Last reviewed · How we verify

NCT01505634

Safety, Tolerability, and Efficacy of MK-7655 (Relebactam) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone for Treating Complicated Urinary Tract Infection (cUTI) (MK-7655-003)

Completed Phase 2 Results posted Last updated 24 May 2019
What this trial tests

Phase 2 trial testing Relebactam 250 mg in Urinary Tract Infections in 302 participants. Completed in 28 July 2015.

Timeline
16 May 2012
Primary endpoint
28 July 2015
28 July 2015

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment302
Start date16 May 2012
Primary completion28 July 2015
Estimated completion28 July 2015

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Urinary Tract Infections or Pyelonephritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy Primary · At time of last IV dose of study drug (up to post-randomization day 14)

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 microbiolo

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin95.587.5 – 99.1
Relebactam 125 mg With Imipenem/Cilastatin98.692.4 – 100.0
Relebactam Placebo With Imipenem/Cilastatin98.792.8 – 100.0
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) Primary · Up to 14 days following completion of all study therapy (up to 28 days)

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.

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin1.0
Relebactam 125 mg With Imipenem/Cilastatin1.0
Relebactam Placebo With Imipenem/Cilastatin0
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 Primary · Up to 14 days following completion of all study therapy (up to 28 days)

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.

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin0
Relebactam 125 mg With Imipenem/Cilastatin0
Relebactam Placebo With Imipenem/Cilastatin0
Percentage of Participants With at Least 1 Adverse Event (AE) Primary · Up to 14 days following completion of all study therapy (up to 28 days)

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.

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin28.3
Relebactam 125 mg With Imipenem/Cilastatin29.3
Relebactam Placebo With Imipenem/Cilastatin30.0
Percentage of Participants With Any Serious Adverse Event (SAE) Primary · Up to 14 days following completion of all study therapy (up to 28 days)

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.

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin3.0
Relebactam 125 mg With Imipenem/Cilastatin1.0
Relebactam Placebo With Imipenem/Cilastatin3.0
Percentage of Participants With Any Drug-related AE Primary · Up to 14 days following completion of all study therapy (up to 28 days)

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 an

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin10.1
Relebactam 125 mg With Imipenem/Cilastatin9.1
Relebactam Placebo With Imipenem/Cilastatin9.0
Percentage of Participants With a Drug-related SAE Primary · Up to 42 days following completion of all study therapy (up to 56 days)

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.

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin1.0
Relebactam 125 mg With Imipenem/Cilastatin0
Relebactam Placebo With Imipenem/Cilastatin1.0
Percentage of Participants Who Discontinued IV Study Therapy Due to an AE Primary · Up to 14 days

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.

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin3.0
Relebactam 125 mg With Imipenem/Cilastatin1.0
Relebactam Placebo With Imipenem/Cilastatin2.0
Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE Primary · Up to 14 days

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 unt

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin2.0
Relebactam 125 mg With Imipenem/Cilastatin1.0
Relebactam Placebo With Imipenem/Cilastatin1.0
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group Primary · Up to 14 days following completion of all study therapy (up to 28 days)

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 event

Diarrhoea
GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin5.1
Relebactam 125 mg With Imipenem/Cilastatin2.0
Relebactam Placebo With Imipenem/Cilastatin4.0
Nausea
GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin4.0
Relebactam 125 mg With Imipenem/Cilastatin6.1
Relebactam Placebo With Imipenem/Cilastatin4.0
Bacteriuria
GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin1.0
Relebactam 125 mg With Imipenem/Cilastatin2.0
Relebactam Placebo With Imipenem/Cilastatin4.0
White blood cells urine positive
GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin1.0
Relebactam 125 mg With Imipenem/Cilastatin1.0
Relebactam Placebo With Imipenem/Cilastatin4.0
Headache
GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin7.1
Relebactam 125 mg With Imipenem/Cilastatin3.0
Relebactam Placebo With Imipenem/Cilastatin4.0
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy Who Had Imipenem-resistant, Gram-negative cUTI Infections. Secondary · At time of last IV dose of study drug (up to post-randomization day 14)

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

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin100.069.2 – 100.0
Relebactam 125 mg With Imipenem/Cilastatin100.059.0 – 100.0
Relebactam Placebo With Imipenem/Cilastatin100.054.1 – 100.0
Percentage of Participants With a Favorable Microbiological Response at Early Follow-up Secondary · Up to 9 days following completion of all study IV and oral therapy (up to Day 23)

