E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients affected by uncomplicated Plasmodium vivax malaria |
Pacientes con paludismo no complicado debido a Plasmodium vivax |
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E.1.1.1 | Medical condition in easily understood language |
Patients with imported uncomplicated Plasmodium vivax malaria, contracted in endemic countries |
Pacientes con paludismo importado no complicado debido a Plasmodium vivax, contraído en países endémicos |
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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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10035503 |
E.1.2 | Term | Plasmodium vivax 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 evaluate the efficacy of an Eurartesim® treatment course in patients with imported uncomplicated P. vivax malaria. The efficacy will be primarily assessed as uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 21 of follow-up. |
Evaluar la eficacia de un tratamiento de Eurartesim® en pacientes con paludismo importado no complicado debido a P. vivax. La eficacia se evaluará principalmente como ACPR no corregida en el día 21 del seguimiento. |
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E.2.2 | Secondary objectives of the trial |
Proportion of aparasitaemic patients (at different visits). Proportion of afebrile patients (at different visits). Day 42 uncorrected ACPR. Proportion of patients with Treatment Failure. |
Proporción de pacientes libres de parásitos (en las diferentes visitas).
Proporción de pacientes sin fiebre (en las diferentes visitas).
Día 42 ACPR no corregido.
Proporción de pacientes con fracaso del tratamiento.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Have read the Information for the Patient and signed the Informed Consent Form;
2.Aged ≥18 years;
3.Ability to swallow oral medication;
4.Body weight comprised between 24 kg and 100 kg (included) for males and females;
5.Uncomplicated malaria with microscopically confirmed monoinfection by Plasmodium vivax or mixed infection (i.e. infection with P. vivax and other Plasmodium species);
6.Willingness to comply with the study protocol and the study visit schedule. |
1.Haber leído la información para el paciente y haber leído el Formulario de Consentimiento Informado;
2.Edad ≥18 años;
3.Capacidad de tragar medicación oral;
4.Peso corporal de entre 24 kg y 100 kg (ambos incluidos) para los hombres y las mujeres;
5.Paludismo no complicado con monoinfección confirmada por microscopio debida a Plasmodium vivax o infección mixta (es decir, infección con P. vivax y otras especies de Plasmodium);
6.Voluntad de realizar el protocolo del estudio y el programa de visitas del estudio.
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E.4 | Principal exclusion criteria |
1.Participation in any investigational drug study during the previous 30 days;
2.Antimalarial treatment with chloroquine and quinine within the previous 6 weeks, with piperaquine-based compounds or mefloquine or lumefantrine within the previous 3 months and with halofantrine within the previous 30 days prior to screening;
3.Known hypersensitivity to piperaquine and/or dihydroartemisinin;
4.P. vivax/Plasmodium species asexual stage parasitaemia ≥ 5% RBCs (in cases of mixed infection);
5.Clinical and/or laboratory features of severe malaria according to WHO criteria (WHO 2010);
6.ECG abnormality that requires urgent management (i.e. clinically significant arrhythmias, AV block II and III degree etc.);
7.Family history of sudden death, or known congenital prolongation of the QT interval
8.Lengthening of QT interval on ECG: QTc (Fridericia’s correction) ≥450 ms for males and ≥470 ms for females;
9.Concomitant administration of any treatment which can induce a lengthening of QT interval (i.e. antihistamines, macrolides, etc.) and of any antimalarial drugs (for the full list of prohibited drugs refer to section 8.3);
10.Any contraindication to blood sampling (i.e. important haemorrhagic diathesis);
11.Presence of intercurrent illness or any condition (i.e. severe vomiting and dehydration) which in the judgement of the Investigator would place the patient at undue risk or interfere with the study results;
12.Hypoglycaemia (blood glucose levels < 2.2 mmol/L or < 40 mg/dL);
13.Splenectomy;
14.Pregnant or lactating women. During the study period (Day 0- Day 42), fertile women who are sexually active must use an adequate birth control method. They should utilize oral or patch contraceptives, contraceptive implant or depot injection or an intrauterine device from at least one month before screening and during the whole study period. In all the other cases they have to agree to remain inactive or use condoms with a spermicidal agent during the study period;
15.Presence of jaundice;
16.Known renal impairment (serum creatinine > 2X the upper limit of the hospital laboratory reference range);
17.Known liver insufficiency (AST and/or ALT > 3X the upper limit of the hospital laboratory reference range);
18.Relevant anaemia (Hb< 8 g/dL).
