A Post-marketing, Blinded Study to Investigate How Effective Fidaxomicin is Compared to Vancomycin in the Sustained Cure of Clostridium Difficile Infection in Adults That Are Receiving Therapy to Suppress the Immune System (FREEDOM)

• Sustained clinical cure of CDI at day 26 [ Time Frame: Day 26 ] [ Designated as safety issue: No ]

  Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:

  • ≤3 unformed bowel movements for two consecutive days
  • ≥50% reduction in the number of unformed bowel movements compared to baseline; or
  • 75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
  
  

• Clinical Cure of CDI [ Time Frame: Day 12 ] [ Designated as safety issue: No ]

  Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:

  • ≤3 unformed bowel movements for two consecutive days
  • ≥50% reduction in the number of unformed bowel movements compared to baseline; or
  • 75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
  
  
• Sustained Clinical Cure of CDI at day 40 [ Time Frame: Day 40 ] [ Designated as safety issue: No ]

  Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:

  • ≤3 unformed bowel movements for two consecutive days
  • ≥50% reduction in the number of unformed bowel movements compared to baseline; or
  • 75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
  
  
• Microbial Eradication [ Time Frame: Day 12 ] [ Designated as safety issue: No ]
  Total viable count of clostridium difficile recovered from fecal specimen is below the limit of detection
  
  
• Resolution of diarrhea [ Time Frame: Day 12 ] [ Designated as safety issue: No ]
  First of two days with <3 bowel movements per day
  
  
• Use of further CDI therapy required [ Time Frame: Between Day 10 and Day 12 ] [ Designated as safety issue: No ]
  
• Number of unformed stools [ Time Frame: Between Day 10 and Day 12 ] [ Designated as safety issue: No ]
  
• >50% reduction in number of unformed stools compared to baseline [ Time Frame: Day 1 to Day 12 ] [ Designated as safety issue: No ]
  
• Recurrence of CDI [ Time Frame: Between Day 1 and Day 40 ] [ Designated as safety issue: No ]
  After TOC, re-establishment of diarrhea to an extent that is greater than the frequency recorded on the last day of study medication
  
  
• Time to recurrence of CDI [ Time Frame: Between Day 12 and Day 40 ] [ Designated as safety issue: No ]
  Time elapsing (days) from TOC to confirmed recurrence of CDI
  
  

On Day 1, subjects with diarrhea defined as having three or more unformed bowel movements or >200 mL of unformed stool (for subjects having rectal collection devices) within 24 hours, confirmed by a rapid CDI test (positive for both toxins A & B and glutamate dehydrogenase) to have CDI will be randomized to receive fidaxomicin or vancomycin (1:1 randomization).

Subjects will be treated with study medication from Day 1 to Day 10. Assessment for clinical cure (Test of Cure [TOC]) will take place 48 - 72 hours after End of Treatment (EOT). Subjects not meeting the definition of clinical cure at TOC will be defined as treatment failures.

A stool sample for evaluation of microbial cure will be taken at TOC on Day 12. Subjects meeting the criteria for clinical cure at TOC will be monitored for recurrence until 28 days after TOC (Day 40).

Treatment of subjects with recurrence of CDI will be at the discretion of the Investigator. Subjects not meeting the criteria for clinical cure at TOC will be followed for safety until Day 40. Further CDI treatment will be at the discretion of the Investigator.

The strain of Clostridium difficile will be determined for all samples.