Study of the Safety, Tolerability, and Efficacy of MK-7655 + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone for the Treatment of Complicated Urinary Tract Infection (cUTI) (MK-7655-003)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01505634
First received: January 4, 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 urinary tract infection (cUTI). The primary hypothesis is that the MK-7655 + imipenem/cilastatin treatment regimen is non-inferior to imipenem/cilastatin with respect to the proportion of participants with a favorable microbiological response at completion of intravenous (IV) study therapy.


Condition Intervention Phase
Urinary Tract Infections
Pyelonephritis
Drug: MK-7655 250 mg
Drug: MK-7655 125 mg
Drug: imipenem/cilastatin 500 mg
Drug: Placebo to MK-7655
Drug: Ciprofloxacin
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 Urinary Tract Infection (cUTI)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of participants with a favorable microbiological response at completion of IV study therapy [ Time Frame: At time of last IV dose of study drug (up to postrandomization day 14) ] [ Designated as safety issue: No ]
  • Percentage of participants with an elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) laboratory value that is 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 microbiological response at completion of IV study therapy who have imipenem-resistant, gram-negative cUTI infections. [ Time Frame: At time of last IV dose of study drug (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 IV and oral therapy ] [ Designated as safety issue: No ]
  • Percentage of participants with a favorable clinical response at completion of IV study therapy [ Time Frame: At time of last IV dose of study drug (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 IV and oral 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 IV and oral 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 IV and oral therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: May 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (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
Participants randomized to receive MK-7655 250 mg will be administered a 250 mg dose 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 IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.
Drug: imipenem/cilastatin 500 mg
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: Ciprofloxacin
After at least 96 hours of IV treatment, participants may be switched, at the discretion of the investigator, to 500 mg ciprofloxacin, administered orally, twice daily
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
Participants randomized to receive MK-7655 125 mg will be administered a 125 mg dose 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.
Drug: imipenem/cilastatin 500 mg
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: Ciprofloxacin
After at least 96 hours of IV treatment, participants may be switched, at the discretion of the investigator, to 500 mg ciprofloxacin, administered orally, twice daily
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 500 mg
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: 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.
Drug: Ciprofloxacin
After at least 96 hours of IV treatment, participants may be switched, at the discretion of the investigator, to 500 mg ciprofloxacin, administered orally, twice daily

  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 cUTI or acute

pyelonephritis judged by the investigator to be serious (requiring hospitalization and treatment with IV antibiotic therapy)

- Pyuria, determined by a midstream clean-catch (MSCC) or catheterized

(indwelling or straight catheter) urine specimen with greater than or equal to 10 white blood cells (WBCs) per high-power field (hpf) on standard examination of urine sediment or greater than or equal to 10 WBCs/mm3 in unspun urine

- One positive urine culture within 48 hours of enrollment

Exclusion Criteria:

- Complete obstruction of any portion of the urinary tract (requiring a

permanent indwelling urinary catheter or instrumentation), a known ileal loop, or intractable vesico-ureteral reflux

  • A temporary indwelling urinary catheter is in place and cannot be removed at study entry.
  • Perinephric or intrarenal abscess or known or suspected prostatitis
  • Uncomplicated UTI
  • Any history of recent accidental trauma to the pelvis or urinary tract
  • Any amount of effective antibiotic therapy after obtaining the urine 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 greater than 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 beta (β)-lactam agents

  • History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to other beta-lactam inhibitors (e.g., tazobactam, sulbactam, clavulanic acid)
  • History of a seizure disorder
  • Currently being treated with valproic acid or has received treatment with

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, breast feeding, or plans to breast feed

during the study

- A response to all study therapy (IV study therapy or subsequent oral

ciprofloxacin) 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 (use of vancomycin, daptomycin, or linezolid is allowed for certain infections)

  • cUTI due to a confirmed fungal pathogen
  • Currently receiving immunosuppressive therapy, including use of high-dose

corticosteroids

  • Prior recipient of a renal transplantation
  • Laboratory abnormalities as specified in protocol
  • 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

- 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 this trial

- Estimated or actual creatinine clearance of <5 mL/minute, or is currently undergoing hemodialysis

  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: NCT01505634

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 19 Study Locations
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: NCT01505634     History of Changes
Other Study ID Numbers: 7655-003, 2011-005707-32
Study First Received: January 4, 2012
Last Updated: October 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Tract Infections
Communicable Diseases
Infection
Pyelonephritis
Kidney Diseases
Nephritis
Nephritis, Interstitial
Pyelitis
Urologic Diseases
Cilastatin
Ciprofloxacin
Imipenem
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014