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

NCT01597505 | Completed Phase 3 Results

• 4 other identifiers: 4261-005LCD-CDAD-10-07MK-4261-0052012-000252-34
• Study Type: interventional
• Target: 606
• Locations: 0 countries
• Sites: N/A

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

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Adjusted Percentage of Participants With a Clinical Outcome of Cure at the End of Treatment (EOT)

  A clinical outcome of cure at EOT was determined by resolution of diarrhea, defined as ≤ 2 loose stools per 24-hour period for at least 2 consecutive days and the lack of need for additional antibiotics to treat the current CDAD episode after completion of the study treatment period. Participants requiring a collection device were considered to have resolution of diarrhea when the volume of stool (over a 24-hour period) was decreased by 75% as compared to baseline or the participant was no longer passing liquid stool. The estimated adjusted percentage was a weighted average across all strata, constructed using Mehrotra-Railkar continuity-corrected minimum risk (MRc) stratum weights.

  Up to 13 days

• Percentage of Participants With at Least One 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. AEs may be new events or may be pre-existing conditions that have become aggravated or have worsened in severity or frequency; or may be clinically significant changes from baseline in physical examination, laboratory tests, or other diagnostic investigation (e.g. laboratory results, x-ray findings).

  Up to Day 50

• Percentage of Participants With at Least One Serious Adverse Event (SAE)

  A SAE is any adverse experience occurring at any dose that results in any of the following outcomes: death; a life-threatening experience, referring to a situation in which the participant was at risk of death at the time of the event, requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or is considered to be an important medical event.

  Up to Day 50

• Percentage of Participants Who Discontinued 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. AEs may be new events or may be pre-existing conditions that have become aggravated or have worsened in severity or frequency; or may be clinically significant changes from baseline in physical examination, laboratory tests, or other diagnostic investigation (e.g. laboratory results, x-ray findings).

  Up to Day 13

Secondary Outcomes (10)

• Number of Participants With Clinical Response Over Time

  Up to Day 41

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

  Up to Day 50

• Adjusted Percentage of Participants With Sustained Clinical Response at Day 24

  Day 24

• Adjusted Percentage of Participants With Recurrence of CDAD at End of Study

  Up to Day 50

• Time to Resolution of Diarrhea

  Up to Day 13

Study Arms (2)

Surotomycin

EXPERIMENTAL

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

Drug: Surotomycin; Drug: Placebo

Vancomycin

ACTIVE COMPARATOR

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

Drug: Vancomycin

Interventions

Surotomycin DRUG

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

Also known as: CB-183,315

Surotomycin

Vancomycin DRUG

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

Vancomycin

Placebo DRUG

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

Surotomycin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Related Publications (2)

• 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.

  PMID: 28480267 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: May 14, 2012
• Study Start: May 16, 2012
• Primary Completion: March 20, 2015
• Study Completion: March 20, 2015
• Last Updated: July 23, 2019
• Results First Posted: February 28, 2018

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share