E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clostridium difficile-associated diarrhea (CDAD) |
Clostridium difficile-asociado a diarrea (CDAD) |
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E.1.1.1 | Medical condition in easily understood language |
Intestinal infection due to Clostridium difficile |
Infección intestinal debida a 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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012734 |
E.1.2 | Term | Diarrhea, Clostridium difficile |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054236 |
E.1.2 | Term | Clostridium difficile infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022661 |
E.1.2 | Term | Intestinal infection due to clostridium difficile |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012748 |
E.1.2 | Term | Diarrhoea, Clostridium difficile |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 Part A is to determine the cadazolid dose in children from birth to < 18 years of age by investigating the safety, efficacy, and the systemic and fecal pharmacokinetics (PK). The primary objective of Part B is to assess the safety and efficacy of cadazolid in children from birth to < 18 years of age as compared with vancomycin. |
El objetivo principal de la Parte A es determinar la dosis de cadazolid en niños desde el nacimiento hasta < 18 años de edad mediante la investigación de la seguridad, eficacia y la farmacocinética (pharmacokinetics, PK) fecal y sistémica. El objetivo principal de la Parte B es evaluar la seguridad y la eficacia de cadazolid en niños desde el nacimiento hasta < 18 años de edad en comparación con vancomicina. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of Part A are to assess the efficacy of cadazolid in terms of Clinical Cure, Sustained Clinical Cure, and Recurrence. Secondary objectives of Part B are to assess the efficacy of cadazolid in terms of Sustained Clinical Cure, Recurrence, time to Recurrence, and time to resolution of diarrhea (ROD) as compared to vancomycin. |
Los objetivos secundarios de la Parte A son evaluar la eficacia de cadazolid en términos de Curación clínica, Curación clínica sostenida y Recurrencia. Los objetivos secundarios de la Parte B son evaluar la eficacia de cadazolid en términos de Curación clínica sostenida, Recurrencia, tiempo hasta la Recurrencia y tiempo hasta la resolución de la diarrea (resolution of diarrhea, ROD) en comparación con vancomicina. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Parts A and B: - Signed informed consent by parents or legally authorized representatives (LAR) and assent by the child according to local requirements prior to initiation of any study-mandated procedure. - Male or female from birth to < 18 years. - Subject is diagnosed with CDAD |
Parte A y B: - Consentimiento informado firmado por padres o representantes legales (legally authorized representative, LAR) y con el asentimiento del niño, según los requisitos locales, antes del inicio de cualquier procedimiento exigido por el estudio. - Paciente femenino o masculino desde el nacimiento hasta < 18 años de edad. - Al paciente se le diagnostica CDAD |
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E.4 | Principal exclusion criteria |
Parts A and B: - Positive Rotavirus test for subjects < 5 years. - Fulminant or life-threatening CDAD - More than one previous episode of CDAD in the 3 month period prior to enrolment/randomization. - Antimicrobial treatment active against CDAD administered within 24 h prior to screening except for metronidazole treatment failures (MTF). - Subjects with body weight < 3 kg. - Inflammatory bowel disease, chronic abdominal pain, or chronic diarrhea of any etiology. - Fecal microbiota transplant (FMT), immunoglobulin therapy, or any investigational drug to prevent or treat CDAD within 1 month period (or 5 half-lives in case of investigational drug, whichever is longer) prior to enrolment/randomization. - Monoclonal antibodies against C. difficile within 6 months prior to enrolment/randomization. - Previous vaccination against C. difficile. - Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject’s full participation in the study, or compliance with the protocol. |
Partes A y B: - Examen de rotavirus positivo en pacientes de < 5 años de edad. - CDAD fulminante o potencialmente mortal. - Más de un episodio previo de CDAD en el período de 3 meses antes del reclutamiento/aleatorización - Tratamiento antimicrobiano activo contra CDAD administrado dentro de las 24 horas previas a la selección, excepto fracasos de tratamiento con metronidazol (metronidazole treatment failures, MTF). - Pacientes con peso corporal < 3 kg. - Enfermedad inflamatoria intestinal, dolor abdominal crónico o diarrea crónica de cualquier etiología. - Trasplante de microbiota fecal (fecal microbiota transplant, FMT), terapia de inmunoglobulina, o cualquier fármaco en investigación para prevenir o tratar la CDAD dentro de un período de 1 mes (o 5 semividas de eliminación en caso de un fármaco en investigación, lo que dure más tiempo) antes del reclutamiento/aleatorización - Anticuerpos monoclonales contra C. difficile dentro de los 6 meses antes del reclutamiento/aleatorización - Vacunación previa contra C. difficile. - Cualquier circunstancia o afección, la cual, en opinión del investigador, pueda afectar la participación completa del paciente en el estudio o el cumplimiento del protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A: Plasma concentrations of cadazolid Faecal concentrations of cadazolid
Part B: Clinical cure |
Parte A: La concentración de cadazolid en plasma La concentración de cadazolid en las heces Parte B: Curación clínica |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- At visit 3 (Part A) for plasma and faecal concentrations of cadazolid - End of treatment + 2 days (Part B) for Clinical cure |
- Concentraciones de cadazolid en plasma y en heces en la visita 3 (Parte A) - Final del tratamiento + 2 días (Parte B) para la curación clínica |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: - Part A + Part B: Sustained Clinical Cure, Recurrence - Part A only: Clinical Cure - Part B only: Time to recurrence, Time to resolution of diarrhea
Secondary safety endpoints (Part A and Part B): - Adverse events, serious adverse-events, adverse events leading to treatment discontinuation - Change from baseline and marked abnormalities in vital signs and laboratory tests
Other secondary endpoints: Acceptability and palatability assessments. |
Criterios de valoración de eficacia secundarios: - Parte A + Parte B: Curación clínica sostenida, Recurrencia - Solo Parte A: Curación clínica - Solo Parte B: Tiempo de recurrencia, Tiempo de resolución de la diarrea Criterios de valoración de eficacia secundarios (Parte A y Parte B): - Acontecimientos adversos, acontecimientos adversos graves, acontecimientos adversos producidos por un tratamiento de discontinuación. - Cambio desde el inicio y anormalidades marcadas en los signos vitales y en los análisis de laboratorio. Otros criterios de valoración secundarios: Evaluaciones de aceptabilidad y palatabilidad. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- End of Treatment (EOT) + 2 days for Clinical Cure (Part A) - From last dose of study treatment to the time of onset of a new episode of diarrhea for Time to recurrence (Part B) - From the first study dose to the first day of resolution of diarrhea for Time to resolution of diarrhea (Part B) - EOT + 28 to 32 days for Sustained Cure and Recurrence (Part A + Part B) - Up to end of study or Up to EOT + 7 days for safety assessments - EOT for palatability and acceptability (Part A + Part B) |
- Fin del tratamiento (End of treatment, EOT) + 2 días para la curación clínica (Parte A) - Desde la última dosis del tratamiento del estudio hasta la fecha de inicio de un nuevo episodio de diarrea para el tiempo de recurrencia (Parte B) - Desde la primera dosis del estudio hasta el primer día de la resolución de la diarrea pare el tiempo de resolución de diarrea (Parte B) - EOT + 28 a 32 días para la curación sostenida y la recurrencia (Parte A + Parte B) - Hasta el final del estudio o hasta el final del EOT + 7 días para las evaluaciones de seguridad - EOT para palatabilidad y aceptabilidad (Parte A + Parte B) |
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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) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Two-part study: Part A = non-controlled, non randomized ; Part B = controlled, randomized |
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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 | 47 |
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 |
Greece |
Hungary |
Italy |
Poland |
Romania |
Spain |
Turkey |
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
|
LVLS |
Última visita del último paciente (Last visit last subject, LVLS) |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |