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Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)

Phase 4
Completed
Conditions
Inflammatory Bowel Disease (IBD)
Clostridium Difficile Infection (CDI)
Interventions
Registration Number
NCT02437591
Lead Sponsor
Astellas Pharma Europe Ltd.
Brief Summary

The purpose of this study is to investigate the plasma pharmacokinetics (PK) of fidaxomicin (FDX) and primary metabolite OP-1118 in Subjects with Inflammatory Bowel Disease (IBD) and C. difficile Infection (CDI).

This study will also compare CDI clinical response to the microbiological response in terms of magnitude of reduction of C. difficile total viable count and spore count during treatment with FDX and if achieved; the time to microbial eradication; determine time to negative CDI toxin assay in stool specimens during treatment with FDX; assess the stool concentrations of FDX and metabolite OP-1118 throughout therapy; assess the length of hospital stay, readmissions and resource utilization for IBD patients receiving FDX; record the incidence and severity of Adverse Events (AEs) and document the impact of treatment on Quality of Life as measured by the changes in Short Inflammatory Bowel Disease Questionnaire (IBDQ) score.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
Inclusion Criteria
  • Confirmed diagnosis or history of IBD for at least 3 months

  • Subject has have active IBD defined by :

    • partial MAYO score (ulcerative colitis subjects) of 2 or more, where at least 1 point has to originate from blood in stool
    • Harvey-Bradshaw Index (HBI) (Crohn's disease subjects) of 5 or more, excluding points for complications
  • CDI confirmed positive according to local standard testing for the presence of C. difficile within 48 hr prior to enrollment

  • Female subject is not breastfeeding at Screening or while participating in this study

  • Subject agrees to practice effective birth control from Screening and while participating in this study

  • Subject agrees not to participate in another interventional study while participating in this study

  • Male partner agrees not to donate sperm starting at screening and throughout the investigational period.

Exclusion Criteria
  • Subject has received more than one day of dosing of any CDI therapy within the 48 hrs prior to enrollment
  • Subject is unable to swallow oral study medication
  • Presence of an ostomy or short bowel syndrome
  • Subject has a current diagnosis of toxic megacolon
  • Subject is not willing to adhere to the provisions of treatment and observation specified in the protocol
  • Subject has been enrolled into this study previously, has taken any investigational drug within 28 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently participating in another clinical study which may influence the assessment of efficacy and/or safety endpoints of this study, in the opinion of the Sponsor
  • Subject has previously participated in a CDI vaccine study
  • Subject has hypersensitivity to FDX or any of its components
  • Subject has a condition which, in the Investigator's opinion, makes the Subject unsuitable for study participation

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
fidaxomicinfidaxomicintablet twice daily
Primary Outcome Measures
NameTimeMethod
Pharmacokinetic parameter of fidaxomicin: Area under the curve from 0 to 12 hrs (AUC12)Day 1
Pharmacokinetic parameter of fidaxomicin: Maximum plasma concentration (Cmax)Day 1, Day 5 and Day 10
Pharmacokinetic parameter of OP-1118: Maximum plasma concentration (Cmax)Day 1, Day 5 and Day 10
Pharmacokinetic parameter of OP-1118: Area under the curve from 0 to 12 hrs (AUC12)Day 1
Pharmacokinetic parameter of fidaxomicin and OP-1118: Metabolite to Parent Ratio (MPR)Day 1
Pharmacokinetic parameter of fidaxomicin: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau)Day 5 and Day 10
Pharmacokinetic parameter of OP-1118: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau)Day 5 and Day 10
Pharmacokinetic parameter of fidaxomicin: The time after dosing when Cmax occurs (tmax)Day 1, Day 5 and Day 10
Pharmacokinetic parameter of OP-1118: The time after dosing when Cmax occurs (tmax)Day 1, Day 5 and Day 10
Pharmacokinetic parameter of OP-1118: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)Day 5 and Day 10
Pharmacokinetic parameter of fidaxomicin: Concentration immediately prior to dosing at multiple dosing (Ctrough)Day 5 and Day 10
Pharmacokinetic parameter of OP-1118: Concentration immediately prior to dosing at multiple dosing (Ctrough)Day 5 and Day 10
Pharmacokinetic parameter of fidaxomicin: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)Day 5 and Day 10
Secondary Outcome Measures
NameTimeMethod
CDI clinical responseDay 12
Microbiological response of C. difficile total viable count, spore count, microbiological eradication and negative CDI toxin assayDay 5 and Day 10
Stool concentrations of fidaxomicin and its metabolite OP-1118Day 1, Day 5 and Day 10
Length of hospital stay, readmissions and resource utilizationup to Day 180
Safety as assessed by incidence and severity of adverse eventsup to Day 180
Health related quality of life as assessed by short IBDQ scoreDay 10, Day 26, Day 40, Day 90 and Day 180

Inflammatory Bowel Disease Questionnaire (IBDQ)

Trial Locations

Locations (12)

Site AT43001

🇦🇹

Graz, Austria

Site RU70002

🇷🇺

Moscow, Russian Federation

Site PL48002

🇵🇱

Warszawa, Poland

Site GR30004

🇬🇷

Athens, Greece

Site RU70003

🇷🇺

Moscow, Russian Federation

Site IT39003

🇮🇹

Padova, Italy

Site FR33001

🇫🇷

Paris, France

Site FR33002

🇫🇷

Clichy, France

Site RU70001

🇷🇺

Saint Petersburg, Russian Federation

Site GB44002

🇬🇧

London, United Kingdom

Site PL48003

🇵🇱

Warsaw, Poland

Site IT39001

🇮🇹

Roma, Italy

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