E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clostridium difficile-associated diarrhea (CDAD) |
Diarrea Asociada a Clostridium Difficile (DACD) |
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E.1.1.1 | Medical condition in easily understood language |
Intestinal infection due to Clostridium difficile |
Infección Intestinal debido 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 | 16.1 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether the clinical response after 10-day oral administration of cadazolid is non-inferior to oral vancomycin in subjects with CDAD. |
Determinar si la respuesta clínica después de la administración oral de cadazolid durante 10 días no es inferior a la de la vancomicina oral en sujetos con DACD. |
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E.2.2 | Secondary objectives of the trial |
To determine whether oral administration of cadazolid for 10 days is superior to oral vancomycin in the sustained clinical response of subjects with CDAD. To determine whether the resolution of diarrhea (ROD) is more rapid with oral administration of cadazolid compared to vancomycin. To determine whether CDAD symptoms, as reported by the subject, show larger improvements from baseline with oral administration of cadazolid compared to vancomycin. |
Determinar si la administración oral de cadazolid durante 10 días es superior a la de vancomicina oral en la respuesta clínica mantenida en sujetos con DACD. Determinar si la resolución de la diarrea (RD) es más rápida con la administración oral de cadazolid en comparación con vancomicina. Determinar si los síntomas de DACD notificados por el sujeto muestran mayores mejorías respecto al inicio con la administración oral de cadazolid en comparación con vancomicina. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Psychometric validation of CDAD DaySyms PRO
objective: To demonstrate the final content validity of the CDAD-DaySyms including the scoring algorithm; to demonstrate the psychometric characteristics of reliability and construct validity of the CDAD-DaySyms; and to demonstrate the ability of the CDAD-DaySyms to detect change.
-Gut microbiome assessment and fecal cadazolid concentrations
objective: analyze intestinal flora diversity and its variation on treatment and after treatment, the emergence of resistance, and evaluating the fecal cadazolid concentration |
- Validación psicométrica del CDAD DaySyms PRO
Objetivo: Demostrar la validez del contenido final del CDAD DaySyms PRO incluyendo la valoración algorítmica; demostrar las características psicométricas de fiabilidad y construir la validez del CDAD DaySyms; y demostrar la habilidad del CDAD DaySyms para detectar el cambio |
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E.3 | Principal inclusion criteria |
- Signed Informed Consent. - Male or female >or= 18 years of age. Females of childbearing potential must agree to use an adequate and reliable method of contraception. - Subject with a diagnosis of mild-moderate or severe CDAD (first occurrence or first recurrence within 3 months) with: Diarrhea: a change in bowel habits with > 3 liquid or unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile toxin test on a stool sample produced within 72 hours prior to randomization. |
1. Consentimiento informado firmado. 2. Varones o mujeres de >o= 18 años. Mujeres en edad fértil deberán usar un métido adecuado y seguro de contracepción. 3. Sujeto con diagnóstico de DACD leve a moderada o intensa (primer episodio o primera recurrencia en los 3 meses previos a la aleatorización) con: - Diarrea, definida como un cambio del hábito intestinal con > 3 deposiciones líquidas o Deposición Blanda (DB) en las 24 horas previas a la aleatorización Y - Prueba positiva en heces de la toxina de C. difficile en una muestra recogida no más de 72 horas antes de la aleatorización. |
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E.4 | Principal exclusion criteria |
- More than one previous episode of CDAD in the 3-month period prior to randomization. - Evidence of life-threatening or fulminant CDAD. - Likelihood of death within 72 hours from any cause. - History of inflammatory colitides, chronic abdominal pain, or chronic diarrhea. - Antimicrobial treatment active against CDAD administered for > 24 hours except for metronidazole treatment failures (MTF) - Known hypersensitivity or contraindication to study drugs, oxazolidinones, or quinolones. - Unable or unwilling to comply with all protocol requirements. |
1. Más de un episodio previo de DACD en el período de 3 meses previo a la aleatorización. 2. Evidencia de DACD fulminante o amenazante para la vida. 3. Probabilidad de muerte en 72 h por cualquier causa. 4. Antecedentes de colitis inflamatoria, dolor abdominal crónico o diarrea crónica. 5. Tratamiento antimicrobiano activo frente a la DACD administrado durante > 24 horas, a excepción de los fracasos del tratamiento con metronidazol 6. Hipersensibilidad conocida o contraindicación al fármaco en investigación, o a oxazolidinonas o quinolonas. 7. Incapacidad o falta de disposición para cumplir todos los requisitos del protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical Cure defined as: - Resolution of Diarrhea (ROD: ? or = 3 UBMs per day for at least 2 consecutive days) on study treatment, maintained for 2 days after End of Treatment (EOT) AND - No additional antimicrobial treatment active against CDAD or Fetal micobiotic Transplan (FMT) between first dose and 2 days after EOT (inclusive). |
Curación clínica, definida como: - Resolución de la diarrea (RD: < o = 3 DB al día durante al menos 2 días consecutivos) durante el tratamiento del estudio, mantenida durante 2 días después del Final del Tratamiento (FT) Y - Ausencia de tratamiento antimicrobiano adicional activo frente a la DACD o Trasplante de Microflora Fecal (TMF) entre la primera dosis y 2 días después del FT (inclusive). |
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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) |
Sustained Cure defined as: - Clinical Cure AND - No Recurrence Recurrence is defined for subjects with Clinical Cure as: - New episode of diarrhea (NED: > 3 UBMs within 1 day) occurring between 3 days and visit 5 after EoT AND - Positive C. difficile toxin stool test AND - Antimicrobial treatment active against CDAD or FMT started between 3 days and visit 5 (or participation in the re-treatment extension with cadazolid).
Time to ROD, defined as: - The time (h) elapsed between the first dose of study drug and the time when ROD is considered achieved.
Absolute change from baseline in CDAD DaySyms Patient Reported Outcomes (PRO). CDAD DaysSyms total daily score change from baseline up to Day 12. |
Curación mantenida, definida como: - Curación clínica Y - Ausencia de recurrencia En los sujetos con curación clínica, la recurrencia se define como: - Nuevo episodio de diarrea (NED: > 3 DB en 1 día) aparecido entre 3 días después del FT y la visita 5 Y - Prueba de toxina de C. difficile en heces positiva Y - Inicio de tratamiento antimicrobiano activo frente a la DACD o TMF entre 3 días después del FT y la visita 5 (o participación en la extensión de retratamiento con cadazolid). Tiempo hasta la RD, definido como: - Tiempo (h) transcurrido entre la primera dosis del fármaco del estudio y el momento en que se considera lograda la RD. Cambio absoluto respecto al inicio en el cuestionario CDAD DaySyms PRO. Cambio de la puntuación diaria total del CDAD DaysSyms desde el inicio hasta el día 12. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Canada |
Italy |
Romania |
Australia |
Brazil |
Germany |
Spain |
Peru |
Poland |
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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The end of the trial occurs when all the subjects have completed Visit 5 or Re-5 for those participating in the re-treatment extension with cadazolid. |
El final del estudio ocurre cuando todos los pacientes han completado la visita 5 o RE-5 para aquellos que participen en la extensión de tratamiento con cadazolid |
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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 | 11 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |