Open-label, Dose-finding, 2-parts, Efficacy Phase II Study With Three Formulations (Racemate Raziquantel Commercial Oral Tablets, New Oral Disintegrating Tablets of Racemate Praziquantel and L-praziquantel) in Schistosomiasis (S. Mansoni) Infected Children Aged 2-6 Years (Part 1), Followed by an Assessment of Efficacy and Safety With the Selected Formulation and Dosage in S. Mansoni Infected Infants Aged 3-24 Months (Part 2)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 444
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinical Cure Determined by Kato-Katz Method
研究概览
简要总结
The Phase II study consisted of two parts, part 1 is open label, randomized, controlled and exploratory dose finding in children aged between 2 and 6 years infected with S. mansoni. Part 2 investigated efficacy and safety with the selected formulation and dosage in S. mansoni infected children aged between 3 months - 2 years.
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
- 3 Months 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female children aged 2 to 6 years (Part 1) and 3 to 24 months (Part 2)
- •S. mansoni positive diagnosis defined as positive egg counts in stool (greater than [>]1 egg/1 occasion) according to World Health Organization (WHO) classification : light (1-99 eggs per gram of faeces), moderate (100-399 eggs per gram of faeces) and heavy (greater than or equal to [>=]400 eggs per gram of faeces) infections
- •Minimum weight of 8.0 kg in 2- to 6-year-old children and of 4.0 kg in 3- to 24-month infants
- •Parents/legal representative ability to communicate well with the Investigator, to understand the protocol requirements and restrictions, and willing their children to comply with the requirements of the entire trial, i.e.
- •To be examined by a study physician at screening and 14-21 days after treatment
- •To provide stool and urine samples at screening, 24 hours and 8 days after treatment, as well as 14-21 days after treatment
- •To provide finger prick blood samples for Pharmacokinetics (PK) studies and blood samples for safety assessments
排除标准
- •Treatment in the 4 weeks prior to study screening with Praziquantel (PZQ) , other anti-helminthic, antimalarial or anti-retroviral compounds or any other medication that might affect the PK of PZQ such as certain antiepileptics (e.g., carbamazepine or phenytoin), glucocorticosteroids (e.g., dexamethasone), chloroquine, rifampicin or cimetidine
- •For children being breast fed, treatment of the mothers/wet nurses with PZQ in the 3 days prior to administration of Investigational medicinal product
- •Previous history of adverse reactions associated with PZQ treatment
- •Marked increases of the liver transaminases (alanine aminotransferase and/or aspartate aminotransferase) above 3x Upper Limit of Normal (ULN)
- •History of acute or severe chronic disease including hepato-splenic schistosomiasis
- •Fever defined as temperature above 38.0 degree centigrade
- •Debilitating illnesses such as tuberculosis, malnutrition, etc. as well as a medical history of seizures
- •Mixed S. haematobium and S. mansoni infections
- •Findings in the clinical examination of schistosome-infected children participating in the study as performed by the study clinician on the treatment day, that in the opinion of the Investigator constitutes a risk or a contraindication for the participation of the subject in the study or that could interfere with the study objectives, conduct or evaluation
- •Unlikelihood to comply with the protocol requirements, instructions and trial-related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial
研究组 & 干预措施
Part 1, Cohort 1: Biltricide (racemate praziquantel) 20 mg/kg
Participants received Biltricide (600 mg tablet) administered orally at a dose of 20 milligram per kilogram (mg/kg), three times a day on treatment Day 1.
干预措施: Biltricide (racemate praziquantel) oral tablets (Drug)
Part 1, Cohort 2: Biltricide (racemate praziquantel) 40 mg/kg
Participants received Biltricide (600 mg tablet) administered orally at a dose of 40 mg/kg as a single dose on treatment Day 1.
干预措施: Biltricide (racemate praziquantel) oral tablets (Drug)
Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg
Participants received Racemate Praziquantel oral dispersible tablet (ODT) (150 mg) administered orally at a dose of 40 mg/kg as a single dose on treatment Day 1.
干预措施: Racemate Praziquantel ODT (Drug)
Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg
Participants received Racemate Praziquantel ODT (150 mg) administered orally at a dose of 60 mg/kg as a single dose on treatment Day 1.
干预措施: Racemate Praziquantel ODT (Drug)
Part 1, Cohort 5: Levo Praziquantel 30 mg/kg
Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 30 mg/kg as a single dose on treatment Day 1.
干预措施: Levo Praziquantel ODT (Drug)
Part 1, Cohort 6: Levo Praziquantel 45 mg/kg
Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 45 mg/kg as a single dose on treatment Day 1.
干预措施: Levo Praziquantel ODT (Drug)
Part 1, Cohort 7: Levo Praziquantel 60 mg/kg
Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 60 mg/kg as a single dose on treatment Day 1.
干预措施: Levo Praziquantel ODT (Drug)
Part 2, Cohort 8: Levo Praziquantel 50 mg/kg
Participants aged 13-24 months months received Levo Praziquantel ODT (150 mg) administered orally at a dose of 50 mg/kg as a single dose on treatment day 1.
干预措施: Levo Praziquantel ODT (Drug)
Part 2, Cohort 9: Levo Praziquantel 50 mg/kg
Participants aged 3 to 12 months received Levo Praziquantel ODT (150 mg) administered orally at a dose of 50 mg/kg as a single dose on treatment day 1.
干预措施: Levo Praziquantel ODT (Drug)
结局指标
主要结局
Number of Participants With Clinical Cure Determined by Kato-Katz Method
时间窗: 14-21 days post treatment
Clinical cure was defined as zero egg counts at 14-21 days post treatment as determined by the Kato-Katz method. Number of participants with clinical cure were reported.
次要结局
- Number of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test(Day 2, Day 8 and 14-21 days post treatment)
- Egg Reduction Rate (Percent)(Baseline, 14-21 days post treatment)