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 microbiolo

GroupValue95% CI
Relebactam 250 mg With Imipenem/Cilastatin61.548.6 – 73.3
Relebactam 125 mg With Imipenem/Cilastatin68.156.0 – 78.6
Relebactam Placebo With Imipenem/Cilastatin70.458.4 – 80.7

Adverse events — posted to ClinicalTrials.gov

Time frame: 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).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Relebactam 250 mg With Imipenem/Cilastatin
Serious: 5/99 (5%)
Deaths: 2/99
Relebactam 125 mg With Imipenem/Cilastatin
Serious: 2/99 (2%)
Deaths: 0/99
Relebactam Placebo With Imipenem/Cilastatin
Serious: 3/100 (3%)
Deaths: 0/100

Serious adverse events (12 terms)

ReactionSystemRelebactam 250 mg With Imi…Relebactam 125 mg With Imi…Relebactam Placebo With Im…
Cardiac arrestCardiac disorders———
DiarrhoeaGastrointestinal disorders———
Duodenal ulcerGastrointestinal disorders———
Duodenal ulcer perforationGastrointestinal disorders———
Intestinal obstructionGastrointestinal disorders———
Glomerulonephritis rapidly progressiveRenal and urinary disorders———
PeritonitisInfections and infestations———
Pyelonephritis acuteInfections and infestations———
UrosepsisInfections and infestations———
Postoperative wound complicationInjury, poisoning and procedural complications———
Renal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)———
Renal neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)———
Other adverse events (2 terms — click to expand)

ReactionSystemRelebactam 250 mg With Imi…Relebactam 125 mg With Imi…Relebactam Placebo With Im…
HeadacheNervous system disorders———
NauseaGastrointestinal disorders———

Most-reported serious reactions: Cardiac arrest, Diarrhoea, Duodenal ulcer, Duodenal ulcer perforation, Intestinal obstruction, Glomerulonephritis rapidly progressive, Peritonitis, Pyelonephritis acute.

Data from ClinicalTrials.gov NCT01505634 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125 mg or 250 mg doses of MK-7655 (relebactam) to imipenem/cilastatin in adults 18 years or older with complicated urinary tract infection (cUTI). The primary hypothesis is that the relebactam + imipenem/cilastatin treatment regimen is non-inferior to imipenem/cilastatin with respect to the proportion of participants with a favorable microbiological response at completion of intravenous (IV) study therapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Infections Caused by Carbapenem-Resistant <i>Enterobacteriaceae</i>: An Update on Therapeutic Options.
    Sheu CC, Chang YT, Lin SY, Chen YH, et al · · 2019 · cited 334× · PMID 30761114 · DOI 10.3389/fmicb.2019.00080
  2. New β-lactamase inhibitors: a therapeutic renaissance in an MDR world.
    Drawz SM, Papp-Wallace KM, Bonomo RA. · · 2014 · cited 199× · PMID 24379206 · DOI 10.1128/aac.00826-13
  3. New β-Lactamase Inhibitors in the Clinic.
    Papp-Wallace KM, Bonomo RA. · · 2016 · cited 121× · PMID 27208767 · DOI 10.1016/j.idc.2016.02.007
  4. Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections.
    Sims M, Mariyanovski V, McLeroth P, Akers W, et al · · 2017 · cited 120× · PMID 28575389 · DOI 10.1093/jac/dkx139
  5. <i>In Vitro</i> Activity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program).
    Lob SH, Hackel MA, Kazmierczak KM, Young K, et al · · 2017 · cited 102× · PMID 28320716 · DOI 10.1128/aac.02209-16
  6. Defining the Role of Novel β-Lactam Agents That Target Carbapenem-Resistant Gram-Negative Organisms.
    Tamma PD, Hsu AJ. · · 2019 · cited 55× · PMID 30793757 · DOI 10.1093/jpids/piz002
  7. Population Pharmacokinetic Analysis for Imipenem-Relebactam in Healthy Volunteers and Patients With Bacterial Infections.
    Bhagunde P, Patel P, Lala M, Watson K, et al · · 2019 · cited 41× · PMID 31508899 · DOI 10.1002/psp4.12462
  8. Exploring the Pharmacokinetic/Pharmacodynamic Relationship of Relebactam (MK-7655) in Combination with Imipenem in a Hollow-Fiber Infection Model.
    Wu J, Racine F, Wismer MK, Young K, et al · · 2018 · cited 40× · PMID 29507068 · DOI 10.1128/aac.02323-17

Verify or expand the search:

Other trials of Relebactam 250 mg

Trials testing the same drug.

Other recruiting trials for Urinary Tract Infections

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01505634.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing