Trial Outcomes & Findings for Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) in Japanese Participants With Complicated Intra-abdominal Infection or Complicated Urinary Tract Infection (MK-7655A-017) (NCT NCT03293485)

Last Updated: 2021-02-12

Results Overview

The percentage of participants experiencing ≥1 AE was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

83 participants

Primary outcome timeframe

Up to 28 days

Results posted on

2021-02-12

Participant Flow

Participant milestones

Participant milestones
Measure	cIAI/cUTI Participants with complicated intra-abdominal infection (cIAI) or complicated urinary tract infection (cUTI) received intravenous imipenem+cilastatin+relebactam (IMI/REL) once every 6 hours for 5-14 days.
Overall Study STARTED	83
Overall Study Treated	81
Overall Study COMPLETED	78
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	cIAI/cUTI Participants with complicated intra-abdominal infection (cIAI) or complicated urinary tract infection (cUTI) received intravenous imipenem+cilastatin+relebactam (IMI/REL) once every 6 hours for 5-14 days.
Overall Study Death	1
Overall Study Screen Failure	2
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) in Japanese Participants With Complicated Intra-abdominal Infection or Complicated Urinary Tract Infection (MK-7655A-017)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	cIAI/cUTI n=83 Participants Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Age, Continuous	62.8 Years STANDARD_DEVIATION 18.2 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	83 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	83 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Infection Type cIAI	39 Participants n=5 Participants
Infection Type cUTI	44 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 28 days

Population: Per protocol, the population analyzed was all participants who received ≥1 dose of intravenous imipenem+cilastatin+relebactam.

Outcome measures

Outcome measures
Measure	cIAI/cUTI n=81 Participants Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Percentage of Participants Experiencing ≥1 Adverse Events (AE)	74.1 Percentage of Participants Interval 63.5 to 82.4

PRIMARY outcome

Timeframe: Up to 14 days (End of Therapy Visit)

Population: Per protocol, the population analyzed was all participants who received ≥1 dose of intravenous imipenem+cilastatin+relebactam.

The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Outcome measures

Outcome measures
Measure	cIAI/cUTI n=81 Participants Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	4.9 Percentage of Participants Interval 1.6 to 12.4

PRIMARY outcome

Timeframe: Between Day 5 and Day 14 (End of Therapy Visit)

Population: Per protocol, the population analyzed was all participants with cIAI who received intravenous imipenem+cilastatin+relebactam ≥96 hours, whose pre-study infection-site culture grew ≥1 gram-negative enteric and/or anaerobic pathogen, and who had no major deviations from the protocol that may substantially affect the results of the efficacy analyses.

The percentage of participants with cIAI who display a favorable clinical response at End of Therapy visit was presented. Per protocol, a subset of the cIAI/cUTI study arm was analyzed: only participants with cIAI were evaluated because clinical response is primarily relevant to cIAI. Favorable clinical response is a rating of "cure" or "improved" as determined by the investigator at the End of Therapy Visit. "Cure" is defined as: all pretherapy signs and symptoms of the index infection(s) have resolved (or returned to preinfection status) AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed. "Improved" is defined as: All or most pretherapy signs and symptoms of the index infection(s) have improved or resolved (or returned to preinfection status) AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed.

Outcome measures

Outcome measures
Measure	cIAI/cUTI n=28 Participants Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at End of Therapy Visit	85.7 Percentage of Participants Interval 67.9 to 94.9

PRIMARY outcome

Timeframe: Between Day 5 and Day 14 (End of Therapy Visit)

Population: Per protocol, the population analyzed was all participants with cUTI who received intravenous imipenem+cilastatin+relebactam ≥96 hours, whose pre-study infection-site culture grew ≥1 gram-negative and/or anaerobic pathogen, and who had no major deviations from the protocol that may substantially affect the results of the efficacy analyses.

The percentage of participants with cUTI who display a favorable Overall Microbiological Response at the End of Therapy visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cUTI were evaluated because the microbiological response evaluation is primarily relevant to cUTI. A favorable Overall Microbiological Response is defined as a urine culture taken at the End of Therapy Visit showing eradication (e.g., ≥10\^5 CFU/mL is reduced to \<10\^4 CFU/mL) of all uropathogens found at study entry.

Outcome measures

Outcome measures
Measure	cIAI/cUTI n=39 Participants Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at End of Therapy Visit	100 Percentage of Participants Interval 89.3 to 100.0

SECONDARY outcome

Timeframe: Between Day 10 and Day 23 (Test of Cure Visit)

The percentage of participants with cIAI who display a favorable Clinical Response at the Test of Cure visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cIAI were evaluated because the clinical response evaluation is primarily relevant to cIAI. A favorable clinical response is a rating of "cure" as determined by the investigator at the Test of Cure Visit. "Cure" is defined as: all pretherapy signs and symptoms of the index infection(s) have resolved (or returned to "preinfection status") AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed.

Outcome measures

Outcome measures
Measure	cIAI/cUTI n=28 Participants Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at Test of Cure Visit	82.1 Percentage of Participants Interval 63.9 to 92.6

SECONDARY outcome

Timeframe: Between Day 10 and Day 23 (Test of Cure Visit)

The percentage of participants with cUTI who display a favorable Overall Microbiological Response at the Test of Cure visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cUTI were evaluated because the microbiological response evaluation is primarily relevant to cUTI. A favorable Overall Microbiological Response is defined as a urine culture taken at the Test of Cure visit still showing eradication (e.g., ≥10\^5 CFU/mL is reduced to \<10\^4 CFU/mL) of all uropathogens found at study entry.

Outcome measures

Outcome measures
Measure	cIAI/cUTI n=39 Participants Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at Test of Cure Visit	59.0 Percentage of Participants Interval 43.4 to 72.9

Adverse Events

cIAI/cUTI

Serious events: 9 serious events

Other events: 18 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	cIAI/cUTI n=81 participants at risk Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Eye disorders Rhegmatogenous retinal detachment	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Gastrointestinal disorders Large intestine perforation	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Gastrointestinal disorders Pancreatitis acute	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Hepatobiliary disorders Cholecystitis acute	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Infections and infestations Abdominal abscess	2.5% 2/81 • Number of events 2 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Infections and infestations Pelvic abscess	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Infections and infestations Peritonitis	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Injury, poisoning and procedural complications Postoperative ileus	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Renal and urinary disorders Acute kidney injury	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Renal and urinary disorders Renal haematoma	1.2% 1/81 • Number of events 1 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.

Other adverse events

Other adverse events
Measure	cIAI/cUTI n=81 participants at risk Participants with cIAI or cUTI received intravenous imipenem+cilastatin+relebactam once every 6 hours for 5-14 days.
Gastrointestinal disorders Diarrhoea	8.6% 7/81 • Number of events 7 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Gastrointestinal disorders Nausea	8.6% 7/81 • Number of events 9 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.
Infections and infestations Nasopharyngitis	6.2% 5/81 • Number of events 5 • Up to 28 days (up to 14 days after completion of intravenous study therapy) Adverse events were reported for all participants who received at least one dose of IV study therapy.

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 Subsequent to the multicenter publication (or after public disclosure of the results at www.clinicaltrials.gov if multicenter manuscript is not planned), an investigator and colleagues may publish their data independently. Sponsor must have opportunity to review proposed abstracts, manuscripts or presentations 45 days prior to submission for publication/presentation. Confidential information must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Publication restrictions are in place

Restriction type: OTHER