Trial Outcomes & Findings for Safety, Tolerability, and Efficacy of MK-7655 (Relebactam) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone for Treating Complicated Urinary Tract Infection (cUTI) (MK-7655-003) (NCT NCT01505634)
NCT ID: NCT01505634
Last Updated: 2019-05-24
Results Overview
Microbiological response (MR) was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
302 participants
Primary outcome timeframe
At time of last IV dose of study drug (up to post-randomization day 14)
Results posted on
2019-05-24
Participant Flow
Participants were enrolled with complicated urinary tract infection (cUTI) or acute pyelonephritis judged by the investigator to be serious (requiring hospitalization and intravenous (IV) antibiotic therapy); pyuria; and 1 positive urine culture within 48 hours of enrollment.
Participant milestones
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
101
|
101
|
100
|
|
Overall Study
Treated
|
99
|
99
|
100
|
|
Overall Study
COMPLETED
|
92
|
91
|
94
|
|
Overall Study
NOT COMPLETED
|
9
|
10
|
6
|
Reasons for withdrawal
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
5
|
1
|
|
Overall Study
Physician Decision
|
1
|
1
|
0
|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
|
Overall Study
Insufficient supply of drug at site
|
1
|
0
|
0
|
|
Overall Study
Protocol Violation
|
2
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
4
|
4
|
|
Overall Study
Death
|
1
|
0
|
0
|
|
Overall Study
In a conflict zone
|
0
|
0
|
1
|
Baseline Characteristics
Safety, Tolerability, and Efficacy of MK-7655 (Relebactam) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone for Treating Complicated Urinary Tract Infection (cUTI) (MK-7655-003)
Baseline characteristics by cohort
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=101 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=101 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Total
n=302 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57.9 Years
STANDARD_DEVIATION 17.3 • n=93 Participants
|
55.9 Years
STANDARD_DEVIATION 17.5 • n=4 Participants
|
55.7 Years
STANDARD_DEVIATION 19.2 • n=27 Participants
|
56.5 Years
STANDARD_DEVIATION 18.0 • n=483 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=93 Participants
|
60 Participants
n=4 Participants
|
42 Participants
n=27 Participants
|
153 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=93 Participants
|
41 Participants
n=4 Participants
|
58 Participants
n=27 Participants
|
149 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: At time of last IV dose of study drug (up to post-randomization day 14)Population: All participants in the ME population with non-missing/non-indeterminate response.
Microbiological response (MR) was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=67 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=71 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=75 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy
|
95.5 Percentage of Participants
Interval 87.5 to 99.1
|
98.6 Percentage of Participants
Interval 92.4 to 100.0
|
98.7 Percentage of Participants
Interval 92.8 to 100.0
|
PRIMARY outcome
Timeframe: Up to 14 days following completion of all study therapy (up to 28 days)Population: All randomized participants who received ≥ 1 dose of study treatment.
All randomized participants who received ≥1 dose of study treatment had AST and ALT levels measured up to 14 days following completion of all study medication. Participants who had 2 confirmed elevations of either AST or ALT that were 5 times ULN or greater were recorded.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Value That Was Greater Than or Equal to 5 Times the Upper Limit of Normal (ULN)
|
1.0 Percentage of participants
|
1.0 Percentage of participants
|
0 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 14 days following completion of all study therapy (up to 28 days)Population: All randomized participants who received ≥ 1 dose of study treatment.
All randomized participants who received ≥1 dose of study treatment had AST, ALT, total bilirubin, and Alkaline Phosphatase (ALP) levels measured up to 14 days following completion of all study medication. Participants who had elevations of AST or ALT that were ≥3 times ULN, total bilirubin measurements that were ≥2 times ULN and, at the same time, an ALP measurement of \< 2X ULN were recorded.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With Elevated AST or ALT Laboratory Values ≥ 3 Times the ULN, as Well as Elevated Total Bilirubin ≥ 2 Times the ULN, and Alkaline Phosphatase Values That Were < 2 Times the ULN
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 14 days following completion of all study therapy (up to 28 days)Population: All randomized participants who received ≥1 dose of study treatment.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With at Least 1 Adverse Event (AE)
|
28.3 Percentage of participants
|
29.3 Percentage of participants
|
30.0 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 14 days following completion of all study therapy (up to 28 days)Population: All randomized participants who received ≥1 dose of study treatment.
A SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With Any Serious Adverse Event (SAE)
|
3.0 Percentage of participants
|
1.0 Percentage of participants
|
3.0 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 14 days following completion of all study therapy (up to 28 days)Population: All randomized participants who received ≥1 dose of study treatment.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related (DR) AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With Any Drug-related AE
|
10.1 Percentage of participants
|
9.1 Percentage of participants
|
9.0 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 42 days following completion of all study therapy (up to 56 days)Population: All randomized participants who received ≥1 dose of study treatment.
