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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01506271
First received: January 5, 2012
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to determine whether adding 125 mg or 250 mg doses of MK-7655 to imipenem/cilastatin is at least as effective as imipenem/cilastatin alone in adults 18 years or older with Complicated Intra-Abdominal Infection (cIAI).


Condition Intervention Phase
Intra-abdominal Infections
Drug: MK-7655 250 mg with imipenem/cilastatin
Drug: MK-7655 125 mg with imipenem/cilastatin
Drug: imipenem/cilastatin with placebo
Drug: Matching placebo to MK-7655
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of MK-7655 + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone in Patients With Complicated Intra-Abdominal Infection [cIAI]

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Proportion of patients with a favorable clinical response at completion of IV study therapy [ Time Frame: 4 to 14 days post initiation of intravenous (IV) study therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with a favorable clinical response at completion of IV study therapy in patients who have imipenem-resistant, gram-negative cIAI infections. [ Time Frame: 4 to 14 days post initiation of intravenous (IV) study therapy. ] [ Designated as safety issue: No ]

Estimated Enrollment: 351
Study Start Date: June 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-7655 250 mg with imipenem/cilastatin Drug: MK-7655 250 mg with imipenem/cilastatin

Participants randomized to receive MK-7655 250 mg will be administered 250 mg doses of MK-7655 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.

Experimental: MK-7655 125 mg with imipenem/cilastatin Drug: MK-7655 125 mg with imipenem/cilastatin

Participants randomized to receive MK-7655 125 mg will be administered 125 mg doses of MK-7655 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.

Active Comparator: imipenem / cilastatin with placebo Drug: imipenem/cilastatin with placebo
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.
Drug: Matching placebo to MK-7655
Participants randomized to receive imipenem/cilastatin alone will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01506271

  Show 23 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01506271     History of Changes
Other Study ID Numbers: 7655-004
Study First Received: January 5, 2012
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Complicated Intra-abdominal Infections

Additional relevant MeSH terms:
Intraabdominal Infections
Infection
Cilastatin
Imipenem
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014