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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blinded, Active-Controlled Study of CB-183,315 in Patients With Clostridium Difficile Associated Diarrhea

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: CB-183,315
* Drug: Vancomycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CB-183,315<br>Participants took CB-183,315 250 mg twice daily (b.i.d.) and placebo capsules b.i.d. by mouth for 10 days. | Drug: CB-183,315<br>* CB-183,315 250 mg white coated tablet over-encapsulated in a size 00 opaque hard gelatin capsule.<br>* Other names: Surotomycin;Drug: Placebo<br>* Placebo size 00 opaque hard gelatin capsules.<br>|
| Active Comparator: Vancomycin<br>Participants took vancomycin 125 mg four times daily (q.i.d.) by mouth for 10 days. | Drug: Vancomycin<br>* Vancomycin hydrochloride 125 mg capsule over-encapsulated in size 00 opaque hard gelatin capsule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Percentage of Participants Meeting Clinical Response Criteria for Cure at End of Treatment (EOT) | 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. | Up to 3 days after EOT (up to Day 13) | 
| Percentage of Participants Experiencing an Adverse Event (AE) | 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. | Up to 30 days after EOT (up to Day 40) | 
| Percentage of Participants Discontinuing From Study Treatment Due to an AE | 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. | Up to EOT (up to Day 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Clinical Failure Events 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. | Up to 30 days after EOT (up to Day 40) | 
| Adjusted Percentage of Participants With Sustained Clinical Response at End of Study | 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. | Up to 40 days after EOT (up to Day 50) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridium difficile Associated Diarrhea, Clostridium difficile Infection, Diarrhea, CDAD, CDI