Randomized, Double-blind, Placebo-controlled Study of the Tolerability, and Pharmacokinetics of Fexinidazole After Single and Repeated Oral Ascending Doses, Completed by a Comparative Bioavailability Study of an Oral Suspension Versus a Tablet and an Exploratory Assessment of Food Effect, in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- Occurence of adverse events (AEs)
研究概览
简要总结
This study is aimed at assessing the tolerability and pharmacokinetic parameters of the fexinidazole in healthy volunteers. In animal models of both acute and chronic experimental Trypanosomiasis infections, fexinidazole shows highly promising efficacy.
详细描述
The present study is designed to obtain safety, tolerability and PK data after single and multiple oral administration of increasing doses of fexinidazole in healthy male sub-Saharan African subjects. This study will also assess the relative bioavailability of fexinidazole administered as a tablet in comparison with oral suspension, and to assess the impact of concomitant food intake on the relative bioavailability of fexinidazole after single oral dose administration.
The study will be divided in 3 successive parts. Study Part I will be a randomized, double-blind, placebo-controlled, single ascending dose study with fexinidazole administered as an oral suspension.
Study Part II will be a comparative bioavailability study of a fexinidazole tablet vs. the oral suspension and assessment of food effect, according to a three-way cross-over design. Clinical part will be conducted in open conditions and bioanalysis in blind conditions.
Study Part III will be a randomized, double-blind, placebo-controlled, multiple ascending dose study with fexinidazole administered either as an oral suspension or as a tablet, depending on Part II results. Dosage regimen will be either q.d. or b.i.d., depending on Part I and Part II results for the unchanged drug and the metabolites. Treatment duration will be 14 days.
Bioanalysis will be performed in open conditions for Study Part I and Study Part III.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •All subjects to be of sub-Saharan African origins with both parents of sub-Saharan African origins too,
- •Male subjects with a body mass index (BMI) calculated as weight in kg/(height in m2) from 18 to 28 kg/m2 at screening,
- •Able to communicate well with the Investigator and research staff and to comply with the requirements of the entire study,
- •Provision of written informed consent to participate as shown by a signature on the volunteer consent form,
- •Light smokers (less than 5 cigarettes per day) or subjects who are non-smokers.
- •Normal arterial blood pressure (BP) and pulse rate or, if abnormal, considered not clinically significant by the principal Investigator.
- •Registered with the French Social Security in agreement with the French law on biomedical experimentation.
排除标准
- •Who on direct questioning and physical examination have evidence of any clinically significant acute or chronic disease, including known or suspected HIV, HBV or HCV infection,
- •Who previously received fexinidazole,
- •With any clinically significant abnormality following review of pre-study laboratory tests(ASAT, ALAT and ALP must be within normal ranges), vital signs, full physical examination and ECG,
- •Who are within the exclusion period defined in the National Register for Healthy Volunteers of the French Ministry of Health,
- •Who forfeit their freedom by administrative or legal award or who were under guardianship,
- •Unwilling to give their informed consent,
- •Who have a positive laboratory test for Hepatitis B surface antigen (HbsAg), or anti-HIV 1/2 or anti- HCV antibodies
- •Who have a history of allergy, intolerance or photosensitivity to any drug,
- •Who have a history of serious allergy, asthma, allergic skin rash or sensitivity to any drug,
- •Who are known or suspected alcohol or drug abusers (more than 14 units of alcohol per week, one unit = 8 g or about 10 mL of pure alcohol),
- •Who drink more than 8 cups daily of beverage containing caffeine,
- •Who have a positive laboratory test for urine drug screening
- •Who have undergone surgery or have donated blood within 12 weeks prior to the start of the study,
- •Who have taken any prescribed or over the counter drug (including antacid drug), with the exception of paracetamol (up to 3 g per day) within 2 weeks prior to the first dose administration,
- •Who have any clinical condition or prior therapy which, in the opinion of the Investigator, made the subject unsuitable for the study,
- •Who participated to any clinical trial with an investigational drug in the past 3 months preceding study entry.
研究组 & 干预措施
Fexinidazole
干预措施: Fexinidazole/Placebo (Drug)
Placebo
干预措施: Fexinidazole/Placebo (Drug)
结局指标
主要结局
Occurence of adverse events (AEs)
时间窗: 8 to 37 days, depending on the part of the study
次要结局
- Pharmacokinetic : measure of blood and urine concentration of fexinidazole, fexinidazole sulfoxide and fexinidazole sulfone in order to determine AUC0-t and Cmax values, for all dose levels(pre-dose, and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120, 144 and 168 h post-dose)