E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients affected by uncomplicated Plasmodium vivax malaria |
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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 |
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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. |
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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. |
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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. |
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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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E.5 End points |
E.5.1 | Primary end point(s) |
Uncorrected Adequate Clinical and Parasitological Response (ACPR). |
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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 |
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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 |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 |
Israel |
Switzerland |
United Kingdom |
France |
Germany |
Belgium |
Italy |
Netherlands |
Spain |
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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 |