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)

Complicated Urinary Tract Infection Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03293485
• Other study ID #: 7655A-017
• Secondary ID: 173738
• Status: Completed
• Phase: Phase 3
• Start date: October 4, 2017
• Est. completion date: September 14, 2018

Study information

• Verified date: January 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: September 14, 2018
• Est. primary completion date: September 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Complicated Intra-abdominal Infection
• Complicated Urinary Tract Infection
• Infection
• Intraabdominal Infections
• Urinary Tract Infections

Intervention

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

Locations

Country	Name	City	State
Japan	Kawahara Clinic ( Site 1719)	Aira	Kagoshima
Japan	Fukuiken Saiseikai Hospital ( Site 1704)	Fukui
Japan	Medical Corporation Chiyukai Fukuoka Wajiro Hospital ( Site 1709)	Fukuoka
Japan	Fukuyama City Hospital ( Site 1721)	Fukuyama	Hiroshima
Japan	National Hospital Organization Fukuyama Medical Center ( Site 1706)	Fukuyama	Hiroshima
Japan	National Hospital Organization Mito Medical Center ( Site 1729)	Higashiibaraki-gun	Ibaraki
Japan	Medical Corporation Seifukai Yagi Clinic ( Site 1720)	Kagoshima
Japan	Medical Corporation Shingenkai Kawahara Urological Clinic ( Site 1726)	Kagoshima
Japan	Ishikawa Prefectural Central Hospital ( Site 1707)	Kanazawa	Ishikawa
Japan	National Hospital Organization Kanazawa Medical Center ( Site 1716)	Kanazawa	Ishikawa
Japan	National Hospital Organization Osaka Minami Medical Center ( Site 1715)	Kawachinagano	Osaka
Japan	Sano Hospital ( Site 1701)	Kobe	Hyogo
Japan	Yamanashi Prefectural Central Hospital ( Site 1703)	Kofu	Yamanashi
Japan	Medical Corporation Tokushukai Koga General Hospital ( Site 1712)	Koga	Ibaraki
Japan	National Hospital Organization Kumamoto Medical Center ( Site 1713)	Kumamoto
Japan	Nagoya Ekisaikai Hospital ( Site 1724)	Nagoya	Aichi
Japan	National Hospital Organization Oita Medical Center ( Site 1717)	Oita
Japan	National Hospital Organization Nagasaki Medical Center ( Site 1718)	Omura	Nagasaki
Japan	Medical Corporation Chiyukai Fukuoka Shin Mizumaki Hospital ( Site 1710)	Onga-gun	Fukuoka
Japan	KKR Sapporo Medical Center ( Site 1728)	Sapporo	Hokkaido
Japan	Japan Labour Health And Safety Organization Tohoku Rosai Hospital ( Site 1714)	Sendai	Miyagi
Japan	National Hospital Organization Sendai Medical Center ( Site 1723)	Sendai	Miyagi
Japan	Suwa Red Cross Hospital ( Site 1705)	Suwa	Nagano
Japan	National Hospital Organization Minami Wakayama Medical Center ( Site 1725)	Tanabe	Wakayama
Japan	Toyota Memorial Hospital ( Site 1708)	Toyota	Aichi
Japan	National Hospital Organization Mie Chuo Medical Center ( Site 1727)	Tsu	Mie
Japan	National Hospital Organization Utsunomiya National Hospital ( Site 1711)	Utsunomiya	Tochigi
Japan	National Hospital Organization Yokohama Medical Center ( Site 1702)	Yokohama	Kanagawa
Japan	Shin Yukuhashi Hospital ( Site 1722)	Yukuhashi	Fukuoka

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Japan, 

References & 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 tra — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)