E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of enterocolitis caused by Clostridium difficile |
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E.1.1.1 | Medical condition in easily understood language |
Diarrhea caused with bacteria named Clostridium Difficile |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012734 |
E.1.2 | Term | Diarrhea, Clostridium difficile |
E.1.2 | System Organ Class | 100000004862 |
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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 this study is to investigate the clinical response to fidaxomicin oral suspension or tablets and vancomycin oral liquid or capsules of pediatric subjects with Clostridium difficile-associated diarrhea (CDAD) from birth to < 18 years of age. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to investigate the recurrence/sustained clinical response to and safety of fidaxomicin and vancomycin in pediatric subjects with Clostridium difficile-associated diarrhea (CDAD) from birth to < 18 years of age, as well as acceptance of the fidaxomicin oral suspension formulation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent/ assent ( if applicable) and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Male and female subjects from birth to < 18 years of age.
3.Subject is diagnosed with CDAD according to local diagnostic criteria. As a minimum there must be positive detection, within 72 hours prior to randomization, of either toxin A and/or toxin B in stool or positive detection of toxigenic C. difficile in stool and:
a.Subject from birth to < 2 years of age: watery diarrhea in the 24 hours prior to screening.
b.Subject ≥ 2 years to < 18 years: > 3 unformed bowel movements in the 24 hours prior to screening.
4. For subjects < 5 years: Negative rotavirus test.
5. Female subject of childbearing potential:
a. must have a negative urine pregnancy test at Screening, and
b. must abstain from sexual activity for the duration of the study, or
c. must use two forms of birth control* (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days after the final study drug administration.
6. Female subject must not be breastfeeding at Screening or during the study period, and for 28 days after the final study drug administration.
7. Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.
8. Subject agrees not to participate in another interventional study while in the study (with the exception of studies as described in exclusion criteria 6). |
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E.4 | Principal exclusion criteria |
1. Concurrent use of metronidazole, oral vancomycin or any other antibiotic treatments for CDAD. If the investigator feels the clinical imperative is to begin treatment before knowing the laboratory result for toxigenic C. difficile, up to four doses but no more than 24 hours of treatment with metronidazole, oral vancomycin or any other effective treatment for CDAD are allowed.
2. Subject has pseudomembranous colitis, fulminant colitis, toxic megacolon or ileus.
3. Subject has a history of inflammatory bowel disease (e.g., ulcerative colitis or Crohn‟s disease etc.).
4. Subject has diarrhea caused by an agent other than C. difficile (e.g. infections, infestations, drugs etc.).
5. Subject has known hypersensitivity to fidaxomicin, vancomycin or their excipients or to teicoplanin.
6. Subject has received an investigational therapy within 28 days, prior to Screening, with the exception of studies with primary treatment for cancer without novel Investigational Medicinal
Product (IMP) and which do not affect the assessment of diarrhea.
7. Subject has a condition which, in the investigator‟s opinion, makes the subject unsuitable for study participation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Confirmed clinical response based on the assessment by the investigator at EOT+2 days TC/visit |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy
- Sustained clinical response at the EOS (EOT visit+30 days)
- Sustained clinical response 14 days after Confirmation Clinical Response TC/visit (EOT visit+16 days)
- Time to resolution of diarrhea (TTROD)
- Recurrence of CDAD during or at the end of the Follow-up period
- Time to recurrence during or at the end of the Follow-up period
Safety:
The safety evaluation will include adverse events, clinical laboratory tests (hematology, biochemistry and urinalysis), vital signs and ECGs.
Drug concentration measurement:
•Plasma concentrations of fidaxomicin and its main metabolite (OP-1118) within 30 minutes pre-dose and 1 to 5 hours post-dose taken between Day 5 and 10, inclusive.
•Fecal concentration of fidaxomicin and its main metabolite (OP-1118) within 24 hours of a dose taken between Day 5 and 10, inclusive.
Palatability:
Acceptance of formulation at first administration of study drug and at Day 7 (± 1 day) in all subjects receiving fidaxomicin oral suspension or vancomycin oral liquid.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy
- EOS (EOT visit+30 days)
- EOT visit+16 days
- Throughout the study including follow up period
Safety
- daily assesments: -2,1,2-4,5-10,10, EOT+2, EOT+9, 16&23, EOT+30 |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Belgium |
Canada |
France |
Germany |
Hungary |
Italy |
Poland |
Romania |
Slovakia |
Spain |
United States |
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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
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |