Study of CB-183,315 in Participants With Clostridium Difficile Infection

NCT ID: NCT01085591

Last Updated: 2018-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-01
• Study Completion Date: 2011-05-13

Brief Summary

This is a randomized, double-blind, single-placebo, active-controlled, dose ranging parallel group design with 3 arms. Two dose regimens of CB-183,315 dosed twice daily will be compared with the active comparator oral vancomycin (125 milligrams (mg ) four times daily). Participants with diarrhea at risk for Clostridium difficile infection (CDI) [for example, received prior or concomitant antibiotic(s)] will be identified and tested for C. difficile toxin in stool using an enzyme immunoassay (EIA), or polymerase chain reaction (PCR) per the usual standard of care. Eligible participants will be consented, undergo baseline evaluations, and will be randomized in a blinded fashion to one of 3 treatment arms.

Participants will be randomized to receive either 125 mg CB-183,315 twice daily alternating with placebo tablets twice daily, 250 mg CB-183,315 twice daily alternating with placebo tablets twice daily or 125 mg oral vancomycin four times dailyover a period of 10 days in a 1:1:1 fashion.

Conditions

Clostridium Difficile Infection; Diarrhea

Study Design

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

Study Groups

CB-183,315, 125 mg

125 milligrams (mg) CB 183,315 administered orally twice daily, alternating with twice daily oral administration of placebo tablets, for 10 days.

Group Type: EXPERIMENTAL

CB-183,315

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

CB-183,315, 250 mg

250 mg CB 183,315 administered orally twice daily, alternating with twice daily oral administration of placebo tablets, for 10 days.

Group Type: EXPERIMENTAL

CB-183,315

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Vancomycin, 125 mg

125 mg vancomycin administered orally four times a day for 10 days.

Group Type: ACTIVE_COMPARATOR

Vancomycin

Intervention Type: DRUG

Interventions

CB-183,315

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Vancomycin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Informed Consent obtained and signed
• Age ≥ 18 years
• If female, participant is non-lactating, and is either:

• Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy
• Of childbearing potential and is practicing the barrier method of birth control along with one of the following methods: oral or parenteral contraceptives for 3 months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse
• Established non-severe or severe CDI (after Data Monitoring Committee [DMC] review) with a positive stool test for toxin A and/or B within 72 hours prior to first dose of study drug.

Exclusion Criteria

A participant will not be enrolled if s/he meets any of the following criteria:

• Female and pregnant or lactating
• Toxic megacolon and/or known small bowel ileus
• Received treatment with intravenous (IV) immune globulin within 30 days prior to the first dose of study drug
• Antibacterial therapy specific for current CDI or that may be effective for CDI even if given for a different indication:

• Received more than 24 hours of oral vancomycin for the current episode of CDI prior to first dose of study drug.
• Received more than 24 hours of oral/intravenous metronidazole OR any other therapy specific for the current episode of CDI immediately prior to first dose of study drug unless the participant received at least 3 days of such therapy, and is considered a treatment failure for CDI.
• Received more than 24 hours of oral/intravenous metronidazole for any other indication in the 3 days prior to first dose of study drug.
• Participants with more than 2 episodes of CDI within 90 days (that is, participants can be enrolled with their 1st recurrence/2nd episode)
• Major gastrointestinal (GI) surgery (that is, significant bowel resection including total colectomy with ileostomy) within 3 months of enrollment (this does not include appendectomy or cholecystectomy)
• History of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis
• Unable to stop loperamide, diphenoxylate, and cholestyramine during the duration of the study
• Unable to stop opiate treatment, unless on a stable dose as of onset of diarrhea and no change in dose planned for the duration of the study
• Known positive stool cultures for other enteropathogens, including but not limited to Salmonella, Shigella and Campylobacter
• Known stool studies positive for ova and/or parasites
• Known intolerance or hypersensitivity to daptomycin and/or vancomycin
• Poor concurrent medical risks with clinically significant co-morbid disease such that in the opinion of the Investigator the participant should not be enrolled
• Received an investigational drug or participated in any experimental procedure within 1 month prior to study entry
• Previously enrolled in this study
• Received an investigational vaccine against C. difficile
• Participants with known Hepatitis B or Hepatitis C who have alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal (ULN) and/or bilirubin > 1.5 times the ULN
• Human immunodeficiency virus positive, unless controlled (that is, on triple therapy) and with a CD4 > 200 cells per millimeter cubed (cellsmm˄3)
• Anticipated that systemic antibacterial therapy for a non-CDI infections will be required for >7 days after start of study therapy
• Concurrent therapy with daptomycin
• Unable to discontinue Saccharomyces or similar probiotic
• Known active IV drug or alcohol abuse
• Concurrent intensive chemotherapy, radiotherapy or biologic treatment for active malignancy (may only be enrolled after consultation with Medical Monitor)
• Unable to comply with the protocol requirements
• Any condition that, in the opinion of the Investigator, might interfere with study objectives
• Life expectancy is less than 6 weeks

