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

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

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease (IBD); Clostridium Difficile Infection (CDI)
• Intervention / Treatment: Drug: fidaxomicin

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Site AT43001
• France
  • Clichy, France, 92110
    • Site FR33002
  • Paris, France, 75012
    • Site FR33001
• Greece
  • Athens, Greece, 11527
    • Site GR30004
• Italy
  • Padova, Italy, 35128
    • Site IT39003
  • Roma, Italy
    • Site IT39001
• Poland
  • Warsaw, Poland, 02-781
    • Site PL48003
  • Warszawa, Poland, 02-507
    • Site PL48002
• Russian Federation
  • Moscow, Russian Federation, 119435
    • Site RU70003
  • Moscow, Russian Federation, 129110
    • Site RU70002
  • Saint Petersburg, Russian Federation, 196247
    • Site RU70001
• United Kingdom
  • London, United Kingdom, E11 1NR
    • Site GB44002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fidaxomicin; tablet twice daily	Drug: fidaxomicin; oral; Other Names: ASP2819; Dificlir; PAR-101; OPT-80

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe Ltd.
• Investigators: Study Director: Medical Monitor, Astellas Pharma Europe Ltd.

Publications and helpful links

General Publications

• Hogenauer C, Mahida Y, Stallmach A, Marteau P, Rydzewska G, Ivashkin V, Gargalianos-Kakolyris P, Michon I, Adomakoh N, Georgopali A, Tretter R, Karas A, Reinisch W. Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: an open-label Phase IIIb/IV study (PROFILE). J Antimicrob Chemother. 2018 Dec 1;73(12):3430-3441. doi: 10.1093/jac/dky368.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2015
• Primary Completion (Actual): May 12, 2016
• Study Completion (Actual): October 24, 2016

Study Registration Dates

• First Submitted: May 5, 2015
• First Submitted That Met QC Criteria: May 5, 2015
• First Posted (Estimate): May 7, 2015

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: August 14, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Inflammatory Bowel Disease (IBD); ASP2819; PAR-101; OPT-80; Clostridium difficile Infection (CDI); fidaxomicin; Dificlir
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Inflammatory Bowel Diseases; Intestinal Diseases; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Fidaxomicin
• Other Study ID Numbers: 2819-MA-1003; 2014-003002-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No