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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)

Phase 3
Completed
Conditions
Complicated Intra-abdominal Infection
Complicated Urinary Tract Infection
Interventions
Drug: Imipenem+Cilastatin/Relebactam
Registration Number
NCT03293485
Lead Sponsor
Merck Sharp & Dohme LLC
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
83
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Imipenem+Cilastatin/RelebactamImipenem+Cilastatin/RelebactamParticipants with cIAI or cUTI will receive imipenem+cilastatin/relebactam intravenous (IV) infusion once every 6 hours for 5 to 14 days
Primary Outcome Measures
NameTimeMethod
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at End of Therapy VisitBetween Day 5 and Day 14 (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.

Percentage of Participants Experiencing ≥1 Adverse Events (AE)Up to 28 days

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.

Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at End of Therapy VisitBetween Day 5 and Day 14 (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.

Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)Up to 14 days (End of Therapy Visit)

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at Test of Cure VisitBetween 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.

Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at Test of Cure VisitBetween 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.

Trial Locations

Locations (29)

Nagoya Ekisaikai Hospital ( Site 1724)

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Nagoya, Aichi, Japan

Toyota Memorial Hospital ( Site 1708)

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Toyota, Aichi, Japan

Medical Corporation Chiyukai Fukuoka Shin Mizumaki Hospital ( Site 1710)

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Onga-gun, Fukuoka, Japan

Shin Yukuhashi Hospital ( Site 1722)

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Yukuhashi, Fukuoka, Japan

National Hospital Organization Fukuyama Medical Center ( Site 1706)

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Fukuyama, Hiroshima, Japan

Ishikawa Prefectural Central Hospital ( Site 1707)

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Kanazawa, Ishikawa, Japan

Fukuyama City Hospital ( Site 1721)

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Fukuyama, Hiroshima, Japan

KKR Sapporo Medical Center ( Site 1728)

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Sapporo, Hokkaido, Japan

Sano Hospital ( Site 1701)

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Kobe, Hyogo, Japan

National Hospital Organization Mito Medical Center ( Site 1729)

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Higashiibaraki-gun, Ibaraki, Japan

Medical Corporation Tokushukai Koga General Hospital ( Site 1712)

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Koga, Ibaraki, Japan

National Hospital Organization Kanazawa Medical Center ( Site 1716)

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Kanazawa, Ishikawa, Japan

National Hospital Organization Sendai Medical Center ( Site 1723)

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Sendai, Miyagi, Japan

Yamanashi Prefectural Central Hospital ( Site 1703)

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Kofu, Yamanashi, Japan

National Hospital Organization Utsunomiya National Hospital ( Site 1711)

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Utsunomiya, Tochigi, Japan

Medical Corporation Chiyukai Fukuoka Wajiro Hospital ( Site 1709)

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Fukuoka, Japan

Medical Corporation Shingenkai Kawahara Urological Clinic ( Site 1726)

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Kagoshima, Japan

Medical Corporation Seifukai Yagi Clinic ( Site 1720)

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Kagoshima, Japan

Kawahara Clinic ( Site 1719)

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Aira, Kagoshima, Japan

National Hospital Organization Yokohama Medical Center ( Site 1702)

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Yokohama, Kanagawa, Japan

National Hospital Organization Mie Chuo Medical Center ( Site 1727)

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Tsu, Mie, Japan

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

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Sendai, Miyagi, Japan

National Hospital Organization Nagasaki Medical Center ( Site 1718)

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Omura, Nagasaki, Japan

Suwa Red Cross Hospital ( Site 1705)

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Suwa, Nagano, Japan

National Hospital Organization Osaka Minami Medical Center ( Site 1715)

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Kawachinagano, Osaka, Japan

National Hospital Organization Minami Wakayama Medical Center ( Site 1725)

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Tanabe, Wakayama, Japan

Fukuiken Saiseikai Hospital ( Site 1704)

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Fukui, Japan

National Hospital Organization Kumamoto Medical Center ( Site 1713)

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Kumamoto, Japan

National Hospital Organization Oita Medical Center ( Site 1717)

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Oita, Japan

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