Additional Exclusions for Participants with Severe CDI

In addition to the criteria listed above, a participant who meets the definition of severe CDI will not be enrolled if the participant meets any of the following criteria:

• Age > 80
• Hypotension, defined by sustained systolic blood pressure < 90 millimeters of mercury (mmHg), or need for vasopressors to maintain blood pressure
• Abdominal rebound tenderness on examination
• Acute kidney insufficiency defined by:

• oliguria (< 20 cubic centimeter [cc] urine output per hour over a 4 hour period not responsive to attempts to increase renal perfusion) or
• non-perfusion (for example, pre-renal) related azotemia with initial creatinine (Baseline) > 2.5 milligrams per deciliter (mg/dL) and blood urea nitrogen (BUN) > 40 mg/dL with no prior history of chronic kidney disease
• Unable to tolerate oral medications due to persistent vomiting 2. White blood cell (WBC) count > 30,000/mm˄3

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

Sponsors

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Providence Hospital Clinical Research Center

Washington D.C., District of Columbia, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

Central Florida Internists

Saint Cloud, Florida, United States

Atlanta Institute for Medical Research, Inc

Decatur, Georgia, United States

Gastrointestinal Specialists of Georgia PC

Marietta, Georgia, United States

Wellstar Infectious Disease

Marietta, Georgia, United States

Idaho Falls Infectious Disease, PLLC

Idaho City, Idaho, United States

University of Chicago

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Metropolitan Gastroentrology Group

Chevy Chase, Maryland, United States

Tufts University School of Medicine

Boston, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Keego Harbor, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Missouri Baptist Medical Center

St Louis, Missouri, United States

Mercury Street Medical Group - Research Group

Butte, Montana, United States

DiGiovanna Institute for Medical Education and Research

North Massapequa, New York, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

MeritCare Clinical Research

Fargo, North Dakota, United States

Remington Davis Inc.

Columbus, Ohio, United States

University of Calgary, Foothills Medical Center

Calgary, Alberta, Canada

St. Joseph Healthcare

Hamilton, Ontario, Canada

Queen's University

Kingston, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Centre de Sante et des Services Sociaux de Chicoutimi

Chicoutimi, Quebec, Canada

Maisonneuve Rosemont Hospital

Montreal, Quebec, Canada

SMBD- Jewish General Hospital G-139

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Québec

Québec, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke

Sherbrook, Quebec, Canada

Centre hopitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, Canada

Countries

United States; Canada

References

Lee CH, Patino H, Stevens C, Rege S, Chesnel L, Louie T, Mullane KM. Surotomycin versus vancomycin for Clostridium difficile infection: Phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial. J Antimicrob Chemother. 2016 Oct;71(10):2964-71. doi: 10.1093/jac/dkw246. Epub 2016 Jul 17.

Reference Type: RESULT

PMID: 27432604 (View on PubMed)

Other Identifiers

LCD-DR-09-03

Identifier Type: OTHER

Identifier Source: secondary_id

4261-007

Identifier Type: -

Identifier Source: org_study_id