A serious, drug-related (DR) AE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The SAE was determined to be possibly, probably, or definitely related to the treatment by the investigator.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With a Drug-related SAE
|
1.0 Percentage of participants
|
0 Percentage of participants
|
1.0 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 14 daysPopulation: All randomized participants who received ≥1 dose of study treatment.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a pre-existing condition temporally associated with the use of the product was also an AE.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants Who Discontinued IV Study Therapy Due to an AE
|
3.0 Percentage of participants
|
1.0 Percentage of participants
|
2.0 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 14 daysPopulation: All randomized participants who received ≥1 dose of study treatment.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE
|
2.0 Percentage of participants
|
1.0 Percentage of participants
|
1.0 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 14 days following completion of all study therapy (up to 28 days)Population: All randomized participants who received ≥1 dose of study treatment.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. Analysis includes specific adverse events with an incidence of ≥4 participants in one treatment group or system organ class.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
Headache
|
7.1 Percentage of participants
|
3.0 Percentage of participants
|
4.0 Percentage of participants
|
|
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
Diarrhoea
|
5.1 Percentage of participants
|
2.0 Percentage of participants
|
4.0 Percentage of participants
|
|
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
Nausea
|
4.0 Percentage of participants
|
6.1 Percentage of participants
|
4.0 Percentage of participants
|
|
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
Bacteriuria
|
1.0 Percentage of participants
|
2.0 Percentage of participants
|
4.0 Percentage of participants
|
|
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
White blood cells urine positive
|
1.0 Percentage of participants
|
1.0 Percentage of participants
|
4.0 Percentage of participants
|
SECONDARY outcome
Timeframe: At time of last IV dose of study drug (up to post-randomization day 14)Population: All participants in the ME population with imipenem-resistant gram-negative infections at baseline.
Microbiological response was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for imipenem-resistant gram-negative or anaerobic infections at baseline. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=10 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=7 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=6 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy Who Had Imipenem-resistant, Gram-negative cUTI Infections.
|
100.0 Percentage of participants
Interval 69.2 to 100.0
|
100.0 Percentage of participants
Interval 59.0 to 100.0
|
100.0 Percentage of participants
Interval 54.1 to 100.0
|
SECONDARY outcome
Timeframe: Up to 9 days following completion of all study IV and oral therapy (up to Day 23)Population: All participants in the ME population with non-missing/non-indeterminate response.
Microbiological response was assessed based on results of bacterial cultures obtained up to 9 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=65 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=72 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=71 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With a Favorable Microbiological Response at Early Follow-up
|
61.5 Percentage of participants
Interval 48.6 to 73.3
|
68.1 Percentage of participants
Interval 56.0 to 78.6
|
70.4 Percentage of participants
Interval 58.4 to 80.7
|
SECONDARY outcome
Timeframe: At time of last IV dose of study drug (up to postrandomization day 14)Population: All participants in the ME population with non-missing/nonindeterminate response.
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=69 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=78 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=80 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy
|
97.1 Percentage of participants
Interval 89.9 to 99.6
|
98.7 Percentage of participants
Interval 93.1 to 100.0
|
98.8 Percentage of participants
Interval 93.2 to 100.0
|
SECONDARY outcome
Timeframe: Up to 9 days following completion of all study IV and oral therapy (up to Day 23)Population: All participants in the ME population with non-missing/non-indeterminate response.
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=64 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=73 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=76 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With a Favorable Clinical Response at Early Follow-up
|
89.1 Percentage of Participants
Interval 78.8 to 95.5
|
91.8 Percentage of Participants
Interval 83.0 to 96.9
|
93.4 Percentage of Participants
Interval 85.3 to 97.8
|
SECONDARY outcome
Timeframe: Up to 42 days following completion of all study IV and oral therapy (up to Day 56)Population: All participants in the ME population with non-missing/non-indeterminate response.
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=62 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=71 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=76 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With a Favorable Clinical Response at Late Follow-up
|
88.7 Percentage of participants
Interval 78.1 to 95.3
|
87.3 Percentage of participants
Interval 77.3 to 94.0
|
88.2 Percentage of participants
Interval 78.7 to 94.4
|
SECONDARY outcome
Timeframe: Up to 42 days following completion of all study IV and oral therapy (up to Day 56)Population: All participants in the ME population with non-missing/non-indeterminate response.
Microbiological response was assessed based on results of bacterial cultures obtained up to 42 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Outcome measures
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=63 Participants
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=69 Participants
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=72 Participants
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Percentage of Participants With a Favorable Microbiological Response at Late Follow-up
|
68.3 Percentage of participants
Interval 55.3 to 79.4
|
65.2 Percentage of participants
Interval 52.8 to 76.3
|
62.5 Percentage of participants
Interval 50.3 to 73.6
|
Adverse Events
Relebactam 250 mg With Imipenem/Cilastatin
Serious events: 5 serious events
Other events: 11 other events
Deaths: 2 deaths
Relebactam 125 mg With Imipenem/Cilastatin
Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths
Relebactam Placebo With Imipenem/Cilastatin
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 participants at risk
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 participants at risk
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 participants at risk
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Cardiac disorders
Cardiac arrest
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
1.0%
1/100 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Gastrointestinal disorders
Duodenal ulcer
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Gastrointestinal disorders
Duodenal ulcer perforation
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
1.0%
1/100 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Renal and urinary disorders
Glomerulonephritis rapidly progressive
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
1.0%
1/100 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Infections and infestations
Peritonitis
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Infections and infestations
Pyelonephritis acute
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Infections and infestations
Urosepsis
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Injury, poisoning and procedural complications
Postoperative wound complication
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
|
1.0%
1/99 • Number of events 1 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/99 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
0.00%
0/100 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
Other adverse events
| Measure |
Relebactam 250 mg With Imipenem/Cilastatin
n=99 participants at risk
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam 125 mg With Imipenem/Cilastatin
n=99 participants at risk
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
Relebactam Placebo With Imipenem/Cilastatin
n=100 participants at risk
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
7.1%
7/99 • Number of events 7 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
3.0%
3/99 • Number of events 3 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
4.0%
4/100 • Number of events 4 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
|
Gastrointestinal disorders
Nausea
|
4.0%
4/99 • Number of events 4 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
6.1%
6/99 • Number of events 6 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
4.0%
4/100 • Number of events 5 • Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).
AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment. All-Cause Mortality included deaths outside the 14 day follow up period.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
- Publication restrictions are in place
Restriction type: OTHER