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

Study Overview
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Brief Summary
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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.

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

Conditions
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Inflammatory Bowel Disease (IBD), Clostridium Difficile Infection (CDI)

Intervention / Treatment
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* Drug: fidaxomicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fidaxomicin<br>tablet twice daily | Drug: fidaxomicin<br>* oral<br>* Other names: ASP2819;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 fidaxomicin: Area under the curve from 0 to 12 hrs (AUC12) |  | Day 1 | 
| 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 fidaxomicin: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F) |  | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CDI clinical response |  | Day 12 | 
| Microbiological response of C. difficile total viable count, spore count, microbiological eradication and negative CDI toxin assay |  | Day 5 and Day 10 | 
| Stool concentrations of fidaxomicin and its metabolite OP-1118 |  | Day 1, Day 5 and Day 10 | 
| Length of hospital stay, readmissions and resource utilization |  | up to Day 180 | 
| Safety as assessed by incidence and severity of adverse events |  | up to Day 180 | 
| Health related quality of life as assessed by short IBDQ score | Inflammatory Bowel Disease Questionnaire (IBDQ) | Day 10, Day 26, Day 40, Day 90 and Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP2819, PAR-101, OPT-80, Inflammatory Bowel Disease (IBD), Clostridium difficile Infection (CDI), fidaxomicin, Dificlir