LCD-CDAD-10-07 (CUBIST)

Purpose / Objectives

Primary Outcome

Efficacy

• To demonstrate the non-inferiority of CB-183,315 versus oral vancomycin in adult subjects with CDAD based on the difference in clinical response rates at end-of-therapy (EOT) in the mMITT population using a non inferiority margin of 10%.

Safety

• To evaluate the safety of CB-183,315 in subjects with CDAD.

Secondary Outcomes

• To demonstrate that clinical response over time (defined as clinical response through the end of therapy and the sustained clinical response from end of therapy to Day 40) to CB-183,315 is superior to oral vancomycin.

• To demonstrate that sustained clinical response to CB-183,315 at the end of the study is superior to oral vancomycin.

Diagnosis

• Clostridium-Diarrhoe (English name missing)

Target population

Age

18-89

Inclusion criteria

1. Informed Consent obtained and signed;
2. Age ≥18 and <90 years;
3. If female, subject must not be pregnant....
4. Has diarrhea with a minimum of three unformed bowel movements or >200 mL volume of stool for subjects with a collection device (eg. rectal tube or colostomy bag) over a period of 24 hours; and
5. Has a positive result for C. difficile toxin by EIA, PCR, or a cell culture cytotoxin neutralization assay from a sample obtained within 48 hours prior to first dose of study drug.

• At pre-qualified sites, a patient, who is strongly suspected of having CDAD, but the toxin result (from the sample obtained within 48 hours prior to first dose of stud drug) will not be available for up to 72 hours after the first dose of study drug, may be randomized in consultation with the Medical Monitor.

Exclusion criteria

1. Toxic megacolon and/or known small bowel ileus;
2. Received treatment with intravenous immune globulin (IVIG) within 30 days prior to the first dose of study drug;
3. Received treatment with a fecal transplant within 7 days, and/or is anticipated to receive a fecal transplant during the study.
4. Antibacterial therapy specific for current CDAD:

• Received >4 doses or >24 hours of oral vancomycin for the current episode of CDAD prior to first dose of study drug.
• Received >4 doses or >24 hours of oral/IV metronidazole for the current episode of CDAD prior to first dose of study drug unless patient received at least 3 days of such therapy, and is
  considered a treatment failure for CDAD.

• Received >24 hours of any other antibacterial for the current CDAD within 14 days prior to
  the first dose of study drug, unless considered a treatment failure for CDAD.

5. Received an investigational vaccine against C. difficile;

6. Received an investigational product containing monoclonal antibodies against toxin A or B within 180 days prior to first dose of study drug;

Note: Subjects who participated in a monoclonal antibody study and received placebo only may be enrolled into this study.

Study design

• Phase III
• Multicenter
• Two-arm
• Double-blind
• Randomized

Intervention

A 250 mg bid dose regimen of CB-183,315 will be compared with the active comparator oral vancomycin (125 mg qid)

Documents (password protected)

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Responsibilities in overall study

Sponsor

Cubist Pharmaceuticals

(National) Coordinating Investigator

Prof. Dr. med. Maria J.G.T. Vehreschild (geb. Rüping)