E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Chagas Disease |
Enfermedad de Chagas crónica |
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E.1.1.1 | Medical condition in easily understood language |
Chagas Disease |
Enfermedad de Chagas |
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E.1.1.2 | Therapeutic area | Diseases [C] - Parasitic Diseases [C03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066500 |
E.1.2 | Term | Chagas disease recurrent |
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 |
Primary objective is to evaluate efficacy of Posaconazole versus placebo in reducing parasitemia measured by qualitative PCR at end of 120 days of follow-up post treatment.. |
Evaluar la eficacia de posaconazol (POS) en comparación con placebo para la reducción de la parasitemia, determinada mediante reacción en cadena de la polimerasa (PCR) cualitativa, al término de 120 días de seguimiento posterior al tratamiento. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include evaluation of safety and tolerability of posaconazole versus placebo, evaluation of relative efficacy and safety of posaconazole versus benznidazole, and evaluation of relative efficacy and safety of benznidazole versus placebo |
Los objetivos secundarios incluyen: Evaluar la seguridad y la tolerabilidad de POS en comparación con placebo, evaluar la eficacia y la seguridad relativas de POS en comparación con benznidazol (BNZ) y evaluar la eficacia y la seguridad relativas de BNZ en comparación con placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Each subject must be 18 to < or = to 50 years of age, of either sex and of any race, weighting > or = to 60 kg, and willing to adhere to visit schedule and study procedures. 2. Each subject must have a positive serology result for T. cruzi on any 2 of 3 of the following tests: IFA, IHA, or ELISA (testing results within the past 10 years). 3. Each subject must have a positive qualitative PCR for T. cruzi. 4. Each subject must have a normal 12-lead ECG, or it must be clinically insignificant. 5. Each subject must have a normal 2-D echocardiogram, or it must be clinically insignificant. 6. Each subject must have no evidence of ventricular tachycardia on a 24-hr Holter monitoring. |
1.Los sujetos deben tener entre 18 y 50 años de edad, ser de cualquier sexo y de cualquier raza, pesar igual o más de 60 kg y estar dispuestos a cumplir con el calendario de visitas y los procedimientos del estudio. 2.Los sujetos deben presentar un resultado serológico positivo para T. cruzi en dos de tres de los siguientes análisis: inmunofluorescencia indirecta, hemoaglutinación indirecta o enzimoinmunoanálisis de adsorción (ELISA) (resultados de análisis obtenidos en los últimos 10 años provenientes de la historia clínica, del médico remitente o del centro de selección.) 3.Los sujetos deben presentar una PCR cualitativa positiva para T. cruzi. 4.Los sujetos deben tener un electrocardiograma (ECG) de 12 derivaciones normal o, si no es normal, las alteraciones halladas no deben tener importancia clínica. 5.Los sujetos deben tener un ecocardiograma bidimensional normal o, si no es normal, las alteraciones halladas no deben tener importancia clínica. 6.Los sujetos no deben presentar signos de taquicardia ventricular en el registro Holter de 24 horas. |
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E.4 | Principal exclusion criteria |
1. Subject must not weigh less than 60 kg. 2. Female subjects must not be breastfeeding, pregnant, or planning pregnancy. 3. Subjects must not be immunodeficient or immunosuppressed. 4. Subjects must not have a history of megacolon with obstipation or megaesophagus with severe swallowing impairment. 5. Subjects must not have previously received benznidazole or nifurtimox. 6. Subjects must not be a family member of a participating subject, or reside in the same household as a participating subject. 7. Subjects must not have AST or ALT levels greater than 2.5 times ULN at screening. 8. Subjects must not have serum creatinine >2.5 mg/dL or 200 micromoles at screening. 9. Subjects must not have a history of severe alcohol abuse within 2 years from screening. 10. Subjects must not be taking any prohibited medications. |
1.Sujetos que pesen < 60 kg. 2.Mujeres en edad fértil que se encuentren amamantando, que estén embarazadas o que tengan la intención de quedarse embarazadas 3.Sujetos con inmunodeficiencia o en tratamiento con inmunodepresores. 4.Sujetos con antecedentes de megacolon con estreñimiento o megaesófago con deterioro intenso de la deglución. 5.Sujetos que hayan sido previamente tratados con BNZ o nifurtimox. 6.Sujetos que sean familiares de un sujeto que ya esté participando en este estudio o que vivan en el mismo hogar que un sujeto que ya esté participando en este estudio. 7.Sujetos con valores de aspartato-aminotransferasa (AST) o alanina-aminotransferasa (ALT) superiores a 2,5 veces el límite superior de la normalidad en la selección. 8.Sujetos con creatinina sérica > 2,5 mg/dl o 200 micromoles en la selección 9.Sujetos con antecedentes de alcoholismo intenso en los dos años anteriores a la selección. 10.Sujetos que tomen cualquiera de los medicamentos prohibidos durante el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of subjects who show a successful response for the posaconazole versus placebo comparison. A successful response is defined as both a negative qualitative PCR on Day 180, and a negative qualitative PCR on at least the two preceding samples. |
El criterio principal de valoración de la eficacia para este estudio es la proporción de sujetos que presenten una respuesta satisfactoria en la comparación de POS con placebo. Se define como respuesta satisfactoria la conjunción de una PCR cualitativa negativa el día 180 o por lo menos las dos muestras precedentes |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 180 (or Day 150 if Day 180 is missing) and Day 120 and 150 (or Day 90 and 120 if Day 180 is missing). |
Día 180 (o día 150 si el día 180 falta) y día 120 y 150 ( o día 90 y 120 si el día 180 falta) |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are the proportion of subjects who show a successful response for the other possible pairwise comparisons with the trial (i.e., posaconazole versus benznidazole, benznidazole versus placebo, posaconazole + benznidazole versus posaconazole, versus benznidazole, versus placebo) and the proportion of subjects with negative qualitative PCR at each individual evaluation during the study. |
Los criterios secundarios de valoración de la eficacia son la proporción de sujetos que presenten una respuesta satisfactoria (como se la definió precedentemente) para las otras comparaciones por pares posibles en este estudio (es decir, POS en comparación con BNZ; BNZ en comparación con placebo y POS + BNZ en comparación con POS, en comparación con BNZ y en comparación con placebo) y la proporción de sujetos con PCR cualitativa negativa en cada una de las evaluaciones individuales realizadas durante el estudio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 30, 60, 90, 120, 150, 180, and 360 |
Días 30, 60, 90, 120, 150, 180 y 360 |
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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) | No |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Simple ciego para Posaconazol, abierto para Benznidazol. |
Single blind for Posaconazole, Open for Benznidazole |
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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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Argentina |
Chile |
Colombia |
Guatemala |
Mexico |
Peru |
Spain |
Venezuela, Bolivarian Republic of |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |