Clinical Trial Results:
Open Label Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects with Clostridium Difficile Infection (CDI)
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Summary
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EudraCT number |
2014-003002-32 |
Trial protocol |
CZ DE AT GR PL IT |
Global end of trial date |
24 Oct 2016
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Results information
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Results version number |
v2(current) |
This version publication date |
26 Dec 2020
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First version publication date |
28 Oct 2017
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2819-MA-1003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02437591 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Astellas Pharma Europe Ltd.
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Sponsor organisation address |
2000 Hillswood Drive, Chertsey, United Kingdom, KT16 0RS
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Public contact |
Clinical Trial Disclosure, Astellas Pharma Europe Ltd., astellas.resultsdisclosure@astellas.com
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Scientific contact |
Clinical Trial Disclosure, Astellas Pharma Europe Ltd., astellas.resultsdisclosure@astellas.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Oct 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Oct 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the trial was to investigate the plasma pharmacokinetics of fidaxomicin and its primary metabolite OP-1118, in participants with inflammatory bowel disease (IBD) and clostridium difficile infection (CDI).
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Protection of trial subjects |
This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Aug 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Greece: 3
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Poland: 9
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Country: Number of subjects enrolled |
Russian Federation: 7
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Country: Number of subjects enrolled |
Austria: 1
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Country: Number of subjects enrolled |
United Kingdom: 1
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Worldwide total number of subjects |
25
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EEA total number of subjects |
18
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
22
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled at 28 clinical sites across 9 European countries and regions. | ||||||||||||
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Pre-assignment
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Screening details |
Male or female participants of at least 18 years of age with confirmed diagnosis or history of IBD for at least 3 months and a positive local standard CDI test for the presence of C. difficile. A CDI stool test had to be confirmed positive within 48 hours prior to enrollment. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (Treatment & Follow Up) (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Fidaxomicin | ||||||||||||
Arm description |
Participants received 200 mg of fidaxomicin from day 1 to day 10, twice daily. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Fidaxomicin
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Investigational medicinal product code |
OPT-80, PAR-101, ASP2819
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Other name |
Dificlir TM, Dificid, Difimicin
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 200 mg of fidaxomicin orally, twice a day (every 12 hours) starting on day 1 for 10 treatment days.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study (Treatment & Follow Up)
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Reporting group description |
Treatment Period & Follow Up Period | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
IBD type - Crohn’s Disease
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants with Crohn’s Disease with positive CDI test for the presence of C. difficile who received 200 mg of fidaxomicin from day 1 to day 10, twice daily.
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Subject analysis set title |
IBD type - Ulcerative Colitis
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants with Ulcerative Colitis with positive CDI test for the presence of C. difficile who received 200 mg of fidaxomicin from day 1 to day 10, twice daily.
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Subject analysis set title |
Responders
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The analysis population was the modified full analysis set (mFAS), which consisted of all participants with confirmed CDI who received at least 1 dose of study treatment and had a valid assessment of TOC. Responders are participants assessed as cured from CDI at Day 12.
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Subject analysis set title |
Non-Responders
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The analysis population was the mFAS.
Non-Responders are participants assessed as not cured from CDI at Day 12.
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End points reporting groups
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Reporting group title |
Fidaxomicin
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Reporting group description |
Participants received 200 mg of fidaxomicin from day 1 to day 10, twice daily. | ||
Subject analysis set title |
IBD type - Crohn’s Disease
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants with Crohn’s Disease with positive CDI test for the presence of C. difficile who received 200 mg of fidaxomicin from day 1 to day 10, twice daily.
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Subject analysis set title |
IBD type - Ulcerative Colitis
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants with Ulcerative Colitis with positive CDI test for the presence of C. difficile who received 200 mg of fidaxomicin from day 1 to day 10, twice daily.
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Subject analysis set title |
Responders
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The analysis population was the modified full analysis set (mFAS), which consisted of all participants with confirmed CDI who received at least 1 dose of study treatment and had a valid assessment of TOC. Responders are participants assessed as cured from CDI at Day 12.
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Subject analysis set title |
Non-Responders
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The analysis population was the mFAS.
Non-Responders are participants assessed as not cured from CDI at Day 12.
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End point title |
Maximum Plasma Concentration (Cmax) for Fidaxomicin [1] | ||||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients), which consisted of all participants from the subset of the safety analysis set (SAF). The safety analysis set (SAF) consisted of all participants who received at least 1 dose of study drug. The PKAS population contained at least 1 blood plasma measurement of fidaxomicin and its metabolite OP-1118, regardless of whether the value of the measurement was above or below lower limit of quantification and whether the participant had a full pharmacokinetic sampling profile or a limited pharmacokinetic sampling profile. For participants with limited PK sampling, Cmax on Days 5 and 10 was estimated by value from scheduled time window for tmax (2 hours ± 30 minutes). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
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End point type |
Primary
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End point timeframe |
Day 1, Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Maximum Plasma Concentration (Cmax) for OP-1118 [2] | ||||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). For participants with limited PK sampling, Cmax on Days 5 and 10 was estimated by value from scheduled time window for tmax (2 hours ± 30 minutes). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
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End point type |
Primary
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End point timeframe |
Day 1, Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Area Under the Curve from 0 to 12 hrs (AUC12) for Fidaxomicin [3] | ||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax).
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End point type |
Primary
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End point timeframe |
Day 1 (Predose to 12 hours postdose)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Area Under the Curve from 0 to 12 hrs (AUC12) for OP-1118 [4] | ||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax).
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End point type |
Primary
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End point timeframe |
Day 1 (Predose to 12 hours postdose)
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time of Maximum Concentration (tmax) for Fidaxomicin [5] | ||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
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End point type |
Primary
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End point timeframe |
Day 1, Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Time of Maximum Concentration (tmax) for OP-1118 [6] | ||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
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End point type |
Primary
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End point timeframe |
Day 1, Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Metabolite-to-Parent Ratio (MPR) for OP-1118 [7] | ||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
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End point type |
Primary
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End point timeframe |
Day 1, Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Area Under the Concentration Time Curve From the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) for Fidaxomicin [8] | ||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
|
||||||||||||
| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Area Under the Concentration Time Curve From the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) for OP-1118 [9] | ||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
|
||||||||||||
| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) for Fidaxomicin [10] | ||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
|
||||||||||||
| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) for OP-1118 [11] | ||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
|
||||||||||||
| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||
End point title |
Apparent Total Systemic Clearance After Single or Multiple Extra-Vascular Dosing (CL/F) for Fidaxomicin [12] | ||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Day 1, Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
|
||||||||||||||
| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
|||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Apparent Total Systemic Clearance After Single or Multiple Extra-Vascular Dosing (CL/F) for OP-1118 [13] | ||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). N represents number of participants with the available data.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Day 1, Day 5 and Day 10 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose)
|
||||||||||||||
| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis for this endpoint was not completed. |
|||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Stool Concentrations of Fidaxomicin Throughout Fidaxomicin Treatment on Day 1, Day 5, Day 10 and at Any Unscheduled Failure Visit | ||||||||||||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Concentrations below the limit of quantification (10 ng/mL of diluted fecal homogenate or about 2 mcg/g fecal concentrations) were set to zero. Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). Day 1 as per protocol data excludes fecal samples taken less than 12-hours after the first dose. N represents number of participants with the available data.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Day 1, Day 5 and Day 10
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Stool Concentrations of Metabolite OP-1118 Throughout Fidaxomicin Treatment on Day 1, Day 5, Day 10 and at Any Unscheduled Failure Visit | ||||||||||||||||||||||||
End point description |
The analysis population was the pharmacokinetic analysis set (PKAS All Patients). Concentrations below the limit of quantification (10 ng/mL of diluted fecal homogenate or about 2 mcg/g fecal concentrations) were set to zero. Sampling for participants with reduced PK profile was completed on Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 hours postdose) and Day 5 & 10 (Predose and tmax). Day 1 as per protocol data excludes fecal samples taken less than 12-hours after the first dose. N represents number of participants with the available data.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Day 1, Day 5 and Day 10
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants with Clinical Response of CDI at Day 12 Test of Cure (TOC) after End of Treatment (EoT) | ||||||||||||||||
End point description |
The analysis population was the modified full analysis set (mFAS). The CDI clinical response (ToC) was based on the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Treatment response was present when either stool frequency decreased or stool consistency improved and parameters of disease severity (clinical, laboratory, radiological) improved and there were no new signs of severe disease developed. In all other cases, treatment was considered a failure. Treatment response was observed daily and evaluated after at least three days, assuming that the participant was not worsening on treatment.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 12 (48-72 hours after EoT)
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||
End point title |
Health Economic and Resource Variables by CDI Response at ToC on Day 12 – Overall Length of Hospital Stay | ||||||||||||||
End point description |
The analysis population was modified full analysis set (mFAS). Health economic and resource variables were stratified by clinical response of CDI at ToC on day 12 (yes/no/total). Responders/nonresponders were participants assessed as cured/not cured for clinical response for CDI at day 12. N represents number of participants with the available data.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Day 1 to Day 180
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Health Economic and Resource Variables by CDI Response at ToC on Day 12 – Length of Stay on Isolated Ward | ||||||||||||||
End point description |
The analysis population was modified full analysis set (mFAS). Health economic and resource variables were stratified by clinical response of CDI at ToC on day 12 (yes/no/total). Responders/nonresponders were participants assessed as cured/not cured for clinical response for CDI at day 12. N represents number of participants with the available data.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Day 1 to Day 180
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Health Economic and Resource Variables by CDI Response at ToC on Day 12 – Length of Hospital Stay With Reason CDI Recurrence | ||||||||||||||
End point description |
The analysis population was modified full analysis set (mFAS). Health economic and resource variables were stratified by clinical response of CDI at ToC on day 12 (yes/no/total). Responders/nonresponders were participants assessed as cured/not cured for clinical response for CDI at day 12. N represents number of participants with the available data.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Day 1 to Day 180
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Health Economic and Resource Variables by CDI Response at ToC on Day 12 – Hospital Admissions | ||||||||||||||
End point description |
The analysis population was modified full analysis set (mFAS). Health economic and resource variables were stratified by clinical response of CDI at ToC on day 12 (yes/no/total). Responders/nonresponders were participants assessed as cured/not cured for clinical response for CDI at day 12. N represents number of participants with the available data.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Day 1 to Day 180
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||
End point title |
Health-Related Quality of Life (HRQoL) as Measured by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Score | ||||||||||||||||||
End point description |
The HRQoL total score results are based on the SIBDQ that consisted of 10 items covering 4 dimensions and 7 levels: Bowel dimension, Systemic dimension, Emotional dimension and the Social dimension. The Short IBDQ questionnaire consisted of 10 questions, each was graded on a scale from 1 (worst case) to 7. All scores were averaged by dividing each score by its number of items so that all score ranges are from 1 to 7, with one being poor and 7 optimum health related quality of life. The analysis population was the modified full analysis set (mFAS). N represents number of participants with the available data.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 10, Day 26, Day 40,Day 90 and Day 180 (EOS)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) up to 30 days after End of Treatment (EOT) | ||||||||||||||||||||||||
End point description |
A TEAE was defined as an AE starting, or an existing condition that worsened, after first drug intake and until 30 days after the EoT visit on day 10. The analysis population was safety analysis set (SAF) and it consisted of all participants who received at least 1 dose of study drug.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From first dose of study drug up to 30 days after the EOT visit (Day 10)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Change from baseline in magnitude of C. difficile Total Viable Count at Day 5 and Day 10 | ||||||||||||||||||
End point description |
Microbiological response in terms of C. difficile total viable count was analyzed by presenting the frequency and percentage of participants with microbial eradication at visit day 5 and 10. Viable count collected between baseline and TOC (Day 12) was summarized by visit with descriptive statistics for continuous variables showing absolute measurements and change from baseline. The analysis population was the mFAS.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 5 and Day 10
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Change from baseline in magnitude of C. difficile Spore Count at Day 5 and Day 10 | ||||||||||||||||||
End point description |
