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

NCT02437591 | Completed Phase 4 DMC

• 2 other identifiers: 2819-MA-10032014-003002-32
• Study Type: interventional
• Target: 25
• Locations: 7 countries
• Sites: 12

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.

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

Outcome Measures

Primary Outcomes (13)

• 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 Outcomes (6)

• 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

Study Arms (1)

fidaxomicin

EXPERIMENTAL

tablet twice daily

Drug: fidaxomicin

Interventions

fidaxomicin DRUG

oral

Also known as: PAR-101, OPT-80, Dificlir, ASP2819

fidaxomicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Europe Ltd.: lead

Study Sites (12)

Site AT43001

Graz, 8036, Austria

Location

Site FR33002

Clichy, 92110, France

Location

Site FR33001

Paris, 75012, France

Location

Site GR30004

Athens, 11527, Greece

Location

Site IT39003

Padua, 35128, Italy

Location

Site IT39001

Roma, Italy

Location

Site PL48002

Warsaw, 02-507, Poland

Location

Site PL48003

Warsaw, 02-781, Poland

Location

Site RU70003

Moscow, 119435, Russia

Location

Site RU70002

Moscow, 129110, Russia

Location

Site RU70001

Saint Petersburg, 196247, Russia

Location

Site GB44002

London, E11 1NR, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30260412 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Clostridium Infections

Interventions

Fidaxomicin; OPT 80

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Polyketides; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Medical Monitor

  Astellas Pharma Europe Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 7, 2015
• Study Start: August 13, 2015
• Primary Completion: May 12, 2016
• Study Completion: October 24, 2016
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); GR (1); AU (1); IT (2); PL (2); FR (2); RU (3)