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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Intra-abdominal Infections

Treatments: Drug: Relebactam 125 mg; Drug: Relebactam 250 mg; Drug: Matching placebo to relebactam; Drug: Imipenem/cilastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01506271

2011-005686-20 (EudraCT Number)

7655-004

MK-7655-004 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 351 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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351 participants in 3 patient groups, including a placebo group

Relebactam 250 mg with imipenem/cilastatin

Experimental group

Description:

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.

Treatment:

Drug: Imipenem/cilastatin

Drug: Relebactam 250 mg

Relebactam 125 mg with imipenem/cilastatin

Experimental group

Description:

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.

Treatment:

Drug: Imipenem/cilastatin

Drug: Relebactam 125 mg

Placebo to relebactam with imipenem/cilastatin

Placebo Comparator group

Description:

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.

Treatment:

Drug: Imipenem/cilastatin

Drug: Matching placebo to relebactam