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)

A Phase III Non-randomized, Non-controlled, Open Label Clinical Trial to Study the Safety and Efficacy of Imipenem/Cilastatin/Relebactam (IMI/REL [MK-7655A]) in Japanese Subjects With Complicated Intra-Abdominal Infection (cIAI) or Complicated Urinary Tract Infection (cUTI)

The study will evaluate the efficacy and safety of imipenem+cilastatin/relebactam (IMI/REL, MK-7655A) in Japanese participants with complicated intra-abdominal infection (cIAI) or complicated urinary tract infection (cUTI).

Study Overview

• Status: Completed
• Conditions: Complicated Intra-abdominal Infection; Complicated Urinary Tract Infection
• Intervention / Treatment: Drug: Imipenem+Cilastatin/Relebactam

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukui, Japan, 918-8503
    • Fukuiken Saiseikai Hospital ( Site 1704)
  • Fukuoka, Japan, 811-0213
    • Medical Corporation Chiyukai Fukuoka Wajiro Hospital ( Site 1709)
  • Kagoshima, Japan, 890-0073
    • Medical Corporation Shingenkai Kawahara Urological Clinic ( Site 1726)
  • Kagoshima, Japan, 891-0105
    • Medical Corporation Seifukai Yagi Clinic ( Site 1720)
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center ( Site 1713)
  • Oita, Japan, 870-0263
    • National Hospital Organization Oita Medical Center ( Site 1717)
  • Aichi
    • Nagoya, Aichi, Japan, 454-8502
      • Nagoya Ekisaikai Hospital ( Site 1724)
    • Toyota, Aichi, Japan, 471-8513
      • Toyota Memorial Hospital ( Site 1708)
  • Fukuoka
    • Onga-gun, Fukuoka, Japan, 807-0051
      • Medical Corporation Chiyukai Fukuoka Shin Mizumaki Hospital ( Site 1710)
    • Yukuhashi, Fukuoka, Japan, 824-0026
      • Shin Yukuhashi Hospital ( Site 1722)
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 720-8520
      • National Hospital Organization Fukuyama Medical Center ( Site 1706)
    • Fukuyama, Hiroshima, Japan, 721-8511
      • Fukuyama City Hospital ( Site 1721)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 062-0931
      • KKR Sapporo Medical Center ( Site 1728)
  • Hyogo
    • Kobe, Hyogo, Japan, 655-0031
      • Sano Hospital ( Site 1701)
  • Ibaraki
    • Higashiibaraki-gun, Ibaraki, Japan, 311-3193
      • National Hospital Organization Mito Medical Center ( Site 1729)
    • Koga, Ibaraki, Japan, 306-0041
      • Medical Corporation Tokushukai Koga General Hospital ( Site 1712)
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8530
      • Ishikawa Prefectural Central Hospital ( Site 1707)
    • Kanazawa, Ishikawa, Japan, 920-8650
      • National Hospital Organization Kanazawa Medical Center ( Site 1716)
  • Kagoshima
    • Aira, Kagoshima, Japan, 899-5431
      • Kawahara Clinic ( Site 1719)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 245-8575
      • National Hospital Organization Yokohama Medical Center ( Site 1702)
  • Mie
    • Tsu, Mie, Japan, 514-1101
      • National Hospital Organization Mie Chuo Medical Center ( Site 1727)
  • Miyagi
    • Sendai, Miyagi, Japan, 981-8563
      • Japan Labour Health And Safety Organization Tohoku Rosai Hospital ( Site 1714)
    • Sendai, Miyagi, Japan, 983-8520
      • National Hospital Organization Sendai Medical Center ( Site 1723)
  • Nagano
    • Suwa, Nagano, Japan, 392-8510
      • Suwa Red Cross Hospital ( Site 1705)
  • Nagasaki
    • Omura, Nagasaki, Japan, 856-8562
      • National Hospital Organization Nagasaki Medical Center ( Site 1718)
  • Osaka
    • Kawachinagano, Osaka, Japan, 586-8521
      • National Hospital Organization Osaka Minami Medical Center ( Site 1715)
  • Tochigi
    • Utsunomiya, Tochigi, Japan, 329-1193
      • National Hospital Organization Utsunomiya National Hospital ( Site 1711)
  • Wakayama
    • Tanabe, Wakayama, Japan, 646-8558
      • National Hospital Organization Minami Wakayama Medical Center ( Site 1725)
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-8506
      • Yamanashi Prefectural Central Hospital ( Site 1703)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• requires hospitalization and treatment with IV antibiotic therapy for complicated intraabdominal infection (cIAI) or complicated urinary tract infection (cUTI). Per-protocol diagnostic criteria apply to the qualifying infection types.
• infection is known or thought to be caused by microorganisms susceptible to the IV study therapy
• baseline specimen for primary infection site culture obtained at operative procedure in Screening period or at Baseline for cIAI participants, and within 48 hours before initiation of IV study drug for cUTI participants
• female or male who is not of reproductive potential, or female or male who is of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner from the time of consent through completion of the study, by practicing abstinence from heterosexual activity or using acceptable contraception during heterosexual activity.

