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

Phase 3

Completed

Conditions: Clostridium Difficile Infection

Interventions: Drug: CB-183,315
Drug: Vancomycin
Drug: Placebo

Registration Number: NCT01598311

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

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 608

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CB-183,315	Placebo	Participants took CB-183,315 250 mg twice daily (b.i.d.) and placebo capsules b.i.d. by mouth for 10 days.
CB-183,315	CB-183,315	Participants took CB-183,315 250 mg twice daily (b.i.d.) and placebo capsules b.i.d. by mouth for 10 days.
Vancomycin	Vancomycin	Participants took vancomycin 125 mg four times daily (q.i.d.) by mouth for 10 days.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing an Adverse Event (AE)	Up to 30 days after EOT (up to Day 40)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants Discontinuing From Study Treatment Due to an AE	Up to EOT (up to Day 10)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment.
Adjusted Percentage of Participants Meeting Clinical Response Criteria for Cure at End of Treatment (EOT)	Up to 3 days after EOT (up to Day 13)	The percentage of participants considered "cured" (i.e., ≤2 loose stools per 24 hour period for at least 2 consecutive days and no need for additional antibiotics during the 3 days following EOT) was determined in the mMITT population. A CDAD diagnosis was defined as: 1) diarrhea with a minimum of 3 unformed bowel movements (UBM) or \>200 mL volume of stool for participants with a collection device (e.g., rectal tube or colostomy bag) over 24 hours; and 2) a positive result for Clostridium difficile toxin by enzyme immunoassay (EIA), polymerase chain reaction (PCR), or a cell culture cytotoxin neutralization assay. Percentages were first stratified according to age (\<75 or ≥75 years) and number of previous CDAD episodes (0 or ≥1) and constructed using Mehrotra-Railkar continuity-corrected minimum-risk stratum weights, and the weighted averages were then derived across strata in order to calculate the adjusted percentage.

Secondary Outcome Measures

Name	Time	Method
Adjusted Percentage of Participants With Sustained Clinical Response at End of Study	Up to 40 days after EOT (up to Day 50)	The percentage of participants with sustained clinical response was determined for each arm. Sustained clinical response was declared when participants had a clinical outcome of cure at EOT, did not experience any CDAD recurrence, did not die, were not lost to follow-up, and did not have the end of study visit prior to Day 40. Percentages were first stratified according to age (\<75 or ≥75 years) and number of previous CDAD episodes (0 or ≥1) and constructed using Mehrotra-Railkar continuity-corrected minimum-risk stratum weights, and the weighted averages were then derived across strata in order to calculate the adjusted percentage.
Number of Clinical Failure Events up to Day 40	Up to 30 days after EOT (up to Day 40)	The total number of clinical failure events, which included treatment failure, CDAD recurrence, death, or being lost to follow-up, occurring during each time period was determined in each arm.