NCT04300309终止2 期
Multicenter, Open-label, Single-arm Study to Evaluate the PK, Safety, Tolerability and Efficacy of a New Artemether:Lumefantrine (2.5 mg:30 mg) Dispersible Tablet in the Treatment of Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 3
- 主要终点
- Artemether Cmax After First Dose
研究概览
简要总结
The purpose of this study was to evaluate PK, safety, tolerability and efficacy of a new formulation of artemether-lumefantrine dispersible tablet in neonates and infants <5 kg body weight with acute uncomplicated Plasmodium falciparum malaria.
详细描述
This was a multicenter, open-label, single-arm, adaptive design with dose adaptation (deescalation or escalation) study in infants and neonates <5 kg body weight with P. falciparum malaria. There were two sequential and age-descending cohorts of participants, all <5 kg: Cohort 1 of infants >28 days of age, and Cohort 2 of neonates ≤ 28 days of age.
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
- — 至 365 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female neonates/infants
- •Body weight <5 kg but ≥ 2 kg
- •In Cohort 1, infants aged >28 days; in Cohort 2, neonates aged 1 to ≤28 days (3 subgroups: 1-7 days; 8-14 days; 15-28 days)
- •Microscopically confirmed diagnosis of P. falciparum malaria (or mixed infections):
- •in Cohort 1 of ≥500 and <100,000 parasites/µL asexual P. falciparum parasitemia
- •in Cohort 2 of ≥100 and <100,000 parasites/µL asexual P. falciparum parasitemia
- •either congenital or neonatal
- •either symptomatic or asymptomatic
排除标准
- •Head circumference < - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly)
- •Presence of severe malaria (according to WHO 2015 definition)
- •HIV status :
- •in Cohort 1, patient's or patient's mother's current treatment with ARV
- •in Cohort 2, mother's known HIV positive status at patient's birth or mother's current treatment with ARV
- •Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants) (WHO 2005)
- •Presence of any clinically significant neurological condition:
- •any episode of convulsion during the present illness (in keeping with the IMCI list of general danger signs)
- •known neurological disorders (e.g. chronic seizure disorders, cerebral palsy)
- •Presence of clinically significant abnormality of the hepatic and renal systems
- •Patients unable to swallow or whose drinking is impaired
- •Known hypersensitivity of the patient or either patient's parent to artemether, lumefantrine, any of the excipients of Coartem®/Riamet® Dispersible tablet, or to drugs of similar chemical classes
- •History of malabsorption or previous gastrointestinal surgery, or history of radiation therapy that could affect drug absorption or metabolism, or any other disorder or history of a condition that could interfere with drug absorption, distribution, metabolism, or excretion
- •Known family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
- •Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)
- •Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities
- •Patients who received any antimalarial drug, including antibiotics with antimalarial activity, within 14 days of trial start, or any other prohibited drug (see Table 6-2)
- •Patients who received an investigational drug within 5 half-lives of enrollment or participated in an investigational study or within 30 days, whichever is longer
研究组 & 干预措施
artemether lumefantrine (2.5 mg:30 mg)
Experimental
Artemether-lumefantrine (5 mg:60 mg) twice daily for 3 days
干预措施: artemether:lumefantrine (2.5 mg:30 mg) (Drug)
结局指标
主要结局
Artemether Cmax After First Dose
时间窗: 1 and 2 hours after first dose (Day 1)
Artemether Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on artemether plasma concentrations.
次要结局
- Lumefantrine Day 8 Concentration (C168h)(168 hours after first dose (corresponding to 108 hours after last dose))
- Lumefantrine Cmax After Last Dose(62, 66, 68 and 84 hours after first dose (corresponding to 2, 6, 8 and 24 hours after last dose))
- DHA Cmax After First Dose(1 and 2 hours after first dose (Day 1))
- Parasite Clearance Time (PCT)(Up to 48 hours after first dose)
- Fever Clearance Times (FCT)(Up to 36 hours after first dose)
- PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis(Days 15, 29 and 43)
- PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis(Days 15, 29 and 43)
- PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR)(Days 8, 15, 29 and 43)
- Number of Participants With Recrudescence Events(Days 15, 29 and 43)
- Number of Participants With New Infections Events(Days 15, 29 and 43)
- Number of Participants With Adverse Events (AEs)(From first dose of study treatment until Day 43)
- Number of Participants With Serious Adverse Events (SAEs)(From first dose of study treatment until 12 months of age (assessed up to maximum 1 year))
研究者
研究点 (3)
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