Exclusion Criteria:

• received any amount of effective antibiotic therapy after obtaining the culture for admission to the study and before administration of the first dose of IV study therapy
• received treatment with systemic effective antibiotics for >24 hours within the 72 hours before initiation of study therapy
• has a concurrent infection, including endocarditis, osteomyelitis, meningitis, or prosthetic joint infection, that would interfere with evaluation of response to IMI/REL
• has a cIAI or cUTI due to a confirmed fungal pathogen
• has a cUTI that meets any of the following: 1) complete obstruction of any portion of the urinary tract, 2) known ileal loop, 3) intractable vesico-ureteral reflux, 4) presence of indwelling urinary catheter which cannot be removed at study entry
• has a cIAI that meets any of the following: 1) infection that should be managed by Staged Abdominal Repair (STAR) or open abdomen therapy, 2) infection limited to the hollow viscus
• history of serious allergy, hypersensitivity, or any serious reaction to any carbapenem, cephalosporin, penicillin or other beta-lactam agent, or other beta-lactamase inhibitors
• female who is pregnant or is expecting to conceive, is breastfeeding, or plans to breastfeed before completion of the study
• history of a seizure disorder
• anticipates to be treated with valproic acid, concomitant IV or an oral antimicrobial considered effective to the index pathogen, in addition to the study treatment
• is receiving immunosuppressive therapy, including high-dose corticosteroids
• is undergoing hemodialysis or peritoneal dialysis
• participated in any other clinical study involving an investigational or experimental medication during the previous 30 days before Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Imipenem+Cilastatin/Relebactam; Participants with cIAI or cUTI will receive imipenem+cilastatin/relebactam intravenous (IV) infusion once every 6 hours for 5 to 14 days	Drug: Imipenem+Cilastatin/Relebactam; Imipenem+Cilastatin/Relebactam 200/100 mg to 500/250 mg, depending on renal function, 30-minute IV infusion once every 6 hours; Other Names: MK-7655A; IMI/REL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing ≥1 Adverse Events (AE)	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.	Up to 28 days
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	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.	Up to 14 days (End of Therapy Visit)
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at End of Therapy Visit	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.	Between Day 5 and Day 14 (End of Therapy Visit)
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at End of Therapy Visit	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.	Between Day 5 and Day 14 (End of Therapy Visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at 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.	Between Day 10 and Day 23 (Test of Cure Visit)
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at 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.	Between Day 10 and Day 23 (Test of Cure Visit)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Kohno S, Bando H, Yoneyama F, Kikukawa H, Kawahara K, Shirakawa M, Aoyama N, Brown M, Paschke A, Takase A. The safety and efficacy of relebactam/imipenem/cilastatin in Japanese patients with complicated intra-abdominal infection or complicated urinary tract infection: A multicenter, open-label, noncomparative phase 3 study. J Infect Chemother. 2021 Feb;27(2):262-270. doi: 10.1016/j.jiac.2020.09.032. Epub 2020 Nov 13.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 4, 2017
• Primary Completion (ACTUAL): September 14, 2018
• Study Completion (ACTUAL): September 14, 2018

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (ACTUAL): September 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Infections; Communicable Diseases; Intraabdominal Infections; Urinary Tract Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protease Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Imipenem; Relebactam; Cilastatin; Cilastatin, Imipenem Drug Combination
• Other Study ID Numbers: 7655A-017; 173738 (REGISTRY: JAPIC-CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes