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

Inflammatory Bowel Disease (IBD) Clinical Trial

— PROFILE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02437591
• Other study ID #: 2819-MA-1003
• Secondary ID: 2014-003002-32
• Status: Completed
• Phase: Phase 4
• Start date: August 13, 2015
• Est. completion date: October 24, 2016

Study information

• Verified date: August 2018
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: October 24, 2016
• Est. primary completion date: May 12, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Clostridium Difficile Infection (CDI)
• Communicable Diseases
• Infection
• Inflammatory Bowel Disease (IBD)
• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Drug:
• fidaxomicin
oral

Locations

Country	Name	City	State
Austria	Site AT43001	Graz
France	Site FR33002	Clichy
France	Site FR33001	Paris
Greece	Site GR30004	Athens
Italy	Site IT39003	Padova
Italy	Site IT39001	Roma
Poland	Site PL48003	Warsaw
Poland	Site PL48002	Warszawa
Russian Federation	Site RU70002	Moscow
Russian Federation	Site RU70003	Moscow
Russian Federation	Site RU70001	Saint Petersburg
United Kingdom	Site GB44002	London

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe Ltd.

Countries where clinical trial is conducted

Austria,  France,  Greece,  Italy,  Poland,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameter of fidaxomicin: Maximum plasma concentration (Cmax)		Day 1, Day 5 and Day 10
Primary	Pharmacokinetic parameter of OP-1118: Maximum plasma concentration (Cmax)		Day 1, Day 5 and Day 10
Primary	Pharmacokinetic parameter of fidaxomicin: Area under the curve from 0 to 12 hrs (AUC12)		Day 1
Primary	Pharmacokinetic parameter of OP-1118: Area under the curve from 0 to 12 hrs (AUC12)		Day 1
Primary	Pharmacokinetic parameter of fidaxomicin and OP-1118: Metabolite to Parent Ratio (MPR)		Day 1
Primary	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
Primary	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
Primary	Pharmacokinetic parameter of fidaxomicin: The time after dosing when Cmax occurs (tmax)		Day 1, Day 5 and Day 10
Primary	Pharmacokinetic parameter of OP-1118: The time after dosing when Cmax occurs (tmax)		Day 1, Day 5 and Day 10
Primary	Pharmacokinetic parameter of fidaxomicin: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)		Day 5 and Day 10
Primary	Pharmacokinetic parameter of OP-1118: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)		Day 5 and Day 10
Primary	Pharmacokinetic parameter of fidaxomicin: Concentration immediately prior to dosing at multiple dosing (Ctrough)		Day 5 and Day 10
Primary	Pharmacokinetic parameter of OP-1118: Concentration immediately prior to dosing at multiple dosing (Ctrough)		Day 5 and Day 10
Secondary	CDI clinical response		Day 12
Secondary	Microbiological response of C. difficile total viable count, spore count, microbiological eradication and negative CDI toxin assay		Day 5 and Day 10
Secondary	Stool concentrations of fidaxomicin and its metabolite OP-1118		Day 1, Day 5 and Day 10
Secondary	Length of hospital stay, readmissions and resource utilization		up to Day 180
Secondary	Safety as assessed by incidence and severity of adverse events		up to Day 180
Secondary	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

External Links

•   Link to results on the Astellas Clinical Study Results website