Proof of Concept Study of Eurartesim® in Patients With Imported Uncomplicated Plasmodium Vivax Malaria
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 13
- 主要终点
- Uncorrected adequate clinical and parasitological response (ACPR)
研究概览
简要总结
The aim of the present study is to investigate the efficacy, safety and tolerability of a therapeutic course of Eurartesim® in travellers who contracted malaria due to infection by P. vivax in endemic countries.
详细描述
Vivax malaria occurs throughout the tropical, subtropical and some of the temperate latitudes globally. During a primary infection some P. vivax parasites become dormant in the liver (hypnozoites) during large periods of time and might subsequently cause multiple blood-stage relapses.
The asexual stages of P. vivax are generally still sensitive to chloroquine (CQ) throughout most of the world with the exception of Indonesia and Papua New Guinea where high therapeutic failure rates ranging from 5-84% have been reported. Also, there are reports of chloroquine failure from other countries and regions where the species is endemic; in particular, the presence of CQ-resistant vivax strains is now well described in several countries, including India, Brazil, Peru and Colombia.
The treatment of the dormant stages and the prevention of relapses is reached throughout the 8-aminoquinolines (primaquine is the only commercially available in this indication).
The current treatments recommended by World Health Organization (WHO) for the radical cure of CQ-resistant vivax malaria are Artemisinin based Combination Therapies (ACTs) with partner drugs having very long half-life, combined with a two weeks regiment of primaquine (WHO, 2010).
Among a variety of suitable artemisinin-based combinations, the fixed combination of dihydroartemisinin (DHA) and piperaquine (PQP )is considered an excellent therapeutic approach since it has got all the requirements considered essential for showing a positive benefit/risk ratio in malaria therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have read the Information for the Patient and signed the Informed Consent Form;
- •Aged ≥18 years and able to swallow oral medication;
- •Body weight comprised between 24 kg and 100 kg (included) for males and females;
- •Uncomplicated malaria with microscopically confirmed monoinfection by Plasmodium vivax or mixed infection (i.e. infection with P. vivax and other Plasmodium species);
- •Willingness to comply with the study protocol and the study visit schedule.
排除标准
- •Participation in any investigational drug study during the previous 30 days;
- •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;
- •P. vivax/Plasmodium species asexual stage parasitaemia ≥ 5% Red Blood Cells (in cases of mixed infection);
- •Clinical and/or laboratory features of severe malaria according to WHO criteria (WHO 2010);
- •ECG abnormality that requires urgent management (i.e. clinically significant arrhythmias, Atrio-Ventricular block II and III degree etc.);
- •Family history of sudden death, or known congenital prolongation of the QT interval
- •Lengthening of QT interval on ECG: corrected QT interval (Fridericia's correction) ≥450 ms for males and ≥470 ms for females;
- •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);
- •Any contraindication to blood sampling (i.e. important haemorrhagic diathesis);;
- •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;
- •Hypoglycaemia (blood glucose levels < 2.2 mmol/L or < 40 mg/dL);
- •Splenectomy;
- •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;
- •Presence of jaundice;
- •Known renal impairment (serum creatinine > 2X the upper limit of the hospital laboratory reference range);
- •Known liver insufficiency (AST and/or ALT > 3X the upper limit of the hospital laboratory reference range);
- •Relevant anaemia (Hb< 8 g/dL).
研究组 & 干预措施
Eurartesim tablets
Eurartesim 320 mg piperaquine / 40 mg dihydroartemisinin film coated tablets. one or more tablets according to the body weight, once a day dor three consecutive days.
干预措施: Eurartesim tablets (Drug)
结局指标
主要结局
Uncorrected adequate clinical and parasitological response (ACPR)
时间窗: 21 days after the start of treatment
The uncorrected ACPR will be considered met for all those patients that are not presenting parasitaemia and fever at day 21 follow-up visit.
次要结局
- Proportion of aparasitaemic patients(at day 1, 2, 3, 7, 21, 42)
- Proportion of afebrile patients(at day 1, 2, 3, 7, 21, 42)
- uncorrected ACPR(at day 42)
- Number of Patients with Serious and Non-Serious Adverse Events(up to 42 days from starting of treatment)