E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with Clostridium difficile infection who are receiving immunosuppressive therapy. |
|
E.1.1.1 | Medical condition in easily understood language |
Adult patients with an infection of Clostridium difficile who are using medicinal products that suppress the immune system. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061043 |
E.1.2 | Term | Clostridial infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to demonstrate superiority of fidaxomicin versus vancomycin for the sustained clinical cure of Clostridium difficile Infection (CDI) in adult patients receiving immunosuppressive therapy. Sustained clinical cure is defined as clinical cure without CDI recurrence within 14 days from the assessment of clinical cure [Test of Cure (TOC).] |
|
E.2.2 | Secondary objectives of the trial |
The key secondary objective of this study is - To demonstrate superiority of fidaxomicin versus vancomycin for clinical cure of CDI at TOC on Day 12 Further Secondary objectives of this study are - To compare the rates of clinical cure of CDI at TOC on Day 12 and of sustained clinical cure of CDI at Day 40 after treatment with fidaxomicin or vancomycin - To compare the recurrence rate of CDI after treatment with fidaxomicin or vancomycin - To compare the time to resolution of diarrhea on treatment with fidaxomicin or vancomycin |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject is eligible for the study if all of the following apply: 1. Subject is 18 years of age or over.
2. CDI is confirmed by clinical symptoms and rapid CDI test
3. Subject has not been treated with medication or other therapy for CDI within the last 10 days.
4. Subject is: - receiving immunosuppressive therapy (chemotherapy) for a hematological malignancy or is undergoing a stem cell transplant procedure (defined as the time period from the start of conditioning prior to transplant until 6 months after infusion of stem cells); or - receiving immunosuppressive therapy (chemotherapy) for a solid tumor malignancy or following solid organ transplantation; or - being treated with immunosuppressive and /or anti-TNF therapy for an auto-immune disease or related illness
5. Subject has signed written informed consent.
6. Any woman of childbearing potential requires negative serum or urine pregnancy test before entry to the study.
7. Male and female subjects that are sexually active must agree to practice effective birth control during the study and for 30 days after the end of the study. (An effective method of birth control is defined as those which result in a low failure rate (CPMP/ICH/286/95 modified) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner). |
|
E.4 | Principal exclusion criteria |
Subject will be excluded from participation in this study if any of the following apply:
1. The subject has experienced more than one previous episode of CDI within the 3 months prior to study inclusion.
2. Taking or requiring to be treated with prohibited medications
3. Unable to take oral study medication.
4. Female patients that are pregnant, intend to become pregnant or are breastfeeding.
5. History of ulcerative colitis or Crohn's disease.
6. History or diagnosis of toxic megacolon or pseudomembranous colitis.
7. Not willing to adhere to the provisions of treatment and procedures specified in the protocol.
8. Has been randomised into this study previously, has taken any investigational drug within 28 days 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.
9. Hypersensitivity to fidaxomicin or any of its components.
10. Hypersensitivity to vancomycin or any of its components.
11. Any clinical condition which, in the opinion of the investigator, would not allow safe completion of this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is the rate of sustained clinical cure 14 days after TOC (at Day 26). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Clinical cure of CDI at TOC on Day 12 - Sustained clinical cure of CDI at Day 40, defined as clinical cure at TOC with no recurrence within 28 days after TOC - Microbial eradication at TOC, for the population with positive culture at baseline - Time to resolution of diarrhea, as measured from first dose of study medication - Use of further CDI therapy required between EOT and TOC - Number of unformed stools recorded between EOT and TOC - Marked reduction (at least 50%) in the number of unformed stools at TOC compared to baseline - Recurrence of CDI after TOC (for subjects with clinical cure at TOC) - Time to recurrence of CDI (for subjects with clinical cure at TOC)
Other Variables: - Health Related Quality of Life: EQ5D - Descriptive assessment and visual analogue scale (VAS) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 40 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 40 |