Study of CB-183,315 in Participants With Clostridium Difficile Associated Diarrhea (MK-4261-005)

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: Surotomycin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01597505

2012-000252-34 (EudraCT Number)

MK-4261-005 (Other Identifier)

4261-005

LCD-CDAD-10-07 (Other Identifier)

Details and patient eligibility

About

606 participants with Clostridium Difficile Associated Diarrhea (CDAD) participated in this study and received either oral vancomycin or CB-183,315 (surotomycin) in a blinded fashion. Treatment lasted for 10 days and participants were followed up for at least 40 days and a maximum of 100 days. The purpose of this study was to evaluate how well surotomycin treats CDAD as compared to vancomycin.

Enrollment: 606 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

To be included in this study, participants must:

• Sign a consent form;
• Be >= 18 and < 90 years of age;
• Have diarrhea, at least 3 times during one day, or 200 mL or liquid stool if using a rectal device;
• Test positive for Clostridium difficile;
• If female, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study.

Participants will not be allowed into the study if they:

• Have toxic megacolon and/or known small bowel ileus;
• Have received treatment with intravenous immune globulin (IVIG) within the past 30 days;
• Have 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;
• Have received a certain amount of antibacterial therapy specific for current CDAD, unless it is not working;
• Have received an investigational vaccine against C. difficile;
• Have received an investigational product containing monoclonal antibodies against toxin A or B within 180 days;
• Had more than 2 episodes of CDAD within 90 days;
• Had major gastrointestinal (GI) surgery (i.e. significant bowel resection) within 3 months (this does not include appendectomy or cholecystectomy);
• Have history of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis;
• Are unable to discontinue loperamide, diphenoxylate/atropine, or cholestyramine during the duration of the study;
• Are 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;
• Had stool studies positive for pathogenic ova and/or parasites;
• Have an intolerance or hypersensitivity to daptomycin and/or vancomycin;
• Have life-threatening illness at the time of enrollment;
• Have poor concurrent medical risks that in the opinion of the Investigator the participant should not enroll;
• Have received an investigational drug or participated in any experimental procedure within 1 month;
• Have human immunodeficiency virus (HIV), a cluster of differentiation 4 (CD4) < 200 cells/mm3 within 6 months of start of study therapy;
• Anticipate that certain antibacterial therapy for a non-CDAD infection will be required for > 7 days;
• Are unable to discontinue Saccharomyces or similar probiotic;
• Are on a concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy;
• Are unable to comply with the protocol requirements;
• Have any condition that, in the opinion of the Investigator, might interfere;
• Are not expected to live for less than 8 weeks.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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606 participants in 2 patient groups

Surotomycin

Experimental group

Description:

250 mg Surotomycin over- encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg; and Placebo over encapsulated tablet administered orally, twice daily for 10 days

Treatment:

Drug: Surotomycin

Drug: Placebo

Vancomycin

Active Comparator group

Description:

125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days

Treatment:

Drug: Vancomycin