unchanged
Interval 4.61 to 7.05
|
3.79 % of dose excreted unchanged
Interval 0.92 to 5.34
|
—
|
SECONDARY outcome
Timeframe: 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Mean and minimum/maximum of the fraction of ERT and the fraction of ZID excreted unchanged in urine from zero (predose) to 24 h following Dose 7, fe,urine(0-24) (%), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS)
Unchanged ERT
|
55.28 % of dose excreted unchanged
Interval 32.5 to 77.8
|
53.35 % of dose excreted unchanged
Interval 17.0 to 84.9
|
—
|
58.36 % of dose excreted unchanged
Interval 32.6 to 110.0
|
63.28 % of dose excreted unchanged
Interval 35.5 to 100.0
|
—
|
54.20 % of dose excreted unchanged
Interval 29.6 to 77.4
|
—
|
|
Fractions (%) of ERT and ZID Excreted Unchanged in Urine From Zero (Predose) to 24 h Following Dose 7 (fe,Urine(0-24),SS)
Unchanged ZID
|
77.02 % of dose excreted unchanged
Interval 49.5 to 103.0
|
—
|
53.80 % of dose excreted unchanged
Interval 53.8 to 53.8
|
90.35 % of dose excreted unchanged
Interval 78.8 to 98.5
|
—
|
88.48 % of dose excreted unchanged
Interval 59.0 to 97.5
|
89.93 % of dose excreted unchanged
Interval 73.3 to 102.0
|
—
|
SECONDARY outcome
Timeframe: 0-1 h pre-start of Dose 7 (Day 7) infusion and 0-4 h, 4-8 h, 8-12 h, and 12-24 h post-start of Dose 7 infusionPopulation: PK Analysis Subset Population: all participants who received the intended dose of study drug(s) on the given day(s) of analysis, have at least one quantifiable post-dosing plasma drug concentration measured, and have sufficient data that permit estimation of PK parameters. Any participant with at least one estimable PK parameter is included in this subset.
Geometric mean (GM), and coefficient of variation percentage (CV%) of renal clearance of ERT and ZID from dosing until the last collected concentration for Dose 7 (24 h postdose), CLR(0-24) (mL/h), by dose group. This parameter is calculated using a combination of Phoenix WinNonlin and SAS version 9.4 or above.
Outcome measures
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 Participants
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 Participants
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 Participants
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 Participants
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=5 Participants
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 Participants
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 Participants
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS)
Unchanged ERT
|
0.74 L/h
Geometric Coefficient of Variation 28
|
0.78 L/h
Geometric Coefficient of Variation 53
|
—
|
0.84 L/h
Geometric Coefficient of Variation 48
|
0.92 L/h
Geometric Coefficient of Variation 37
|
—
|
0.9 L/h
Geometric Coefficient of Variation 44
|
—
|
|
Renal Clearance of ERT and ZID From Dosing Until the Last Collected Concentration for Dose 7 (CLR(0-24),SS)
Unchanged ZID
|
5.59 L/h
Geometric Coefficient of Variation 35
|
—
|
4.68 L/h
Geometric Coefficient of Variation NA
Cannot be calculated as data only available for one participant
|
5.84 L/h
Geometric Coefficient of Variation 25
|
—
|
6.8 L/h
Geometric Coefficient of Variation 25
|
6.77 L/h
Geometric Coefficient of Variation 12
|
—
|
Adverse Events
Cohort 1 - WCK 6777 2 g
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 2 - ERT 2 g
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 3 - ZID 2 g
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Cohort 4 - WCK 6777 4 g
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Cohort 5 - ERT 3 g
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort 6 - ZID 3 g
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 7 - WCK 6777 6 g
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1 - WCK 6777 2 g
n=6 participants at risk
WCK 6777 (Ertapenem 1 g combined with Zidebactam 1 g) administered by 100 ml of intravenous infusion (IV) for 30 (±5) minutes once daily for 7 days.
|
Cohort 2 - ERT 2 g
n=6 participants at risk
Ertapenem 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour once daily for 7 days.
|
Cohort 3 - ZID 2 g
n=6 participants at risk
Zidebactam 2 g administered by 250 ml of intravenous infusion (IV) for 1 hour,once daily,for 7 days.
|
Cohort 4 - WCK 6777 4 g
n=6 participants at risk
WCK 6777 (Ertapenem 2 g combined with Zidebactam 2 g) administered by 250 ml of intravenous infusion (IV) for 1 hour, once daily, for 7 days.
|
Cohort 5 - ERT 3 g
n=6 participants at risk
Ertapenem 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 6 - ZID 3 g
n=6 participants at risk
Zidebactam 3 g administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Cohort 7 - WCK 6777 6 g
n=6 participants at risk
WCK 6777 (Ertapenem 3 g combined with Zidebactam 3 g) administered by 250 ml of intravenous infusion (IV) for 2 hours, once daily, for 7 days.
|
Placebo
n=10 participants at risk
Placebo participants from Cohorts 1,2,4,5,7. Placebo administered corresponding to method for active drug administration in each cohort.
|
|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
10.0%
1/10 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
33.3%
2/6 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Gastrointestinal disorders
Nausea
|
33.3%
2/6 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
10.0%
1/10 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site erythema
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
33.3%
2/6 • Number of events 5 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
50.0%
3/6 • Number of events 3 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
33.3%
2/6 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
10.0%
1/10 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site extravasation
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
33.3%
2/6 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
33.3%
2/6 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
30.0%
3/10 • Number of events 4 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site haemorrhage
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
30.0%
3/10 • Number of events 5 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site oedema
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
10.0%
1/10 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site pain
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
33.3%
2/6 • Number of events 4 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site papule
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site phlebitis
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
10.0%
1/10 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site pruritus
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Infusion site swelling
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
20.0%
2/10 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Injection site haemorrhage
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
33.3%
2/6 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Injection site phlebitis
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Pyrexia
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Vessel puncture site bruise
|
16.7%
1/6 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Vessel puncture site pain
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
General disorders
Vessel puncture site phlebitis
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Infections and infestations
Viral infection
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Injury, poisoning and procedural complications
Wound
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Investigations
Blood pressure increased
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Investigations
Blood pressure systolic increased
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
10.0%
1/10 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Investigations
Body temperature increased
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
20.0%
2/10 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Investigations
Heart rate decreased
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
20.0%
2/10 • Number of events 2 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
10.0%
1/10 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
16.7%
1/6 • Number of events 1 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/6 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
0.00%
0/10 • AEs were documented from the time of starting study drug administration through the time of Final Visit (Day 11 + 3 days)
|
Additional Information
George Saviolakis
DynPort Vaccine Company, a GDIT Company
Phone: 301-835-4101
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60