A Study of CB-183,315 in Participants With Clostridium Difficile Associated Diarrhea (MK-4261-006)

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

Status and phase: Completed; Phase 3

Conditions: Clostridium Difficile Infection

Treatments: Drug: Vancomycin; Drug: Placebo; Drug: CB-183,315

Study type: Interventional

Funder types: Industry

Identifiers

NCT01598311

2012-000252-34 (EudraCT Number)

MK-4261-006 (Other Identifier)

4261-006

LCD-CDAD-11-06 (Other Identifier)

Details and patient eligibility

About

A total of 608 participants with Clostridium Difficile Associated Diarrhea (CDAD) will participate in this study; participants will receive either oral vancomycin or CB-183,315 in a blinded fashion. Treatment will last for 10 days and participants will be followed up for at least 40 days and a maximum of 100 days. The purpose of this study is to evaluate how well CB-183,315 treats CDAD as compared to vancomycin.

Enrollment: 608 patients

Sex: All

Ages: 18 to 89 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is able to read and sign a consent form;
• Is from ≥18 to <90 years of age;
• Has diarrhea, at least 3 times during one day, or 200 mL or liquid stool if using a rectal device;
• Tests positive for Clostridium difficile;
• If female, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study.

Exclusion criteria

• Has toxic megacolon and/or known small bowel ileus;
• Has received treatment with intravenous immune globulin (IVIG) within the past 30 days;
• Has received treatment with a fecal transplant within 7 days, and/or if the doctor anticipates to give the participant a fecal transplant during the study;
• Has received a certain amount of antibacterial therapy specific for current CDAD, unless it is not working;
• Has received an investigational vaccine against Clostridium difficile;
• Has received an investigational product containing monoclonal antibodies against toxin A or B within 180 days;
• Has more than 2 episodes of CDAD within 90 days;
• Has had major gastrointestinal (GI) surgery (i.e. significant bowel resection) within 3 months (this does not include appendectomy or cholecystectomy);
• Has a history of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis;
• Is unable to discontinue loperamide, diphenoxylate/atropine, or cholestyramine during the duration of the study;
• Is unable to discontinue opiate treatment unless on a stable dose;
• Has known positive stool cultures for other enteropathogens including but not limited to Salmonella, Shigella, and Campylobacter;
• Has had stool studies positive for pathogenic ova and/or parasites;
• Has an intolerance or hypersensitivity to daptomycin and/or vancomycin;
• Has a life-threatening illness at the time of enrollment;
• Has poor concurrent medical risks that in the opinion of the Investigator the participant should not enroll;
• Has received an investigational drug or participated in any experimental procedure within 1 month;
• Has human immunodeficiency virus (HIV), a cluster of differentiation (CD) 4 count <200 cells/mm^3 within 6 months of start of study therapy;
• Anticipates that certain antibacterial therapy for a non-CDAD infection will be required for >7 days;
• Is unable to discontinue Saccharomyces or similar probiotic;
• Is on a concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy;
• Is unable to comply with the protocol requirements;
• Has any condition that, in the opinion of the Investigator, might interfere;
• Is not expected to live for less than 8 weeks.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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608 participants in 2 patient groups

CB-183,315

Experimental group

Description:

Participants took CB-183,315 250 mg twice daily (b.i.d.) and placebo capsules b.i.d. by mouth for 10 days.

Treatment:

Drug: Placebo

Drug: CB-183,315

Vancomycin

Active Comparator group

Description:

Participants took vancomycin 125 mg four times daily (q.i.d.) by mouth for 10 days.

Treatment:

Drug: Vancomycin