E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of enterocolitis caused by Clostridium difficile |
Tratamiento de la enterocolitis causada por Clostridium difficile |
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E.1.1.1 | Medical condition in easily understood language |
Diarrhea caused with bacteria named Clostridium Difficile |
Diarrea causada por la bacteria 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) aged ? 6 months to < 18 years. |
El objetivo principal de este estudio es evaluar la respuesta clínica de sujetos pediátricos de ? 6 meses a < 18 años con diarrea asociada a Clostridium difficile (DACD) a la fidaxomicina en suspensión oral o comprimidos, y a la vancomicina en solución oral o cápsulas. |
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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) aged ? 6 months to < 18 years, as well as acceptance of the fidaxomicin oral suspension formulation. |
Los objetivos secundarios de este estudio son evaluar la reaparición / respuesta clínica sostenida y la seguridad de fidaxomicina y vancomicina en sujetos pediátricos de ? 6 meses a < 18 años con diarrea asociada a Clostridium difficile (DACD), así como la aceptación de la formulación de fidaxomicina en suspensión oral. |
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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 aged ? 6 months to < 18 years. 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 ? 6 months to < 2 years: 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). |
1. Deberá obtenerse el asentimiento (si procede) o el consentimiento informado escrito aprobado por el Comité Ético de la Investigación Clínica (CEIC) y la aceptación de la declaración de privacidad de acuerdo con las normativas nacionales (p. ej., autorización HIPAA en los centros estadounidenses) del sujeto o su representante legal antes de realizar cualquier procedimiento relacionado con el estudio (incluida la retirada de los medicamentos prohibidos, si procede). 2. Sujetos de ambos sexos de ? 6 meses a < 18 años de edad. 3. Sujetos con diagnóstico de DACD según los criterios de diagnóstico locales. Como mínimo, debe haber detección positiva, en las 72 horas previas a la aleatorización, de toxina A y/o toxina B en las heces, o detección positiva de C. difficile toxinógeno en las heces, y: a. Sujetos de ? 6 meses a < 2 años de edad: diarrea líquida en las 24 horas previas a la selección. b. Sujetos de ? 2 años a < 18 años de edad: ? 3 deposiciones informes en las 24 horas previas a la selección. 4. Para los sujetos menores de 5 años: prueba de rotavirus negativa. 5. Mujeres en edad fértil: a. Deberán tener un resultado negativo en una prueba de embarazo en orina realizada en la selección, y b. Deberán abstenerse de tener relaciones sexuales mientras dure el estudio, o c. Deberán utilizar dos métodos anticonceptivos* (al menos uno de los cuáles debe ser un método de barrera) desde la selección y durante todo el periodo del estudio, y durante 28 días después de la última administración del fármaco del estudio. 6. Las mujeres no deben estar amamantando en la selección ni durante el estudio, así como durante 28 días después de la última administración del fármaco del estudio. 7. Las mujeres no deben donar óvulos desde la selección y durante todo el estudio, así como durante 28 días después de la última administración del fármaco del estudio. 8. El sujeto acepta no participar en otros estudios intervencionistas mientras participe en este estudio (con excepción de los estudios descritos en el criterio de exclusión 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. |
Exclusión: 1. Uso concomitante de metronidazol, vancomicina oral o cualquier otro antibiótico para la DACD. Si el investigador cree que es clínicamente importante iniciar el tratamiento antes de contar con el resultado de laboratorio de C. difficile toxinógeno, se permiten hasta cuatro dosis y no más de 24 horas de tratamiento con metronidazol, vancomicina oral o cualquier otro tratamiento eficaz para la DACD. 2. El sujeto tiene colitis seudomembranosa, colitis fulminante, megacolon tóxico o íleo.? 3. El sujeto tiene antecedentes de enfermedad intestinal inflamatoria (p. ej., colitis ulcerosa o enfermedad de Crohn, etc.). 4. El sujeto tiene diarrea causada por un agente que no sea C. difficile (p. ej., infecciones, infestaciones, fármacos, etc.). 5. El sujeto tiene hipersensibilidad conocida a la fidaxomicina, la vancomicina o sus excipientes, o a la teicoplanina. 6. El sujeto ha recibido un tratamiento en fase de investigación en los 28 días anteriores a la selección, con excepción de los estudios de tratamiento primario para el cáncer sin medicamentos nuevos en fase de investigación (PEI), y que no afecte a la evaluación de la diarrea. 7. El sujeto tiene una afección que, en opinión del investigador, hace que no sea apto para participar en el estudio. |
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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 |
Respuesta clínica confirmada basada en la evaluación realizada por el investigador (al FDT+2 días) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at EOT+2 days TC/visit |
al FDT+2 días |
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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. |
Eficacia - Respuesta clínica sostenida al FDE (FDT + 30 días) - Respuesta clínica sostenida 14 días después de la confirmación de la respuesta clínica (FDT +16 días) - Tiempo hasta la resolución de la diarrea (TRD) - Reaparición de DACD durante o al final del periodo de seguimiento - Tiempo hasta la recaída durante o al final del periodo de seguimiento Seguridad: La evaluación de seguridad incluirá los acontecimientos adversos, los análisis clínicos (hematología, bioquímica y análisis de orina), las constantes vitales y el ECG. |
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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 |
Eficacia FDE (visita FDT + 30 días) FDE (visita FDT + 16 días) Durante o al final del periodo de seguimiento Seguridad Evaluaciones diarias: -2,1,2-4,5-10,10, FDE+2, FDE+9, 16&23, FDE+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 | 5 |
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 |
Croatia |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Latvia |
Lithuania |
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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LVLS |
Última visita del último paciente |
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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 |