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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)

Primary Purpose

Complicated Intra-abdominal Infection, Complicated Urinary Tract Infection

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Imipenem+Cilastatin/Relebactam
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Complicated Intra-abdominal Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Nagoya Ekisaikai Hospital ( Site 1724)
  • Toyota Memorial Hospital ( Site 1708)
  • Medical Corporation Chiyukai Fukuoka Shin Mizumaki Hospital ( Site 1710)
  • Shin Yukuhashi Hospital ( Site 1722)
  • National Hospital Organization Fukuyama Medical Center ( Site 1706)
  • Fukuyama City Hospital ( Site 1721)
  • KKR Sapporo Medical Center ( Site 1728)
  • Sano Hospital ( Site 1701)
  • National Hospital Organization Mito Medical Center ( Site 1729)
  • Medical Corporation Tokushukai Koga General Hospital ( Site 1712)
  • Ishikawa Prefectural Central Hospital ( Site 1707)
  • National Hospital Organization Kanazawa Medical Center ( Site 1716)
  • Kawahara Clinic ( Site 1719)
  • National Hospital Organization Yokohama Medical Center ( Site 1702)
  • National Hospital Organization Mie Chuo Medical Center ( Site 1727)
  • Japan Labour Health And Safety Organization Tohoku Rosai Hospital ( Site 1714)
  • National Hospital Organization Sendai Medical Center ( Site 1723)
  • Suwa Red Cross Hospital ( Site 1705)
  • National Hospital Organization Nagasaki Medical Center ( Site 1718)
  • National Hospital Organization Osaka Minami Medical Center ( Site 1715)
  • National Hospital Organization Utsunomiya National Hospital ( Site 1711)
  • National Hospital Organization Minami Wakayama Medical Center ( Site 1725)
  • Yamanashi Prefectural Central Hospital ( Site 1703)
  • Fukuiken Saiseikai Hospital ( Site 1704)
  • Medical Corporation Chiyukai Fukuoka Wajiro Hospital ( Site 1709)
  • Medical Corporation Shingenkai Kawahara Urological Clinic ( Site 1726)
  • Medical Corporation Seifukai Yagi Clinic ( Site 1720)
  • National Hospital Organization Kumamoto Medical Center ( Site 1713)
  • National Hospital Organization Oita Medical Center ( Site 1717)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Imipenem+Cilastatin/Relebactam

Arm Description

Participants with cIAI or cUTI will receive imipenem+cilastatin/relebactam intravenous (IV) infusion once every 6 hours for 5 to 14 days

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
September 15, 2017
Last Updated
January 20, 2021
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03293485
Brief Title
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)
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
October 4, 2017 (Actual)
Primary Completion Date
September 14, 2018 (Actual)
Study Completion Date
September 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complicated Intra-abdominal Infection, Complicated Urinary Tract Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
83 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Imipenem+Cilastatin/Relebactam
Arm Type
Experimental
Arm Description
Participants with cIAI or cUTI will receive imipenem+cilastatin/relebactam intravenous (IV) infusion once every 6 hours for 5 to 14 days
Intervention Type
Drug
Intervention Name(s)
Imipenem+Cilastatin/Relebactam
Other Intervention Name(s)
IMI/REL, MK-7655A
Intervention Description
Imipenem+Cilastatin/Relebactam 200/100 mg to 500/250 mg, depending on renal function, 30-minute IV infusion once every 6 hours
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing ≥1 Adverse Events (AE)
Description
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.
Time Frame
Up to 28 days
Title
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
Description
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.
Time Frame
Up to 14 days (End of Therapy Visit)
Title
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at End of Therapy Visit
Description
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.
Time Frame
Between Day 5 and Day 14 (End of Therapy Visit)
Title
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at End of Therapy Visit
Description
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.
Time Frame
Between Day 5 and Day 14 (End of Therapy Visit)
Secondary Outcome Measure Information:
Title
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at Test of Cure Visit
Description
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.
Time Frame
Between Day 10 and Day 23 (Test of Cure Visit)
Title
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at Test of Cure Visit
Description
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.
Time Frame
Between Day 10 and Day 23 (Test of Cure Visit)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Nagoya Ekisaikai Hospital ( Site 1724)
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
454-8502
Country
Japan
Facility Name
Toyota Memorial Hospital ( Site 1708)
City
Toyota
State/Province
Aichi
ZIP/Postal Code
471-8513
Country
Japan
Facility Name
Medical Corporation Chiyukai Fukuoka Shin Mizumaki Hospital ( Site 1710)
City
Onga-gun
State/Province
Fukuoka
ZIP/Postal Code
807-0051
Country
Japan
Facility Name
Shin Yukuhashi Hospital ( Site 1722)
City
Yukuhashi
State/Province
Fukuoka
ZIP/Postal Code
824-0026
Country
Japan
Facility Name
National Hospital Organization Fukuyama Medical Center ( Site 1706)
City
Fukuyama
State/Province
Hiroshima
ZIP/Postal Code
720-8520
Country
Japan
Facility Name
Fukuyama City Hospital ( Site 1721)
City
Fukuyama
State/Province
Hiroshima
ZIP/Postal Code
721-8511
Country
Japan
Facility Name
KKR Sapporo Medical Center ( Site 1728)
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
062-0931
Country
Japan
Facility Name
Sano Hospital ( Site 1701)
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
655-0031
Country
Japan
Facility Name
National Hospital Organization Mito Medical Center ( Site 1729)
City
Higashiibaraki-gun
State/Province
Ibaraki
ZIP/Postal Code
311-3193
Country
Japan
Facility Name
Medical Corporation Tokushukai Koga General Hospital ( Site 1712)
City
Koga
State/Province
Ibaraki
ZIP/Postal Code
306-0041
Country
Japan
Facility Name
Ishikawa Prefectural Central Hospital ( Site 1707)
City
Kanazawa
State/Province
Ishikawa
ZIP/Postal Code
920-8530
Country
Japan
Facility Name
National Hospital Organization Kanazawa Medical Center ( Site 1716)
City
Kanazawa
State/Province
Ishikawa
ZIP/Postal Code
920-8650
Country
Japan
Facility Name
Kawahara Clinic ( Site 1719)
City
Aira
State/Province
Kagoshima
ZIP/Postal Code
899-5431
Country
Japan
Facility Name
National Hospital Organization Yokohama Medical Center ( Site 1702)
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
245-8575
Country
Japan
Facility Name
National Hospital Organization Mie Chuo Medical Center ( Site 1727)
City
Tsu
State/Province
Mie
ZIP/Postal Code
514-1101
Country
Japan
Facility Name
Japan Labour Health And Safety Organization Tohoku Rosai Hospital ( Site 1714)
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
981-8563
Country
Japan
Facility Name
National Hospital Organization Sendai Medical Center ( Site 1723)
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
983-8520
Country
Japan
Facility Name
Suwa Red Cross Hospital ( Site 1705)
City
Suwa
State/Province
Nagano
ZIP/Postal Code
392-8510
Country
Japan
Facility Name
National Hospital Organization Nagasaki Medical Center ( Site 1718)
City
Omura
State/Province
Nagasaki
ZIP/Postal Code
856-8562
Country
Japan
Facility Name
National Hospital Organization Osaka Minami Medical Center ( Site 1715)
City
Kawachinagano
State/Province
Osaka
ZIP/Postal Code
586-8521
Country
Japan
Facility Name
National Hospital Organization Utsunomiya National Hospital ( Site 1711)
City
Utsunomiya
State/Province
Tochigi
ZIP/Postal Code
329-1193
Country
Japan
Facility Name
National Hospital Organization Minami Wakayama Medical Center ( Site 1725)
City
Tanabe
State/Province
Wakayama
ZIP/Postal Code
646-8558
Country
Japan
Facility Name
Yamanashi Prefectural Central Hospital ( Site 1703)
City
Kofu
State/Province
Yamanashi
ZIP/Postal Code
400-8506
Country
Japan
Facility Name
Fukuiken Saiseikai Hospital ( Site 1704)
City
Fukui
ZIP/Postal Code
918-8503
Country
Japan
Facility Name
Medical Corporation Chiyukai Fukuoka Wajiro Hospital ( Site 1709)
City
Fukuoka
ZIP/Postal Code
811-0213
Country
Japan
Facility Name
Medical Corporation Shingenkai Kawahara Urological Clinic ( Site 1726)
City
Kagoshima
ZIP/Postal Code
890-0073
Country
Japan
Facility Name
Medical Corporation Seifukai Yagi Clinic ( Site 1720)
City
Kagoshima
ZIP/Postal Code
891-0105
Country
Japan
Facility Name
National Hospital Organization Kumamoto Medical Center ( Site 1713)
City
Kumamoto
ZIP/Postal Code
860-0008
Country
Japan
Facility Name
National Hospital Organization Oita Medical Center ( Site 1717)
City
Oita
ZIP/Postal Code
870-0263
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
33191112
Citation
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.
Results Reference
result

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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)

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