A Randomized, Open Label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 Dose Levels of Artefenomel (OZ439) Given in Combination With Ferroquine (FQ) and FQ Alone, in African Patients With Uncomplicated Plasmodium Falciparum Malaria
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 140
- 试验地点
- 7
- 主要终点
- Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)
研究概览
简要总结
Primary Objective:
To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor.
Secondary Objectives:
- To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR.
- To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR.
- To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints.
- To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone.
- To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.
详细描述
The duration of the study was up to 32 days, including up to 1 day screening period before the single-dose treatment, 5 days of post-treatment surveillance (included 2 to 4 days hospitalization) and 24±2 days follow-up period.
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
- 14 Years 至 69 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ferroquine 400 mg + Artefenomel 1000 mg
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
干预措施: Ferroquine (SSR97193) (Drug)
Ferroquine 400 milligram (mg)
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
干预措施: Ferroquine (SSR97193) (Drug)
Ferroquine 400 mg + Artefenomel 300 mg
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
干预措施: Artefenomel (OZ439) (Drug)
Ferroquine 400 mg + Artefenomel 300 mg
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
干预措施: Ferroquine (SSR97193) (Drug)
Ferroquine 400 mg + Artefenomel 600 mg
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
干预措施: Artefenomel (OZ439) (Drug)
Ferroquine 400 mg + Artefenomel 600 mg
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
干预措施: Ferroquine (SSR97193) (Drug)
Ferroquine 400 mg + Artefenomel 1000 mg
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
干预措施: Artefenomel (OZ439) (Drug)
结局指标
主要结局
Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)
时间窗: Day 28
ACPR:absence of parasitemia at Day 28, irrespective of axillary temperature(AT), participants not meeting any criteria of early therapy failure(ETF):Danger signs(DS)/symptoms of complicated(SoC)/severe malaria(SM) at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia;or parasitemia on Day 2 \>Day 0 irrespective of AT;or parasitemia on Day 3 with AT\>=37.5 degree Celsius (°C);or parasitemia count on Day 3 \>=25 percent (%) on Day 0, or late clinical failure (LCF):DS/SM in presence of parasitemia between Day 4 and 28,concomitant to at least one positive parasitemia;or presence of parasitemia and AT\>=37.5°C on Day 4 to Day 28, or late parasitological failure(LPF):presence of parasitemia between Day 7 and 28 and AT\<37.5°C and without rescue therapy. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with reinfection.
次要结局
- Time to Re-infection(Up to Day 28)
- Time to 50% and 99% Parasite Reduction(Up to Day 28)
- Parasite Clearance Time (PCT)(From the start of study drug administration up to the time of the first negative blood film (up to Day 28))
- Parasite Clearance Rate(Up to Day 28)
- Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel(Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose)
- Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28(Day 28)
- Time to Re-emergence(Up to Day 28)
- Time to Recrudescence(Up to Day 28)
- Pharmacokinetics (PK): Concentration of OZ439 in Plasma(1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose)
- Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours(Baseline, 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post-dose)
- Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours(Baseline, 24, 48 and 72 hours post-dose)
- Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia(Up to Day 28)
- Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel(Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose)
- Pharmacokinetics: Time to Reach Maximum Plasma Concentration (Tmax) of Artefenomel(Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)(From Baseline up to Day 28)
- Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood(1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose)
- Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel(At 168 hours post-dose)
- Pharmacokinetics: Terminal Half-life (t1/2) of Artefenomel(Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose)
- Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213(Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose)
- Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213(Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose)
- Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213(Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose)
- Pharmacokinetics: Time to Reach Maximum Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213(Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose)
- Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213(At 168 hours post-dose)
- Pharmacokinetics: Terminal Half-life of Ferroquine(Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose)