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

NCT01691248 | Completed Phase 3 Results DMC

• 2 other identifiers: 5119-001OPT-80-302
• Study Type: interventional
• Target: 611
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Clostridium Difficile-Associated Diarrhea (CDAD)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up.

  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.

  Up to 30 days post-treatment

Secondary Outcomes (2)

• Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 60 Days Post-treatment.

  Up to 60 days post-treatment

• Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to Day 70 of Study.

  Up to Day 70 of study

Study Arms (2)

Fidaxomicin

ACTIVE COMPARATOR

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

Drug: fidaxomicin

Placebo

PLACEBO COMPARATOR

Placebo tablet once daily for no longer than 40 days

Drug: Placebo

Interventions

fidaxomicin DRUG

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.

Also known as: DIFICID, DIFICLIR, OPT-80, PAR-101

Fidaxomicin

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Optimer Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Related Publications (2)

• de Almeida C, Wong M, Kleijn HJ, Wrishko RE. Predicted Bezlotoxumab Exposure in Patients Who Have Received a Hematopoietic Stem Cell Transplant. Clin Ther. 2023 Apr;45(4):356-362. doi: 10.1016/j.clinthera.2023.02.006. Epub 2023 Mar 9.

  PMID: 36906440 DERIVED

• Mullane KM, Winston DJ, Nooka A, Morris MI, Stiff P, Dugan MJ, Holland H, Gregg K, Adachi JA, Pergam SA, Alexander BD, Dubberke ER, Broyde N, Gorbach SL, Sears PS. A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation. Clin Infect Dis. 2019 Jan 7;68(2):196-203. doi: 10.1093/cid/ciy484.

  PMID: 29893798 DERIVED

MeSH Terms

Interventions

Fidaxomicin; OPT 80

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Polyketides; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2012
• First Posted: September 24, 2012
• Study Start: October 10, 2012
• Primary Completion: March 18, 2015
• Study Completion: April 16, 2015
• Last Updated: September 18, 2018
• Results First Posted: April 12, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share