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

Primary Purpose

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

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
fidaxomicin
Sponsored by
Astellas Pharma Europe Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammatory Bowel Disease (IBD) focused on measuring ASP2819, PAR-101, OPT-80, Inflammatory Bowel Disease (IBD), Clostridium difficile Infection (CDI), fidaxomicin, Dificlir

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Site AT43001
  • Site FR33002
  • Site FR33001
  • Site GR30004
  • Site IT39003
  • Site IT39001
  • Site PL48003
  • Site PL48002
  • Site RU70003
  • Site RU70002
  • Site RU70001
  • Site GB44002

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

fidaxomicin

Arm Description

tablet twice daily

Outcomes

Primary Outcome Measures

Pharmacokinetic parameter of fidaxomicin: Maximum plasma concentration (Cmax)
Pharmacokinetic parameter of OP-1118: Maximum plasma concentration (Cmax)
Pharmacokinetic parameter of fidaxomicin: Area under the curve from 0 to 12 hrs (AUC12)
Pharmacokinetic parameter of OP-1118: Area under the curve from 0 to 12 hrs (AUC12)
Pharmacokinetic parameter of fidaxomicin and OP-1118: Metabolite to Parent Ratio (MPR)
Pharmacokinetic parameter of fidaxomicin: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau)
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)
Pharmacokinetic parameter of fidaxomicin: The time after dosing when Cmax occurs (tmax)
Pharmacokinetic parameter of OP-1118: The time after dosing when Cmax occurs (tmax)
Pharmacokinetic parameter of fidaxomicin: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)
Pharmacokinetic parameter of OP-1118: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)
Pharmacokinetic parameter of fidaxomicin: Concentration immediately prior to dosing at multiple dosing (Ctrough)
Pharmacokinetic parameter of OP-1118: Concentration immediately prior to dosing at multiple dosing (Ctrough)

Secondary Outcome Measures

CDI clinical response
Microbiological response of C. difficile total viable count, spore count, microbiological eradication and negative CDI toxin assay
Stool concentrations of fidaxomicin and its metabolite OP-1118
Length of hospital stay, readmissions and resource utilization
Safety as assessed by incidence and severity of adverse events
Health related quality of life as assessed by short IBDQ score
Inflammatory Bowel Disease Questionnaire (IBDQ)

Full Information

First Posted
May 5, 2015
Last Updated
August 14, 2018
Sponsor
Astellas Pharma Europe Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02437591
Brief Title
Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
Acronym
PROFILE
Official Title
Open Label Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
August 13, 2015 (Actual)
Primary Completion Date
May 12, 2016 (Actual)
Study Completion Date
October 24, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Europe Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Bowel Disease (IBD), Clostridium Difficile Infection (CDI)
Keywords
ASP2819, PAR-101, OPT-80, Inflammatory Bowel Disease (IBD), Clostridium difficile Infection (CDI), fidaxomicin, Dificlir

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
fidaxomicin
Arm Type
Experimental
Arm Description
tablet twice daily
Intervention Type
Drug
Intervention Name(s)
fidaxomicin
Other Intervention Name(s)
PAR-101, OPT-80, Dificlir, ASP2819
Intervention Description
oral
Primary Outcome Measure Information:
Title
Pharmacokinetic parameter of fidaxomicin: Maximum plasma concentration (Cmax)
Time Frame
Day 1, Day 5 and Day 10
Title
Pharmacokinetic parameter of OP-1118: Maximum plasma concentration (Cmax)
Time Frame
Day 1, Day 5 and Day 10
Title
Pharmacokinetic parameter of fidaxomicin: Area under the curve from 0 to 12 hrs (AUC12)
Time Frame
Day 1
Title
Pharmacokinetic parameter of OP-1118: Area under the curve from 0 to 12 hrs (AUC12)
Time Frame
Day 1
Title
Pharmacokinetic parameter of fidaxomicin and OP-1118: Metabolite to Parent Ratio (MPR)
Time Frame
Day 1
Title
Pharmacokinetic parameter of fidaxomicin: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau)
Time Frame
Day 5 and Day 10
Title
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)
Time Frame
Day 5 and Day 10
Title
Pharmacokinetic parameter of fidaxomicin: The time after dosing when Cmax occurs (tmax)
Time Frame
Day 1, Day 5 and Day 10
Title
Pharmacokinetic parameter of OP-1118: The time after dosing when Cmax occurs (tmax)
Time Frame
Day 1, Day 5 and Day 10
Title
Pharmacokinetic parameter of fidaxomicin: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)
Time Frame
Day 5 and Day 10
Title
Pharmacokinetic parameter of OP-1118: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)
Time Frame
Day 5 and Day 10
Title
Pharmacokinetic parameter of fidaxomicin: Concentration immediately prior to dosing at multiple dosing (Ctrough)
Time Frame
Day 5 and Day 10
Title
Pharmacokinetic parameter of OP-1118: Concentration immediately prior to dosing at multiple dosing (Ctrough)
Time Frame
Day 5 and Day 10
Secondary Outcome Measure Information:
Title
CDI clinical response
Time Frame
Day 12
Title
Microbiological response of C. difficile total viable count, spore count, microbiological eradication and negative CDI toxin assay
Time Frame
Day 5 and Day 10
Title
Stool concentrations of fidaxomicin and its metabolite OP-1118
Time Frame
Day 1, Day 5 and Day 10
Title
Length of hospital stay, readmissions and resource utilization
Time Frame
up to Day 180
Title
Safety as assessed by incidence and severity of adverse events
Time Frame
up to Day 180
Title
Health related quality of life as assessed by short IBDQ score
Description
Inflammatory Bowel Disease Questionnaire (IBDQ)
Time Frame
Day 10, Day 26, Day 40, Day 90 and Day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Astellas Pharma Europe Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Site AT43001
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Site FR33002
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Site FR33001
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Site GR30004
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Site IT39003
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Site IT39001
City
Roma
Country
Italy
Facility Name
Site PL48003
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Site PL48002
City
Warszawa
ZIP/Postal Code
02-507
Country
Poland
Facility Name
Site RU70003
City
Moscow
ZIP/Postal Code
119435
Country
Russian Federation
Facility Name
Site RU70002
City
Moscow
ZIP/Postal Code
129110
Country
Russian Federation
Facility Name
Site RU70001
City
Saint Petersburg
ZIP/Postal Code
196247
Country
Russian Federation
Facility Name
Site GB44002
City
London
ZIP/Postal Code
E11 1NR
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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."
Citations:
PubMed Identifier
30260412
Citation
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.
Results Reference
derived
Links:
URL
https://astellasclinicalstudyresults.com/study.aspx?ID=227
Description
Link to results on the Astellas Clinical Study Results website

Learn more about this trial

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

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