Study of CB-183,315 in Patients With Clostridium Difficile Infection

This study has been completed.
Sponsor:
Information provided by:
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01085591
First received: March 9, 2010
Last updated: May 12, 2011
Last verified: May 2011
  Purpose

This is a randomized, double-blind, single-dummy, active-controlled, dose ranging parallel group design with 3 arms. Two dose regimens of CB-183,315 dosed bid will be compared with the active comparator oral vancomycin (125 mg qid). Subjects with diarrhea at risk for CDI [e.g. 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 subjects will be consented, undergo baseline evaluations and will be randomized in a blinded fashion to one of 3 treatment arms.

Approximately 210 patients will be randomized to receive either 125 mg CB 183,315 bid alternating with dummy tablets bid, 250 mg CB-183,315 bid alternating with dummy tablets BID or 125 mg oral vancomycin qid over a period of 10 days in a 1:1:1 fashion.


Condition Intervention Phase
Clostridium Difficile Infection
Diarrhea
Drug: CB-183,315
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blinded, Active-Controlled, Dose Ranging Study of CB-183,315 in Patients With Clostridium Difficile Infection.

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • To assess the safety of each of two oral dose regimens of CB-183,315 and oral vancomycin in subjects with CDI and to assess the relative efficacy of each of two oral dose regimens of CB-183,315 and oral vancomycin in subjects with CDI. [ Time Frame: End of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the relative CDI recurrence rate in responders within 4 weeks after treatment completion of each of two dose regimens of CB-183,315 and oral vancomycin. [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • To assess the relative efficacy of each of two oral dose regimens of CB-183,315 and oral vancomycin for CDI infection caused by C. difficile 027 strain [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • To assess CDI recurrence rate within 4 weeks after treatment completion for infection with C. difficile 027 strain for each of two dose regimens of CB-183,315 and oral vancomycin. [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • To assess the time to resolution of diarrhea of each of two dose regimens of CB-183,315 and oral vancomycin [ Time Frame: End of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 210
Study Start Date: April 2010
Study Completion Date: May 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CB-183,315, 125 mg Drug: CB-183,315
CB-183,315 125 mg bid for 10 days CB-183,315 250 mg bid for 10 days oral vancomycin 125 mg qid for 10 days
Experimental: CB-183,315, 250 mg Drug: CB-183,315
CB-183,315 125 mg bid for 10 days CB-183,315 250 mg bid for 10 days oral vancomycin 125 mg qid for 10 days
Active Comparator: oral vancomycin, 125 mg Drug: CB-183,315
CB-183,315 125 mg bid for 10 days CB-183,315 250 mg bid for 10 days oral vancomycin 125 mg qid for 10 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible for enrollment, a subject must meet all of the following criteria prior to any study related procedures:

  1. Informed Consent obtained and signed;
  2. Age ≥ 18 years;
  3. If female, subject is non-lactating, and is either:

    • Not of childbearing potential, defined as postmenopausal for at least one 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 three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse.
  4. Established non-severe or severe CDI (after DMC review) with a positive stool test for toxin A and/or B within 72 hours prior to first dose of study drug; Note: Patients with severe C. difficile infection must not be enrolled in the beginning of the study. Severe patients can only be enrolled after written notification by the DMC Chair has been received by the Sponsor.

Exclusion Criteria:

A subject will not be enrolled if s/he meets any of the following criteria:

  1. Female and pregnant or lactating;
  2. Toxic megacolon and/or known small bowel ileus;
  3. Received treatment with intravenous immune globulin (IVIG) within 30 days prior to the first dose of study drug;
  4. Antibacterial therapy specific for current CDI:

    • Received more than 24 hours of oral/IV metronidazole for the current episode of CDI prior to first dose of study drug unless patient received at least 3 days of oral/IV metronidazole, and is considered a failure.
    • 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 any other antibacterial therapy specific for current CDI within 14 days prior first dose of study drug, unless considered a failure.
  5. Patients with more than 2 episodes of CDI within 90 days (i.e., patients can be enrolled with their 1st recurrence/2nd episode);
  6. Major GI surgery (i.e. significant bowel resection) within 3 months of enrollment (this does not include appendectomy or cholecystectomy);
  7. History of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis;
  8. Unable to stop loperamide, diphenoxylate, and cholestyramine during the duration of the study;
  9. 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;
  10. Known positive stool cultures for other enteropathogens, including but not limited to Salmonella, Shigella and Campylobacter;
  11. Known stool studies positive for ova and/or parasites;
  12. Known intolerance or hypersensitivity to daptomycin and/or vancomycin;
  13. Poor concurrent medical risks with clinically significant co-morbid disease such that in the opinion of the Investigator the patient should not be enrolled;
  14. Received an investigational drug or participated in any experimental procedure within 1 month prior to study entry;
  15. Previously enrolled in this study;
  16. Received an investigational vaccine against C. difficile;
  17. Subjects with known Hepatitis B or Hepatitis C who have ALT or AST >2.5 X ULN and/or Bilirubin > 1.5 X ULN;
  18. HIV positive, unless controlled (i.e., on triple therapy) and with a CD4 >200 cells/mm3;
  19. Anticipated that systemic antibacterial therapy for a non-CDI infections will be required for >7 days after start of study therapy;
  20. Concurrent therapy with daptomycin;
  21. Unable to discontinue Saccharomyces or similar probiotic;
  22. Known active IV drug or alcohol abuse;
  23. Concurrent intensive chemotherapy, radiotherapy or biologic treatment for active malignancy (may only be enrolled after consultation with Medical Monitor);
  24. Unable to comply with the protocol requirements;
  25. Any condition that, in the opinion of the Investigator, might interfere with study objectives;
  26. Life expectancy is less than 6 weeks.

Additional Exclusions for Subjects with Severe CDI

In addition to the criteria listed above, a subject who meets the definition of severe CDI will not be enrolled if the subject meets any of the following criteria:

  1. Age >80;
  2. Hypotension, defined by sustained systolic blood pressure <90 mmHg, or need for vasopressors to maintain blood pressure;
  3. Abdominal rebound tenderness on examination;
  4. Acute kidney insufficiency defined by:

    • oliguria (< 20 cc urine output per hour over a 4 hour period not responsive to attempts to increase renal perfusion) OR
    • non-perfusion (e.g. pre-renal) related azotemia with initial creatinine (Study Baseline) > 2.5 mg/dL and BUN >40 mg/dL with no prior history of chronic kidney disease;
  5. Unable to tolerate oral medications due to persistent vomiting;
  6. WBC > 30,000/mm3.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01085591

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Sponsors and Collaborators
Cubist Pharmaceuticals
  More Information

No publications provided

Responsible Party: Ian Freidland, Cubist Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01085591     History of Changes
Other Study ID Numbers: LCD-DR-09-03
Study First Received: March 9, 2010
Last Updated: May 12, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals:
CDI
Clostridium difficile Infection
Diarrhea

Additional relevant MeSH terms:
Diarrhea
Clostridium Infections
Signs and Symptoms, Digestive
Signs and Symptoms
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on July 22, 2014