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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01506271
First received: January 5, 2012
Last updated: October 6, 2014
Last verified: October 2014
  Purpose

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


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:
  • Percentage of participants with a favorable clinical response at completion of IV study therapy [ Time Frame: 4 to 14 days post initiation of intravenous (IV) study therapy (up to postrandomization day 14) ] [ Designated as safety issue: No ]
  • Percentage of participants with an elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) laboratory values that are greater than or equal to 5X the upper limit of normal (ULN) [ Time Frame: Up to 14 days following completion of all study therapy ] [ Designated as safety issue: Yes ]
  • Percentage of participants with elevated AST or ALT laboratory values that are greater than or equal to 3X the ULN, as well as elevated total bilirubin greater than or equal to 2X the ULN, and alkaline phosphatase values that are less than 2X the ULN [ Time Frame: Up to 14 days following completion of all study therapy ] [ Designated as safety issue: Yes ]
  • Percentage of participants with any adverse event (AE) [ Time Frame: Up to 14 days following completion of all study therapy ] [ Designated as safety issue: Yes ]
  • Percentage of participants with any serious adverse event (SAE) [ Time Frame: Up to 42 days following completion of all study therapy ] [ Designated as safety issue: Yes ]
  • Percentage of participants with any drug-related AE [ Time Frame: Up to 14 days following completion of all study therapy ] [ Designated as safety issue: Yes ]
  • Percentage of participants with any SAE and drug-related AE [ Time Frame: Up to 42 days following completion of all study therapy ] [ Designated as safety issue: Yes ]
  • Percentage of participants who discontinued IV study therapy due to an AE [ Time Frame: Up to 14 days post initiation of IV study therapy ] [ Designated as safety issue: Yes ]
  • Percentage of participants who discontinued IV study therapy due to a drug-related AE [ Time Frame: Up to 14 days post initiation of IV study therapy ] [ Designated as safety issue: Yes ]
  • Percentage of participants with specific AEs, system organ class (SOC) or pre-defined limit of change (PDLC) with incidence of >= 4 participants in one treatment group [ Time Frame: Up to 14 days following completion of all study therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of participants with a favorable clinical response at completion of IV study therapy in participants who have imipenem-resistant, gram-negative cIAI infections. [ Time Frame: 4 to 14 days post initiation of IV study therapy (up to postrandomization day 14). ] [ Designated as safety issue: No ]
  • Percentage of participants with a favorable clinical response at early follow-up [ Time Frame: Up to 9 days following completion of all study therapy ] [ Designated as safety issue: No ]
  • Percentage of participants with a favorable microbiological response at completion of IV study therapy [ Time Frame: Up to 14 days post initiation of IV study therapy (up to postrandomization day 14) ] [ Designated as safety issue: No ]
  • Percentage of participants with a favorable microbiological response at early follow-up [ Time Frame: Up to 9 days following completion of all study therapy ] [ Designated as safety issue: No ]
  • Percentage of participants with a favorable clinical response at late follow-up [ Time Frame: Up to 42 days following completion of all study therapy ] [ Designated as safety issue: No ]
  • Percentage of participants with a favorable microbiological response at late follow-up [ Time Frame: Up to 42 days following completion of all study therapy ] [ Designated as safety issue: No ]

Enrollment: 351
Study Start Date: June 2012
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-7655 250 mg with imipenem/cilastatin
MK-7655 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
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
MK-7655 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
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.

Placebo Comparator: Placebo to MK-7655 with imipenem/cilastatin
Matching placebo to MK-7655 (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
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

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director 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, 2011-005686-20
Study First Received: January 5, 2012
Last Updated: October 6, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 29, 2014