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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals Holdings LLC
ClinicalTrials.gov Identifier:
NCT01085591
First received: March 9, 2010
Last updated: June 12, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Clostridium Difficile Infection
Diarrhea
Drug: CB-183,315
Drug: Placebo
Drug: Vancomycin
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 Holdings LLC:

Primary Outcome Measures:
  • Number of Participants With a Clinical Response Outcome of Clostridium Difficile Infection Cure at the End of Study Treatment [ Time Frame: Baseline (Day 0) through Study Day 19 ] [ Designated as safety issue: Yes ]
    The number of participants with an Investigator-assessed clinical response of cure is presented. The information to assess clinical response was collected at any time up to and including Day 19.

  • Number of Participants With a Clinical Response Outcome of Failure or Unable to Evaluate at the End of Study Treatment [ Time Frame: Baseline (Day 0) through Study Day 19 ] [ Designated as safety issue: No ]
    The number of participants with investigator assessed clinical response of failure or unable to evaluate is presented. Clinical response was determined by the participant's condition on the second day following the last dose of study medication, unless considered a treatment failure. Treatment failures were assessed whenever they occurred and were carried forward to the end-of-treatment (EOT). The information to assess clinical response was collected at any time up to and including Day 19.


Secondary Outcome Measures:
  • Number of Participants With a Recurrence of Clostridium Difficile Infection Through the 4-week Follow-up Period [ Time Frame: Study Day 10 up to Study Day 40 ] [ Designated as safety issue: No ]
    The number of participants with a recurrence of CDI is presented along with the number of participants without a recurrence and who were unable to be evaluated. Participants with a favorable outcome at the EOT (cure) were evaluated for recurrence of CDI. Only subjects deemed a cure at EOT were assessed for recurrence. This is the denominator used for all percentages. If diarrheal symptoms returned, participants were asked to indicate the number of unformed bowel movements (UBM) they had and have an additional C. difficile toxin test. The information to assess recurrence in participants who were deemed a cure at EOT was collected at any time during the 4-week Follow-up Period (FUP).

  • 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 [ Time Frame: Baseline (Day 0) through Study Day 12 ] [ Designated as safety issue: No ]
    The number of participants with investigator assessed clinical response of cure, failure or unable to evaluate is presented and shown separately for participants with and without infection caused by C. difficile BI/NAP1/027 strain as determined at baseline. Clinical response was determined by the participant's condition on the second day following the last dose of study medication, unless considered a treatment failure. Treatment failures were assessed whenever they occurred and were carried forward to the EOT. The information to assess clinical response for infection caused by C. difficile BI/NAP1/027 strain at Baseline was collected at any time up to and including Day 12. Strain at Baseline=SAB

  • 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 [ Time Frame: Study Day 10 up to Study Day 40 ] [ Designated as safety issue: No ]
    The number of participants with and without infection caused by C. difficile BI/NAP1/027 strain as determined at baseline with a recurrence of CDI is presented along with the number of participants without a recurrence and who were unable to be evaluated. Participants with a favorable outcome at the EOT (cure) were evaluated for recurrence of CDI. If diarrheal symptoms returned, participants were asked to indicate the number of UBM they had and have an additional C. difficile toxin test. The information to assess recurrence in participants who were deemed a cure at EOT was collected at any time during the 4-week FUP. Strain at Baseline=SAB.

  • Median Time to Resolution of Diarrhea [ Time Frame: Baseline (Day 0) through Study Day 12 ] [ Designated as safety issue: No ]
    The median time to resolution of diarrhea is presented for evaluable participants in each treatment group. The time in days from the start of treatment (time of first dose of study drug) to resolution (time of the last UBM on the day before the first of 2 consecutive days of < 4 UBMs and sustained through the second day following the last dose of study drug).


