Clinical trial NCT01598311: A Study of CB-183,315 in Participants With Clostridium Difficile Associated Diarrhea (MK-4261-006)
Official title: A Randomized, Double-Blinded, Active-Controlled Study of CB-183,315 in Patients With Clostridium Difficile Associated Diarrhea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Difficile Infection
Keywords: CDAD
Clostridium difficile Associated Diarrhea
CDI
Clostridium difficile Infection
Diarrhea
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2012-05-15
Enrollment: 608
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adjusted Percentage of Participants Meeting Clinical Response Criteria for Cure at End of Treatment (EOT)
timeFrame: Up to 3 days after EOT (up to Day 13)
measure: Percentage of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 30 days after EOT (up to Day 40)
measure: Percentage of Participants Discontinuing From Study Treatment Due to an AE
timeFrame: Up to EOT (up to Day 10)
Secondary outcomes:
measure: Number of Clinical Failure Events up to Day 40
timeFrame: Up to 30 days after EOT (up to Day 40)
measure: Adjusted Percentage of Participants With Sustained Clinical Response at End of Study
timeFrame: Up to 40 days after EOT (up to Day 50)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Daley P, Louie T, Lutz JE, Khanna S, Stoutenburgh U, Jin M, Adedoyin A, Chesnel L, Guris D, Larson KB, Murata Y. Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial. J Antimicrob Chemother. 2017 Dec 1;72(12):3462-3470. doi: 10.1093/jac/dkx299.
citation: Cheknis A, Devaris D, Chesnel L, Dale SE, Nary J, Sambol SP, Citron DM, Goering RV, Johnson S. Characterization of Clostridioides difficile isolates recovered from two Phase 3 surotomycin treatment trials by restriction endonuclease analysis, PCR ribotyping and antimicrobial susceptibilities. J Antimicrob Chemother. 2020 Nov 1;75(11):3120-3125. doi: 10.1093/jac/dkaa297.