E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clostridium difficile-associated diarrhea (CDAD) |
Diarrea Associata a Clostridium difficile |
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E.1.1.1 | Medical condition in easily understood language |
Intestinal infection due to Clostridium difficile |
Infezione intestinale da 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.
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L’obiettivo primario della Parte A è determinare la dose di cadazolid nei bambini dalla nascita a < 18 anni di età analizzando la sicurezza, l’efficacia e la farmacocinetica (Pharmacokinetics, PK) sistemica e fecale.
L’obiettivo primario della Parte B è valutare la sicurezza e l’efficacia di cadazolid nei bambini dalla nascita a < 18 anni di età rispetto alla 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. |
Gli obiettivi secondari della Parte A sono valutare l’efficacia di cadazolid in termini di guarigione clinica, guarigione clinica sostenuta e recidiva.
Gli obiettivi secondari della Parte B sono valutare l’efficacia di cadazolid in termini di guarigione clinica sostenuta, recidiva, tempo alla recidiva e tempo alla risoluzione della diarrea (Resolution Of Diarrhea, ROD) rispetto alla 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 |
Part A e B:
- Consenso informato firmato dai genitori o dai rappresentanti legalmente riconosciuti (Legally Authorized Representative, LAR) e assenso del bambino, in base ai requisisti locali prima dell’inizio di qualsiasi procedura prevista dallo studio.
- Sesso maschile o femminile ed età compresa tra la nascita e < 18 anni.
- Soggetti con diagnosi di 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. |
Parte A e B
- Test rotavirus positivo per i soggetti di età < 5 anni.
- CDAD fulminante o potenzialmente letale.
- Più di un precedente episodio di CDAD nei 3 mesi precedenti l’arruolamento/la randomizzazione.
- Trattamento antimicrobico attivo contro la CDAD somministrato nelle 24 ore precedenti lo screening, eccetto fallimenti del trattamento con metronidazolo (Metronidazole Treatment Failure, MTF).
- Soggetti con peso corporeo < 3 kg.
- Malattia infiammatoria intestinale, dolore addominale cronico o diarrea cronica di qualsiasi eziologia.
- Trapianto di microbiota fecale (Fecal Microbiota Transplant, FMT), terapia con immunoglobuline o qualsiasi farmaco sperimentale per prevenire o trattare la CDAD entro 1 mese (o 5 emivite in caso di farmaco sperimentale, a secondo di quale dei due periodi è il più lungo) precedente l’arruolamento/la randomizzazione.
- Anticorpi monoclonali contro C. difficile nei 6 mesi precedenti l’arruolamento/la randomizzazione.
- Precedente vaccinazione contro C. difficile.
- Eventuali circostanze o condizioni che, a giudizio dello sperimentatore, possano influenzare la piena partecipazione del soggetto allo studio, o la conformità al protocollo.
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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:
Concentrazione plasmatica di cadazolid
Concentrazione nelle feci di cadazolid
Part B:
Guarigione clinica
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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 |
- visita 3 (Parte A) per la concentrazione plasmatica e nelle feci di cadazolid
- Fine del trattamento + 2 giorni (Parte B) per guarigione clinica
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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. |
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
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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) |
- 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)
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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 |
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 |
Germany |
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
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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 | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 0 |