Study of the Safety, Tolerability, and Efficacy of Relebactam (MK-7655) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone to Treat Complicated Intra-Abdominal Infection [cIAI] (MK-7655-004)

NCT ID: NCT01506271

Last Updated: 2019-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 351 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-01
• Study Completion Date: 2014-08-12

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125 mg or 250 mg doses of relebactam (MK-7655) to imipenem/cilastatin in adults 18 years or older with Complicated Intra-Abdominal Infection (cIAI). The primary hypothesis is that the relebactam + imipenem/cilastatin treatment regimen is non-inferior to treatment with imipenem/cilastatin alone with respect to the percentage of participants with a favorable clinical response at completion of intravenous (IV) study therapy.

Conditions

Intra-abdominal Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Relebactam 250 mg with imipenem/cilastatin

Participants randomized to receive relebactam 250 mg will be administered 250 mg doses of relebactam IV in a blinded fashion once every 6 hours with each dose infused over a 30-minute interval. A 500 mg dose of imipenem/cilastatin will be administered in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.

Group Type: EXPERIMENTAL

Relebactam 250 mg

Intervention Type: DRUG

Relebactam 250 mg IV every 6 hours for a minimum of 96 hours

Imipenem/cilastatin

Intervention Type: DRUG

A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.

Relebactam 125 mg with imipenem/cilastatin

Participants randomized to receive relebactam 125 mg will be administered 125 mg doses of relebactam IV, in a blinded-treatment fashion once every 6 hours with each dose infused over a 30-minute interval. A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.

Group Type: EXPERIMENTAL

Relebactam 125 mg

Intervention Type: DRUG

Relebactam 125 mg IV every 6 hours for a minimum of 96 hours

Imipenem/cilastatin

Intervention Type: DRUG

A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.

Placebo to relebactam with imipenem/cilastatin

Participants randomized to receive placebo for relebactam will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 hours. A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.

Group Type: PLACEBO_COMPARATOR

Imipenem/cilastatin

Intervention Type: DRUG

A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.

Matching placebo to relebactam

Intervention Type: DRUG

Placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.

Interventions

Relebactam 250 mg

Relebactam 250 mg IV every 6 hours for a minimum of 96 hours

Intervention Type: DRUG

Relebactam 125 mg

Relebactam 125 mg IV every 6 hours for a minimum of 96 hours

Intervention Type: DRUG

Imipenem/cilastatin

A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.

Intervention Type: DRUG

Matching placebo to relebactam

Placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.

Intervention Type: DRUG

Other Intervention Names

MK-7655; MK-7655

Eligibility Criteria

Inclusion Criteria

• Clinically suspected and/or bacteriologically documented cIAI requiring hospitalization and treatment with IV antibiotic therapy.
• Enrolled intraoperatively or postoperatively on the basis of operative findings OR enrolled preoperatively on the basis of compelling preoperative clinical findings.

Exclusion Criteria

• Infection which should be managed by Staged Abdominal Repair (STAR) or open abdomen technique.
• Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 30.
• Any amount of effective antibiotic therapy after obtaining the culture for admission to this study and prior to the administration of the first dose of IV study therapy.
• An infection which has been treated with >24 hours of systemic antibiotic therapy known to be effective against the presumed or documented etiologic pathogen(s) within the 72-hour period immediately prior to consideration for entry into the study.
• History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to carbapenem antibiotics, any cephalosporins, penicillins, or other β-lactam agents.
• History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to other β-lactamase inhibitors (e.g., tazobactam, sulbactam, clavulanic acid).
• History of a seizure disorder (requiring ongoing treatment with anticonvulsive therapy or prior treatment with anti-convulsive therapy in the last 3 years).
• Currently being treated with valproic acid or has used valproic acid in the 2 weeks prior to screening.
• Rapidly progressive or terminal illness (unlikely to survive the approximately 6- to 8-week study period).
• Pregnant or expecting to conceive, breastfeeding, or plans to breast feed within 1 month of completion of the study.
• Participant in whom a response to IV study therapy within the timeframe of treatment specified in this protocol is considered unlikely.
• Concurrent infection that would interfere with evaluation of response to the study antibiotics.
• Need for concomitant systemic antimicrobial agents in addition to those designated in the various study treatment groups.
• cIAI due to a confirmed fungal pathogen.
• Currently receiving immunosuppressive therapy, including use of high-dose corticosteroids.
• Prior recipient of a renal transplantation.
• Estimated or actual creatinine clearance of <50 mL/minute.
• History of any other illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drug to the patient.
• Laboratory abnormalities as specified in protocol.
• Currently participating in, or has participated in any other clinical study involving the administration of investigational or experimental medication (not licensed by regulatory agencies) at the time of presentation or during the previous 30 days prior to screening or is anticipated to participate in such a clinical study during the course of the trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Lucasti C, Vasile L, Sandesc D, Venskutonis D, McLeroth P, Lala M, Rizk ML, Brown ML, Losada MC, Pedley A, Kartsonis NA, Paschke A. Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6234-43. doi: 10.1128/AAC.00633-16. Print 2016 Oct.

Reference Type: RESULT

PMID: 27503659 (View on PubMed)

Other Identifiers

2011-005686-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-7655-004

Identifier Type: OTHER

Identifier Source: secondary_id

7655-004

Identifier Type: -

Identifier Source: org_study_id