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

NCT01598311 | Completed Phase 3 Results

• 4 other identifiers: 4261-006LCD-CDAD-11-06MK-4261-0062012-000252-34
• Study Type: interventional
• Target: 608
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Clostridium Difficile Infection

Keywords

CDAD; Clostridium difficile Associated Diarrhea; CDI; Clostridium difficile Infection; Diarrhea

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Number of Clinical Failure Events up to Day 40

  Up to 30 days after EOT (up to Day 40)

• Adjusted Percentage of Participants With Sustained Clinical Response at End of Study

  Up to 40 days after EOT (up to Day 50)

Study Arms (2)

CB-183,315

EXPERIMENTAL

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; Drug: Placebo

Vancomycin

ACTIVE COMPARATOR

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

Drug: Vancomycin

Interventions

CB-183,315 DRUG

CB-183,315 250 mg white coated tablet over-encapsulated in a size 00 opaque hard gelatin capsule.

Also known as: Surotomycin

CB-183,315

Vancomycin DRUG

Vancomycin hydrochloride 125 mg capsule over-encapsulated in size 00 opaque hard gelatin capsule.

Vancomycin

Placebo DRUG

Placebo size 00 opaque hard gelatin capsules.

CB-183,315

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

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

Related Publications (2)

• 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.

  PMID: 28961905 RESULT

• 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.

  PMID: 32747931 DERIVED

MeSH Terms

Conditions

Clostridium Infections; Diarrhea

Interventions

CB-183,315; Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: May 15, 2012
• Study Start: May 16, 2012
• Primary Completion: July 26, 2015
• Study Completion: August 25, 2015
• Last Updated: August 22, 2022
• Results First Posted: February 27, 2018

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share