Clinical trial NCT02437591: Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Inflammatory Bowel Disease (IBD)
Clostridium Difficile Infection (CDI)
Keywords: ASP2819
PAR-101
OPT-80
Inflammatory Bowel Disease (IBD)
Clostridium difficile Infection (CDI)
fidaxomicin
Dificlir
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2015-05-07
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Pharmacokinetic parameter of fidaxomicin: Maximum plasma concentration (Cmax)
timeFrame: Day 1, Day 5 and Day 10
measure: Pharmacokinetic parameter of OP-1118: Maximum plasma concentration (Cmax)
timeFrame: Day 1, Day 5 and Day 10
measure: Pharmacokinetic parameter of fidaxomicin: Area under the curve from 0 to 12 hrs (AUC12)
timeFrame: Day 1
measure: Pharmacokinetic parameter of OP-1118: Area under the curve from 0 to 12 hrs (AUC12)
timeFrame: Day 1
measure: Pharmacokinetic parameter of fidaxomicin and OP-1118: Metabolite to Parent Ratio (MPR)
timeFrame: Day 1
measure: Pharmacokinetic parameter of fidaxomicin: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau)
timeFrame: Day 5 and Day 10
measure: 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)
timeFrame: Day 5 and Day 10
measure: Pharmacokinetic parameter of fidaxomicin: The time after dosing when Cmax occurs (tmax)
timeFrame: Day 1, Day 5 and Day 10
measure: Pharmacokinetic parameter of OP-1118: The time after dosing when Cmax occurs (tmax)
timeFrame: Day 1, Day 5 and Day 10
measure: Pharmacokinetic parameter of fidaxomicin: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)
timeFrame: Day 5 and Day 10
measure: Pharmacokinetic parameter of OP-1118: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)
timeFrame: Day 5 and Day 10
measure: Pharmacokinetic parameter of fidaxomicin: Concentration immediately prior to dosing at multiple dosing (Ctrough)
timeFrame: Day 5 and Day 10
measure: Pharmacokinetic parameter of OP-1118: Concentration immediately prior to dosing at multiple dosing (Ctrough)
timeFrame: Day 5 and Day 10
Secondary outcomes:
measure: CDI clinical response
timeFrame: Day 12
measure: Microbiological response of C. difficile total viable count, spore count, microbiological eradication and negative CDI toxin assay
timeFrame: Day 5 and Day 10
measure: Stool concentrations of fidaxomicin and its metabolite OP-1118
timeFrame: Day 1, Day 5 and Day 10
measure: Length of hospital stay, readmissions and resource utilization
timeFrame: up to Day 180
measure: Safety as assessed by incidence and severity of adverse events
timeFrame: up to Day 180
measure: Health related quality of life as assessed by short IBDQ score
timeFrame: Day 10, Day 26, Day 40, Day 90 and Day 180
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Site AT43001
city: Clichy
country: France
facility: Site FR33002
city: Paris
country: France
facility: Site FR33001
city: Athens
country: Greece
facility: Site GR30004
city: Padova
country: Italy
facility: Site IT39003
city: Roma
country: Italy
facility: Site IT39001
city: Warsaw
country: Poland
facility: Site PL48003
city: Warszawa
country: Poland
facility: Site PL48002
city: Moscow
country: Russian Federation
facility: Site RU70003
city: Moscow
country: Russian Federation
facility: Site RU70002
city: Saint Petersburg
country: Russian Federation
facility: Site RU70001
city: London
country: United Kingdom
facility: Site GB44002
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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.