Phase 2a Proof-of-Concept, Multicenter, Randomized, Open Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of the Combination M5717-pyronaridine as Chemoprevention in Asymptomatic Adults and Adolescents With Plasmodium Falciparum Malaria Infection (CAPTURE-2)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 192
- 试验地点
- 4
- 主要终点
- Time to Parasitemia Since Negative Blood Smear After Treatment
研究概览
简要总结
This study evaluates the efficacy and safety of a single dose of M5717 plus pyronaridine tetraphosphate in clearing current Plasmodium falciparum infection and protecting against recurrent infections in asymptomatic adults and adolescents. The study will also assess the duration of protection provided by different doses of M5717 plus pyronaridine and the additional contribution of M5717 to the duration of protection using external study data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with Asymptomatic Plasmodium falciparum Malaria with no Fever or other sign of Acute Uncomplicated Malaria and, with Microscopic confirmation using Giemsa-stained thick film, and a Parasitemia of >= 40 to <= 10,000 Asexual Parasites/Microliter (μL) of Blood.
- •Axillary Temperature < 37.0 degree Celcius (ºC) or oral/Tympanic/rectal Temperature< 37.5ºC; without history of fever during the previous 48 hours.
- •Have a body weight >= 45 kilogram (kg)
- •Participants capable of giving Signed Informed consent which includes Compliance with the requirements and restriction listed in the Informed consent form
- •Other Protocol defined Inclusion Criteria could apply
排除标准
- •Participants with any disease requiring Chronic Treatment
- •Participants with any Preplanned surgery during the study
- •Participants with any previous Treatment with pyronaridine as part of a combination therapy during the last 3 months
- •Participants with any adequate Hematological, Hepatic, and renal function as defined in the Protocol
- •Other protocol defined Exclusion Criteria could apply
研究组 & 干预措施
Cohort 1: M5717 (60 mg) + Pyronaridine
Participants received single oral dose of M5717 60 milligram (mg) plus pyronaridine tetraphosphate (pyronaridine) 720 mg (Participants >= 65 kilogram [kg]) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
干预措施: M5717 60 mg (Drug)
Cohort 1: M5717 (60 mg) + Pyronaridine
Participants received single oral dose of M5717 60 milligram (mg) plus pyronaridine tetraphosphate (pyronaridine) 720 mg (Participants >= 65 kilogram [kg]) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
干预措施: Pyronaridine (Drug)
Cohort 2: M5717 (200 mg) + Pyronaridine
Participants received single oral dose of M5717 200 mg plus pyronaridine 720 mg (Participants >= 65 kg) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
干预措施: Pyronaridine (Drug)
Cohort 2: M5717 (200 mg) + Pyronaridine
Participants received single oral dose of M5717 200 mg plus pyronaridine 720 mg (Participants >= 65 kg) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
干预措施: M5717 200 mg (Drug)
Cohort 3: M5717 (660 mg)+ Pyronaridine
Participants received single oral dose of M5717 660 mg plus pyronaridine 720 mg (Participants >= 65 kg) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
干预措施: Pyronaridine (Drug)
Cohort 3: M5717 (660 mg)+ Pyronaridine
Participants received single oral dose of M5717 660 mg plus pyronaridine 720 mg (Participants >= 65 kg) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
干预措施: M5717 660mg (Drug)
Cohort 4: Atovaquone-proguanil
Participants received orally 3 doses of Malarone (fixed-dose combination of atovaquone-proguanil) once daily in a 3-day treatment regimen.
干预措施: Atovaquone-Proguanil (Drug)
结局指标
主要结局
Time to Parasitemia Since Negative Blood Smear After Treatment
时间窗: From treatment Day 1 up to End of observation period Day 64 (Week 10)
The time (in days) to first recorded parasitemia (parasite count \>0) since the first negative blood smear (parasite count of 0) after treatment (followed at least by 1 subsequent visit with a negative blood film), i.e. the time without a positive blood smear. Median time and 95% CI was estimated using the Kaplan Meier method for each cohort.
次要结局
- Parasite Clearance Time(Time from dosing to the first negative (no parasites) blood film (microscopy) , assessed up to 12 weeks)
- Percentage of Participants With Parasitemia (Positive Blood Smear)(From treatment Day 1 up to End of observation period Day 64 (Week 10))
- Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Parasitemia (Due to New Infections)(From treatment Day 1 up to End of observation period Day 64 (Week 10))
- Percentage of Participants With PCR-adjusted Parasitemia (Due to Recrudescence)(From treatment Day 1 up to End of observation period Day 64 (Week 10))
- Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Treatment Related TEAEs(Up to End of Study (approximately 12 Weeks))
- Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 and Pyronaridine(Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2)
- Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 and Pyronaridine(Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2)
- Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 and Pyronaridine(Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2)
- Apparent Total Body Clearance From Blood (CL/f) of M5717 and Pyronaridine(Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2)
- Maximum Observed Blood Concentration (Cmax) of M5717 and Pyronaridine(Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2)
- Apparent Terminal Half-life (t1/2) of M5717 and Pyronaridine(Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2)
- Time to Reach the Maximum Blood Concentration (Tmax) of M5717 and Pyronaridine(Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2)
- Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 and Pyronaridine(Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2)