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

NCT ID: NCT01597505

Last Updated: 2019-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 606 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-16
• Study Completion Date: 2015-03-20

Brief Summary

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.

Conditions

Clostridium Difficile Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Surotomycin

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

Group Type: EXPERIMENTAL

Surotomycin

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Placebo for Surotomycin over-encapsulated tablet administered orally, twice daily for 10 days

Vancomycin

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

Group Type: ACTIVE_COMPARATOR

Vancomycin

Intervention Type: DRUG

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

Interventions

Surotomycin

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

Intervention Type: DRUG

Vancomycin

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

Intervention Type: DRUG

Placebo

Placebo for Surotomycin over-encapsulated tablet administered orally, twice daily for 10 days

Intervention Type: DRUG

Other Intervention Names

CB-183,315

Eligibility Criteria

Inclusion 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Boix V, Fedorak RN, Mullane KM, Pesant Y, Stoutenburgh U, Jin M, Adedoyin A, Chesnel L, Guris D, Larson KB, Murata Y. Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With Clostridium difficile Infection. Open Forum Infect Dis. 2017 Jan 19;4(1):ofw275. doi: 10.1093/ofid/ofw275. eCollection 2017 Winter.

Reference Type: RESULT

PMID: 28480267 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32747931 (View on PubMed)

Other Identifiers

LCD-CDAD-10-07

Identifier Type: OTHER

Identifier Source: secondary_id

MK-4261-005

Identifier Type: OTHER

Identifier Source: secondary_id

2012-000252-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

4261-005

Identifier Type: -

Identifier Source: org_study_id