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)

NCT03293485 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 7655A-017173738
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 29

Brief Summary

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).

Conditions

Complicated Intra-abdominal Infection; Complicated Urinary Tract Infection

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at Test of Cure Visit

  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

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

Study Arms (1)

Imipenem+Cilastatin/Relebactam

EXPERIMENTAL

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

Interventions

Imipenem+Cilastatin/Relebactam DRUG

Imipenem+Cilastatin/Relebactam 200/100 mg to 500/250 mg, depending on renal function, 30-minute IV infusion once every 6 hours

Also known as: IMI/REL, MK-7655A

Imipenem+Cilastatin/Relebactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (29)

Nagoya Ekisaikai Hospital ( Site 1724)

Nagoya, Aichi-ken, 454-8502, Japan

Location

Toyota Memorial Hospital ( Site 1708)

Toyota, Aichi-ken, 471-8513, Japan

Location

Medical Corporation Chiyukai Fukuoka Shin Mizumaki Hospital ( Site 1710)

Onga-gun, Fukuoka, 807-0051, Japan

Location

Shin Yukuhashi Hospital ( Site 1722)

Yukuhashi, Fukuoka, 824-0026, Japan

Location

National Hospital Organization Fukuyama Medical Center ( Site 1706)

Fukuyama, Hiroshima, 720-8520, Japan

Location

Fukuyama City Hospital ( Site 1721)

Fukuyama, Hiroshima, 721-8511, Japan

Location

KKR Sapporo Medical Center ( Site 1728)

Sapporo, Hokkaido, 062-0931, Japan

Location

Sano Hospital ( Site 1701)

Kobe, Hyōgo, 655-0031, Japan

Location

National Hospital Organization Mito Medical Center ( Site 1729)

Higashiibaraki-gun, Ibaraki, 311-3193, Japan

Location

Medical Corporation Tokushukai Koga General Hospital ( Site 1712)

Koga, Ibaraki, 306-0041, Japan

Location

Ishikawa Prefectural Central Hospital ( Site 1707)

Kanazawa, Ishikawa-ken, 920-8530, Japan

Location

National Hospital Organization Kanazawa Medical Center ( Site 1716)

Kanazawa, Ishikawa-ken, 920-8650, Japan

Location

Kawahara Clinic ( Site 1719)

Aira, Kagoshima-ken, 899-5431, Japan

Location

National Hospital Organization Yokohama Medical Center ( Site 1702)

Yokohama, Kanagawa, 245-8575, Japan

Location

National Hospital Organization Mie Chuo Medical Center ( Site 1727)

Tsu, Mie-ken, 514-1101, Japan

Location

Japan Labour Health And Safety Organization Tohoku Rosai Hospital ( Site 1714)

Sendai, Miyagi, 981-8563, Japan

Location

National Hospital Organization Sendai Medical Center ( Site 1723)

Sendai, Miyagi, 983-8520, Japan

Location

Suwa Red Cross Hospital ( Site 1705)

Suwa, Nagano, 392-8510, Japan

Location

National Hospital Organization Nagasaki Medical Center ( Site 1718)

Ōmura, Nagasaki, 856-8562, Japan

Location

National Hospital Organization Osaka Minami Medical Center ( Site 1715)

Kawachi-Nagano, Osaka, 586-8521, Japan

Location

National Hospital Organization Utsunomiya National Hospital ( Site 1711)

Utsunomiya, Tochigi, 329-1193, Japan

Location

National Hospital Organization Minami Wakayama Medical Center ( Site 1725)

Tanabe, Wakayama, 646-8558, Japan

Location

Yamanashi Prefectural Central Hospital ( Site 1703)

Kofu, Yamanashi, 400-8506, Japan

Location

Fukuiken Saiseikai Hospital ( Site 1704)

Fukui, 918-8503, Japan

Location

Medical Corporation Chiyukai Fukuoka Wajiro Hospital ( Site 1709)

Fukuoka, 811-0213, Japan

Location

Medical Corporation Shingenkai Kawahara Urological Clinic ( Site 1726)

Kagoshima, 890-0073, Japan

Location

Medical Corporation Seifukai Yagi Clinic ( Site 1720)

Kagoshima, 891-0105, Japan

Location

National Hospital Organization Kumamoto Medical Center ( Site 1713)

Kumamoto, 860-0008, Japan

Location

National Hospital Organization Oita Medical Center ( Site 1717)

Ōita, 870-0263, Japan

Location

Related Publications (1)

• 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.

  PMID: 33191112 RESULT

MeSH Terms

Interventions

imipenem, cilastatin and relebactam

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2017
• First Posted: September 26, 2017
• Study Start: October 4, 2017
• Primary Completion: September 14, 2018
• Study Completion: September 14, 2018
• Last Updated: February 12, 2021
• Results First Posted: September 17, 2019

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share

Locations

JP (29)