Safety and Efficacy Study of VP20621 for Prevention of Recurrent Clostridium Difficile Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01259726
First received: December 9, 2010
Last updated: February 11, 2015
Last verified: March 2014
  Purpose

The objectives of this study are: (1) to evaluate the safety and tolerability of VP 20621 dosed orally for up to 14 days in adults previously treated for CDI; (2) to characterize the frequency and duration of stool colonization with the VP 20621 strain of C. difficile; (3) to evaluate the efficacy of VP 20621 for prevention of recurrence of CDI; and (4)to select a dose regimen of VP 20621 to be used in future studies.


Condition Intervention Phase
Clostridium Difficile Infection
Biological: VP20621
Other: Placebo
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: Prevention
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Assess the Safety and Efficacy of VP 20621 for Prevention of Recurrence of Clostridium Difficile Infection (CDI) in Adults Previously Treated for CDI

Further study details as provided by Shire:

Primary Outcome Measures:
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 7 days after the last dose of study drug (up to Week 3) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurring in a study participant, regardless of causal relationship. TEAEs were defined as all AEs that start during the study drug treatment period (and up to 7 days after the last dose of the study drug) and were not seen at baseline, or were seen at baseline but increased in frequency and/or severity during the study drug treatment period (and up to 7 days after the last dose of study drug). SAE was any AE that results in any of the following outcomes: death, a life-threatening event, inpatient hospitalization or prolongation of an existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, other medically important events based upon appropriate medical judgement.

  • Number of Participants With Positive Clostridium Difficile Stool Cultures Demonstrating Non-Toxigenic Clostridium Difficile-Strain M3 [ Time Frame: After study drug administration period (14 days) through Week 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants With Clostridium Difficile Infection (CDI) Recurrence [ Time Frame: Baseline (Day 1) up to Week 6 ] [ Designated as safety issue: No ]
    CDI recurrence was defined as at least 1 event characterized by ALL of the following: >=3 unformed (loose or watery) stools within 24 hours (data derived from Diarrhea case report form (CRF) page which was to be completed for any clinical event of diarrhea or loose/watery stool occurring between Day 1 and Week 6); a positive C. difficile stool assay, or pseudomembranes on endoscopy/surgery; and no other likely cause of the diarrhea in the opinion of the investigator.

  • Number of Participants With Use of Antibacterial Treatment for CDI [ Time Frame: Baseline (Day 1) up to Week 6 ] [ Designated as safety issue: No ]
    Any antibacterial medication used after Day 1 for which the investigator selected the indication "antibacterial for C. difficile infection".

  • Number of Participants With Clinical Events of Diarrhea or Loose/Watery Stools [ Time Frame: Baseline (Day 1) up to Week 6 ] [ Designated as safety issue: No ]
    Data were derived from all AEs starting on or after Day 1 for which a Diarrhea CRF page was completed.

  • Time to First CDI Recurrence [ Time Frame: Baseline (Day 1) up to Week 6 ] [ Designated as safety issue: No ]
    CDI recurrence was defined as at least 1 event characterized by ALL of the following: >=3 unformed (loose or watery) stools within 24 hours (data derived from Diarrhea CRF page which was to be completed for any clinical event of diarrhea or loose/watery stool occurring between Day 1 and Week 6); a positive C. difficile stool assay, or pseudomembranes on endoscopy/surgery; and no other likely cause of the diarrhea in the opinion of the investigator. Time of onset is from date of randomization to date of first CDI recurrence. Time to first CDI recurrence was assessed using Kaplan-Meier curve. Due to small number of subjects (<50%) with CDI recurrence, median time to event was not evaluable.


Enrollment: 173
Study Start Date: May 2011
Study Completion Date: July 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Other: Placebo
10 mL placebo once daily for 14 days
Experimental: VP20621 Low Dose and Placebo Biological: VP20621
VP20621 as oral liquid once daily for 7 days followed by placebo as oral liquid once daily for seven days
Other: Placebo
10 mL placebo once daily for 14 days
Experimental: VP20621 High Dose and Placebo Biological: VP20621
VP20621 as oral liquid once daily for 7 days followed by placebo as oral liquid once daily for 7 days
Other: Placebo
10 mL placebo once daily for 14 days
Experimental: VP20621 High Dose Biological: VP20621
VP20621 as oral liquid once daily for 14 days

  Eligibility

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

Inclusion Criteria:

  1. Adult subjects, 18 years of age and over, who understand the risks and benefits of participation and have provided written informed consent for the study.
  2. Subjects who are experiencing a first event or first recurrence of clostridium difficile (CDI) within the last 28 days and have been successfully treated with an antibiotic for CDI.
  3. Subjects who are medically stable.
  4. Subjects who are willing and able to comply with the study procedures and visit schedules outlined.
  5. If female be post-menopausal, surgically sterile or agree to follow an acceptable method of birth control.

Exclusion Criteria:

  1. Subjects who have had more than 2 episodes of CDI within the last 6 months.
  2. Subjects who have been diagnosed with Inflammatory Bowel Disease,active Irritable Bowel Syndrome, celiac disease, active gastroparesis, toxic megacolon.
  3. GI surgery within 6 weeks before the day of randomization
  4. Have known immunodeficiency disorder, such as HIV Infection
  5. Pregnant or breast feeding females.
  6. Concurrent acute life-threatening diseases.
  7. Inability to tolerate oral liquids.
  8. Have an absolute neutrophil count < 1000/mm3 at screening
  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: NCT01259726

  Show 59 Study Locations
Sponsors and Collaborators
Shire
Investigators
Study Director: Steve Villano, MD ViroPharma
  More Information

No publications provided by Shire

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01259726     History of Changes
Other Study ID Numbers: VP20621-200, 2010-020484-20
Study First Received: December 9, 2010
Results First Received: January 20, 2015
Last Updated: February 11, 2015
Health Authority: United States: Food and Drug Administration
Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Ethics Commission
Germany: Paul-Ehrlich-Institut
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica
Switzerland: Ethikkommission
Switzerland: Swissmedic

Keywords provided by Shire:
Diarrhea
Clostridium difficile
Clostridium infections
Signs and Symptoms Digestive
Bacterial Infections
Pharmacologic Actions

Additional relevant MeSH terms:
Communicable Diseases
Infection

ClinicalTrials.gov processed this record on May 26, 2015