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)

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Clostridium Difficile-Associated Diarrhea (CDAD)	Drug: fidaxomicin; Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	611 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, 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
Actual Study Start Date :	October 10, 2012
Actual Primary Completion Date :	March 18, 2015
Actual Study Completion Date :	April 16, 2015

Arms and Interventions

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Arm	Intervention/treatment
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.

Outcome Measures

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Primary Outcome Measures :

1. 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 ]
   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 :

1. 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 ]
   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.
2. 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 ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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Sponsors and Collaborators

Optimer Pharmaceuticals LLC

Investigators

Study Director:	Medical Director	Merck Sharp & Dohme Corp.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Optimer Pharmaceuticals LLC
ClinicalTrials.gov Identifier:	NCT01691248 History of Changes
Other Study ID Numbers:	5119-001; OPT-80-302 ( Other Identifier: Optimerpharma Study Number )
First Posted:	September 24, 2012
Results First Posted:	April 12, 2016
Last Update Posted:	May 1, 2017
Last Verified:	March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

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; Fluoroquinolones; Anti-Bacterial Agents	Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action