Microbiological response was evaluated in terms of magnitude of C.difficile total spore count at Days 5 and 10. Spore count collected between baseline and TOC (Day 12) was summarized by visit with descriptive statistics for continuous variables showing absolute measurements and change from baseline. The analysis population was the mFAS.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 5 and Day 10
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants with Bacterial Eradication at Day 5 and Day 10 | ||||||||||||
End point description |
Bacterial Eradication is defined as having both total viable count and spore count below the lower limit of quantification (BLQ). Bacterial response in terms of C. difficile was analyzed by presenting the frequency and percentage of participants with bacterial eradication at Visit day 5 and day 10. The analysis population was the mFAS. N is the number of participants with available data at each time point. For Day 5, there were 14 responders and for Day 10, there were 19 responders.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 5 and Day 10
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Negative C. difficile Toxin Assay | ||||||||||||||||||||||||||||||
End point description |
C. difficile Toxin Assay is a conventional microbiological assay to identify C. difficile in clinical laboratory samples of infected participants. Results from CDI toxin assay in stool specimens were summarized, showing the number and percentage of participants in each result category. The analysis population was the mFAS. N is the number of participants with available data at each time point. The total number of responders per day were as follows:
Day 5 (17 of 17), Day 10 (19 of 19), Day 26 (14 of 19), Day 40 (13 of 15), Day 90 (14 of 15), and Day 180 (15 of 15). The total number of non-responders per day were as follows: Day 5 (5 of 5), Day 10 (5 of 5), Day 26 (4 of 4), Day 40 (5 of 5), Day 90 (5 of 5), and Day 180 (4 of 4).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Days 5, 10, 26, 40, 90, and 180 (End of Study)
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first dose of study drug up to 7 days after EOS (up to 187)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
An adverse events (AE) was defined as any untoward medical occurrence in a participants administered a study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment. All participants remained in the study until end of study (EoS) visit 8 (day 180) for safety assessments.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fidaxomicin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received 200 mg of fidaxomicin orally, twice a day (every 12 hours) on day 1 for 10 treatment days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
19 Aug 2015 |
-The phase of study was amended from phase 4 to phase 3b/4. As fidaxomicin was not an approved drug within the Russian Federation, this study was to be regarded as a phase 3b study.
-To maximize the probability of enrolling the required number of participants within the stipulated enrollment period, 3 sites in the Russian Federation were added to the study.
-The time point changed from 12 to 10 hours postdose of fidaxomicin and acceptable time window (changed from within 24 hours of first dose to not earlier than 12 hours) for the last pharmacokinetic sampling was updated to introduce some flexibility to assist the logistical challenges faced by the clinical sites.
-In the protocol text it was clarified when to take stool samples.
-In the protocol text it was clarified that the review of pharmacokinetic data was ongoing throughout the study.
-In the protocol text it was clarified that the enrollment was interrupted after the first 3 patients.
-Definitions of activity of IBD were updated in the inclusion criteria. New recommendations for ‘active IBD’ have been discussed among authorities and IBD specialists and will assist with the analyses of efficacy, as discussed with the protocol
Steering Committee.
-As some medication on the list had to be used in case of failure and/or recurrence of CDI, the protocol terminology was amended from ‘prohibited medication’ to ‘medication to be avoided’.
-Independent’ was added in the text before Data Monitoring Committee (DMC), to clarify that the external DMC was independent.
-The information regarding the stool sample taken for enrollment was updated. As it could take time to retrieve the results from CDI testing, the wording in the text was changed to ‘the time of confirmation of CDI diagnosis’ rather than ‘the time of sample taken’ so participantscould be enrolled within 48 hours after receiving the diagnosis of CDI. |
||
19 Aug 2015 |
-In the protocol text it was clarified when screening samples for safety laboratory assessment were to be taken.
-The SmPC was added as reference safety information for AEs for countries where fidaxomicin was an approved drug.
-For the AEs of special interest, the ranges for hepatic laboratory abnormalities were updated as clarified by the global pharmacovigilance department.
-The information regarding the collection of treatment-emergent adverse events (TEAEs) was updated. As this study was continuous for a long period after the stop of study drug, a distinction was made between ‘TEAEs’ and ‘other AEs’.
-As endoscopic findings were not part of the Mayo Score, the information regarding endoscopic findings was removed and the summary of score was updated.
-The CDI clinical assessment and severity score was deleted from visit 4. This assessment could not be performed as this visit was conducted over the telephone.
-To improve the evaluation of outcomes of IBD during the study, definitions were added for the response and flare of both ‘ulcerative colitis’ and ‘Crohn’s disease’.
-As requested by the IEC in the UK, the number of mucosal samples taken during the study was maximized to 4.
-Contact details of sponsor’s personnel were updated to reflect the change of role of the medical expert and changes to European and regional study management. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was on hold after first 3 participants PK results were examined to ensure maximum plasma concentrations were not high and to minimize the safety risks. The Microbiological Response endpoint data are available at this time. | |||