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
125 milligrams (mg) CB 183,315 administered orally twice daily, alternating with twice daily oral administration of placebo tablets, for 10 days.
Drug: CB-183,315 Drug: Placebo
Experimental: CB-183,315, 250 mg
250 mg CB 183,315 administered orally twice daily, alternating with twice daily oral administration of placebo tablets, for 10 days.
Drug: CB-183,315 Drug: Placebo
Active Comparator: Vancomycin, 125 mg
125 mg vancomycin administered orally four times a day for 10 days.
Drug: Vancomycin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 opinion of the Investigator, might interfere with study objectives
  • Life expectancy is less than 6 weeks

Additional Exclusions for Participants with Severe CDI

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

  • Age > 80
  • Hypotension, defined by sustained systolic blood pressure < 90 millimeters of mercury (mmHg), or need for vasopressors to maintain blood pressure
  • Abdominal rebound tenderness on examination
  • Acute kidney insufficiency defined by:

    • oliguria (< 20 cubic centimeter [cc] urine output per hour over a 4 hour period not responsive to attempts to increase renal perfusion) or
    • non-perfusion (for example, pre-renal) related azotemia with initial creatinine (Baseline) > 2.5 milligrams per deciliter (mg/dL) and blood urea nitrogen (BUN) > 40 mg/dL with no prior history of chronic kidney disease
  • Unable to tolerate oral medications due to persistent vomiting 2. White blood cell (WBC) count > 30,000/mm˄3
  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

  Hide Study Locations
Locations
United States, District of Columbia
Providence Hospital Clinical Research Center
Washington, District of Columbia, United States
Washington Hospital Center
Washington, District of Columbia, United States
United States, Florida
Central Florida Internists
St. Cloud, Florida, United States
United States, Georgia
Atlanta Institute for Medical Research, Inc
Decatur, Georgia, United States
Gastrointestinal Specialists of Georgia PC
Marietta, Georgia, United States
Wellstar Infectious Disease
Marietta, Georgia, United States
United States, Idaho
Idaho Falls Infectious Disease, PLLC
Idaho, Idaho, United States
United States, Illinois
University of Chicago
Chicago, Illinois, United States
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
United States, Maryland
Metropolitan Gastroentrology Group
Chevy Chase, Maryland, United States
United States, Massachusetts
Tufts University School of Medicine
Boston, Massachusetts, United States
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States
Keego Harbor, Michigan, United States, 48320
William Beaumont Hospital
Royal Oak, Michigan, United States
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States
United States, Missouri
Missouri Baptist Medical Center
St. Louis, Missouri, United States
United States, Montana
Mercury Street Medical Group - Research Group
Butte, Montana, United States
United States, New York
DiGiovanna Institute for Medical Education and Research
North Massapequa, New York, United States
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
United States, North Dakota
MeritCare Clinical Research
Fargo, North Dakota, United States
United States, Ohio
Remington Davis Inc.
Columbus, Ohio, United States
Canada, Alberta
University of Calgary, Foothills Medical Center
Calgary, Alberta, Canada
Canada, Ontario
St. Joseph Healthcare
Hamilton, Ontario, Canada
Queen's University
Kingston, Ontario, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
Canada, Quebec
Centre de Sante et des Services Sociaux de Chicoutimi
Chicoutimi, Quebec, Canada
Maisonneuve Rosemont Hospital
Montreal, Quebec, Canada
SMBD- Jewish General Hospital G-139
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Québec
Quebec City, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke
Sherbrook, Quebec, Canada
Centre hopitalier regional de Trois-Rivieres
Trois-Rivieres, Quebec, Canada
Sponsors and Collaborators
Cubist Pharmaceuticals Holdings LLC
  More Information

No publications provided

Responsible Party: Cubist Pharmaceuticals Holdings LLC
ClinicalTrials.gov Identifier: NCT01085591     History of Changes
Other Study ID Numbers: LCD-DR-09-03
Study First Received: March 9, 2010
Results First Received: April 21, 2015
Last Updated: June 12, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals Holdings LLC:
CDI
Clostridium difficile Infection
Diarrhea

Additional relevant MeSH terms:
Communicable Diseases
Infection
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015