Clinical trial NCT01597505: Study of CB-183,315 in Participants With Clostridium Difficile Associated Diarrhea (MK-4261-005)
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: 2012-05-14
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Adjusted Percentage of Participants With a Clinical Outcome of Cure at the End of Treatment (EOT)
timeFrame: Up to 13 days
measure: Percentage of Participants With at Least One Adverse Event (AE)
timeFrame: Up to Day 50
measure: Percentage of Participants With at Least One Serious Adverse Event (SAE)
timeFrame: Up to Day 50
measure: Percentage of Participants Who Discontinued Treatment Due to an AE
timeFrame: Up to Day 13
Secondary outcomes:
measure: Number of Participants With Clinical Response Over Time
timeFrame: Up to Day 41
measure: Adjusted Percentage of Participants With Sustained Clinical Response at the End of Study
timeFrame: Up to Day 50
measure: Adjusted Percentage of Participants With Sustained Clinical Response at Day 24
timeFrame: Day 24
measure: Adjusted Percentage of Participants With Recurrence of CDAD at End of Study
timeFrame: Up to Day 50
measure: Time to Resolution of Diarrhea
timeFrame: Up to Day 13
measure: Time to Reappearance of Diarrhea From End of Treatment to the End of Study
timeFrame: Up to Day 50
measure: Adjusted Percentage of Participants With a Clinical Response at the End of Treatment for Infections Deemed to be Caused by the C. Difficile BI/NAP1/027 Strain at Baseline
timeFrame: Up to Day 13
measure: Adjusted Percentage of Participants Per Protocol 1 Population With a Clinical Response at the End of Treatment
timeFrame: Up to Day 13
measure: Adjusted Percentage of Participants With a Sustained Clinical Response at the End of Study for Infections Deemed to be Caused by the C. Difficile BI/NAP1/027 Strain at Baseline
timeFrame: Up to Day 50
measure: Adjusted Percentage of Participants From the Per Protocol 2 Population With a Sustained Clinical Response at the End of Study
timeFrame: Up to Day 50
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
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.