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1.Haber participado en cualquier estudio de medicamentos en los 30 días anteriores;
2.Haber recibido tratamiento contra el paludismo con cloroquina y quinina en las 6 semanas anteriores, con compuestos con base de piperaquina o con mefloquina o lumefantrina en los 3 meses anteriores y con halofantrine en los 30 días anteriores a la exploración;
3.Hipersensibilidad conocida a la y/o a la dihidroartemisinina;
4.Especies P. vivax/Plasmodium parasitemia de fase asexual ≥ 5% RBCs (en casos de infección mixta);
5.Características clínicas y/o de laboratorio de paludismo grave según los criterios de la OMS (OMS 2010);
6.Anormalidad de ECG que requiere gestión urgente (por ej., arritmias clínicamente significativas, bloqueo AV de grado II y III, etc.);
7.Antecedentes familiares de muerte súbita o prolongación congénita conocida del intervalo QT.
8.Alargamiento del intervalo QT en ECG: QTc (corrección de Fridericia) ≥450 ms para hombres y ≥470 ms para mujeres;
9.Administración concomitante de cualquier tratamiento que pueda inducir un alargamiento del intervalo QT (por ej., antihistaminicos, macrólidos, etc.) y cualquier medicamento contra el paludismo (para la lista completa de medicamentos prohibidos, consulte la sección 8.3);
10.Cualquier contraindicación a la toma de muestras de sangre (por ej., diatesis hemorrágica importante);
11.Presencia de enfermedad intercurrente o cualquier problema (por ej., vómitos y deshidratación graves) que en la opinión del investigador provocarían una interferencia o riesgo indebidos en el paciente con los resultados del estudio;
12.Hipoglucemia (niveles de glucosa en sangre < 2,2 mmol/L o < 40 mg/dL);
13.Esplenectomía;
14.Embarazo o lactancia. Durante el período de estudio (día 0 - día 42), las mujeres fértiles sexualmente activas deben utilizar un método anticonceptivo adecuado. Deberían utilizar anticonceptivos orales o parches, implantes anticonceptivos o por inyección o un dispositivo intrauterino desde al menos un mes antes de la exploración durante todo el período del estudio. En todos los demás casos, deben aceptar utilizar preservativos con un agente espermicida o permanecer inactivas durante el período del estudio.
15.Presencia de ictericia;
16.Deterioro renal conocido (medición de creatinina, suero > 2X el límite máximo del laboratorio del hospital de referencia);
17.Insuficiencia hepática insuficiente (AST y/o ALT > 3X el límite máximo del laboratorio del hospital de referencia);
18.Anemia relevante (Hb< 8 g/dL). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Uncorrected Adequate Clinical and Parasitological Response (ACPR). |
Respuesta clínica y parasitológica adecuada (ACPR) no corregido. |
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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) |
Proportion of aparasitaemic patients; Proportion of afebrile patients;
Uncorrected ACPR;
Treatment Failure |
Proporción de pacientes libres de parásitos Proporción de pacientes sin fiebre
Día 42 ACPR no corregido.
Tracaso del tratamiento.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1, Day 2, Day 7 (±1), Day 21(+2) and Day 42(±2) as well as at any additional visits;
Day 1, Day 2, Day 7 (±1), Day 21(+2) and Day 42(±2) as well as at any additional visits;
Day 42(±2);
Any time during the study course |
Día1, Día 2, Día 7 (±1), Día 21(+2) y Día 42(±2) así como en cualquier visita adicional.;
Día 1, Día 2, Día 7 (±1), Día 21(+2) y Día42(±2) así como en cualquier visita adicional.;
Día 42(±2);
en cualquier momento durante el estudio |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
France |
Italy |
Netherlands |
Germany |
Spain |
Israel |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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 | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |