Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001) - Full Text View

Purpose

The objective of this study is to demonstrate the efficacy and safety of Fidaxomicin versus placebo for prophylaxis against Clostridium difficile-Associated Diarrhea (CDAD) in adult participants undergoing hematopoietic stem cell transplantation (HSCT). The primary hypothesis is that Fidaxomicin is superior to placebo in preventing CDAD in participants undergoing HSCT.

Condition	Intervention	Phase
Clostridium Difficile-Associated Diarrhea (CDAD)	Drug: fidaxomicin Drug: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	DEFLECT-1: A Phase 3b Multi-Center, Double-Blind, Randomized, Placebo Controlled Study to Demonstrate the Safety and Efficacy of Fidaxomicin for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Diarrhea

Drug Information available for: Fidaxomicin

U.S. FDA Resources

Further study details as provided by Optimer Pharmaceuticals LLC:

Primary Outcome Measures:

Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up. [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]
CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.

Secondary Outcome Measures:

Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 60 Days Post-treatment. [ Time Frame: Up to 60 days post-treatment ] [ Designated as safety issue: No ]
CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to Day 70 of Study. [ Time Frame: Up to Day 70 of study ] [ Designated as safety issue: No ]
CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.


Enrollment:	611
Study Start Date:	October 2012
Study Completion Date:	April 2015
Primary Completion Date:	March 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Fidaxomicin 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Drug: fidaxomicin Fidaxomicin 200 mg tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Study drug treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later). Study drug treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days. Other Names: DIFICID DIFICLIR OPT-80 PAR-101
Placebo Comparator: Placebo Placebo tablet once daily for no longer than 40 days	Drug: Placebo Placebo tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later). Treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.

Arms

Assigned Interventions

Active Comparator: Fidaxomicin

200 mg Fidaxomicin tablet once daily for no longer than 40 days

Drug: fidaxomicin

Fidaxomicin 200 mg tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Study drug treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later).

Study drug treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.

Other Names:

DIFICID
DIFICLIR
OPT-80
PAR-101

Placebo Comparator: Placebo

Placebo tablet once daily for no longer than 40 days

Drug: Placebo

Placebo tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later).

Treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female 18 years of age or older.
Females of childbearing potential must be using an adequate and reliable method of contraception (e.g., abstinence, barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). Males and females must agree to avoid conception during treatment and for four weeks following the end of study treatment.
Is undergoing HSCT with planned Fluoroquinolone prophylaxis.
Informed consent is provided.

Exclusion Criteria:

Ongoing active CDAD infection (as evidenced by clinical signs of diarrhea along with the presence of either toxin A and/or B [or their respective genes, tcdA and/or tcdB] of C. difficile in the stool) or current treatment for CDAD.
Undergoing cord blood transplants.
Has fulminant colitis, toxic megacolon, or ileus.
A history of inflammatory bowel disease (ulcerative colitis or Crohn's disease).
Women who are pregnant or are actively breast feeding (all women of childbearing potential must have a negative pregnancy test result prior to dosing study drug).
Use of any drugs potentially useful in the treatment of CDAD (e.g. oral Vancomycin, Metronidazole, oral Bacitracin, Fusidic Acid, Rifaximin, and Nitazoxanide).
Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant in the study, would make it unlikely for the participant to complete the study, or would confound the results of the study.
Participation in other clinical research studies utilizing an investigational agent within one month prior to screening and during the study treatment period.

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: NCT01691248

Sponsors and Collaborators

Optimer Pharmaceuticals LLC

Investigators


Study Director:	Medical Director	Merck Sharp & Dohme Corp.

More Information


Responsible Party:	Optimer Pharmaceuticals LLC
ClinicalTrials.gov Identifier:	NCT01691248 History of Changes
Other Study ID Numbers:	5119-001 OPT-80-302
Study First Received:	September 19, 2012
Results First Received:	March 11, 2016
Last Updated:	March 11, 2016
Health Authority:	United States: Food and Drug Administration Canada: Health Canada

Keywords provided by Optimer Pharmaceuticals LLC:


Clostridium difficile Clostridium difficile-Associated Diarrhea Prophylaxis Hematopoietic Stem Cell Transplantation

Additional relevant MeSH terms:


Diarrhea Signs and Symptoms, Digestive Signs and Symptoms

ClinicalTrials.gov processed this record on September 30, 2016

Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001) (DEFLECT-1)