Phase 2
N=210
Study of CB-183,315 in Participants With Clostridium Difficile Infection
Clostridium Difficile Infection · Diarrhea
Bottom Line
View on ClinicalTrials.gov: NCT01085591 ↗Enrolled (actual)
210
Serious AEs
14.0%
Results posted
Jun 2015
Primary outcome: Primary: Number of Participants With a Clinical Response Outcome of Clostridium Difficile Infection Cure at the End of Study Treatment — 61; 58; 59 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- CB-183,315 (Drug); Placebo (Drug); Vancomycin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Primary completion
- Apr 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With a Clinical Response Outcome of Clostridium Difficile Infection Cure at the End of Study Treatment |
61; 58; 59 | — |
| PRIMARY Number of Participants With a Clinical Response Outcome of Failure or Unable to Evaluate at the End of Study Treatment |
3; 5; 4; 2; 4; 3 | — |
| SECONDARY Number of Participants With a Recurrence of Clostridium Difficile Infection Through the 4-week Follow-up Period |
17; 10; 21; 44; 47; 37 | — |
| SECONDARY Number of Participants With a Clinical Response Outcome at the End of Study Treatment With and Without Infection Caused by C. Difficile BI/NAP1/027 Strain at Baseline |
15; 15; 21; 1; 4; 1 | — |
| SECONDARY Number of Participants With a Recurrence of Clostridium Difficile Infection at the End of Study Treatment With and Without Infection Caused by C. Difficile BI/NAP1/027 Strain at Baseline |
5; 5; 11; 10; 9; 10 | — |
| SECONDARY Median Time to Resolution of Diarrhea |
1.5; 1.4; 2.1 | — |
Summary
This is a randomized, double-blind, single-placebo, active-controlled, dose ranging parallel group design with 3 arms. Two dose regimens of CB-183,315 dosed twice daily will be compared with the active comparator oral vancomycin (125 milligrams (mg ) four times daily). Participants with diarrhea at risk for Clostridium difficile infection (CDI) [for example, received prior or concomitant antibiotic(s)] will be identified and tested for C. difficile toxin in stool using an enzyme immunoassay (EIA), or polymerase chain reaction (PCR) per the usual standard of care. Eligible participants will be consented, undergo baseline evaluations, and will be randomized in a blinded fashion to one of 3 treatment arms.
Participants will be randomized to receive either 125 mg CB-183,315 twice daily alternating with placebo tablets twice daily, 250 mg CB-183,315 twice daily alternating with placebo tablets twice daily or 125 mg oral vancomycin four times dailyover a period of 10 days in a 1:1:1 fashion.
Eligibility Criteria
To be eligible for enrollment, a participant must meet all of the following criteria prior to any study related procedures:
- Informed Consent obtained and signed
- Age ≥ 18 years
- If female, participant is non-lactating, and is either:
- Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy
- Of childbearing potential and is practicing the barrier method of birth control along with one of the following methods: oral or parenteral contraceptives for 3 months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse
- Established non-severe or severe CDI (after Data Monitoring Committee [DMC] review) with a positive stool test for toxin A and/or B within 72 hours prior to first dose of study drug.
Exclusion Criteria
A participant will not be enrolled if s/he meets any of the following criteria:
- Female and pregnant or lactating
- Toxic megacolon and/or known small bowel ileus
- Received treatment with intravenous (IV) immune globulin within 30 days prior to the first dose of study drug
- Antibacterial therapy specific for current CDI or that may be effective for CDI even if given for a different indication:
- Received more than 24 hours of oral vancomycin for the current episode of CDI prior to first dose of study drug.
- Received more than 24 hours of oral/intravenous metronidazole OR any other therapy specific for the current episode of CDI immediately prior to first dose of study drug unless the participant received at least 3 days of such therapy, and is considered a treatment failure for CDI.
- Received more than 24 hours of oral/intravenous metronidazole for any other indication in the 3 days prior to first dose of study drug.
- Participants with more than 2 episodes of CDI within 90 days (that is, participants can be enrolled with their 1st recurrence/2nd episode)
- Major gastrointestinal (GI) surgery (that is, significant bowel resection including total colectomy with ileostomy) within 3 months of enrollment (this does not include appendectomy or cholecystectomy)
- History of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis
- Unable to stop loperamide, diphenoxylate, and cholestyramine during the duration of the study
- Unable to stop opiate treatment, unless on a stable dose as of onset of diarrhea and no change in dose planned for the duration of the study
- Known positive stool cultures for other enteropathogens, including but not limited to Salmonella, Shigella and Campylobacter
- Known stool studies positive for ova and/or parasites
- Known intolerance or hypersensitivity to daptomycin and/or vancomycin
- Poor concurrent medical risks with clinically significant co-morbid disease such that in the opinion of the Investigator the participant should not be enrolled
- Received an investigational drug or participated in any experimental procedure within 1 month prior to study entry
- Previously enrolled in this study
- Received an investigational vaccine against C. difficile
- Participants with known Hepatitis B or Hepatitis C who have alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal (ULN) and/or bilirubin > 1.5 times the ULN
- Human immunodeficiency virus positive, unless controlled (that is, on triple therapy) and with a CD4 > 200 cells per millimeter cubed (cellsmm˄3)
- Anticipated that systemic antibacterial therapy for a non-CDI infections will be required for >7 days after start of study therapy
- Concurrent therapy with daptomycin
- Unable to discontinue Saccharomyces or similar probiotic
- Known active IV drug or alcohol abuse
- Concurrent intensive chemotherapy, radiotherapy or biologic treatment for active malignancy (may only be enrolled after consultation with Medical Monitor)
- Unable to comply with the protocol requirements
- Any condition that, in the op
Data sourced from ClinicalTrials.gov (NCT01085591). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.