human african trypanosomiasis: first in man clinical trial of a new medicinal product, the scyx-7158

Conditions: Trypanosomiasis; Trypanosomiasis, African; Protozoan Infections; Parasitic Diseases

Summary: this study is aimed at assessing the tolerability and pharmacokinetic parameters of scyx-7158 in healthy volunteers. in animal models of both acute and chronic experimental trypanosomiasis infections, scyx-7158 shows highly promising efficacy.

the present study is designed to obtain safety, tolerability and pk data after single oral administration of increasing doses of scyx-7158 in healthy male sub-saharan african subjects. this study will also assess the impact on the relative bioavailability of scyx-7158 administered as a capsule after single oral dose administration. the study will be divided in 3 different parts. study part i will be a randomized, double-blind, placebo-controlled, single ascending dose study with scyx-7158 administered as a capsule. a other part is scheduled to evaluate the impact of activated charcoal intake on the pk characteristics of scyx-7158 and determine the most adapted treatment schedule for charcoal to enhance scyx-7158 elimination while allowing a sustained drug exposure likely to be therapeutically active. a last part is planned to evaluate the pharmacokinetics of a new formulation (tablet) of scyx-7158 in healthy male volunteers

Eligibility criteria:
inclusion criteria: * male healthy volunteers 18 to 45 years of age, * 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. no smoking (or use of smoking substitute e.g. nicotine patch) is permitted from screening throughout the study, * normal arterial blood pressure (bp) and pulse rate or, if abnormal, considered not clinically significant by the principal investigator. these will be measured after resting for 5 min. * registered with the french social security in agreement with the french law on biomedical experimentation. exclusion criteria: * 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 scyx-7158, * who presented acute or chronic or history of symptoms of gastro intestinal disturbances (gi) or on physical examination have evidence of any clinical signs of acute or chronic gi abnormality ( i.e hemorrhoids, gi bleeding...) * with any clinically significant abnormality following review of pre-study laboratory tests (aspartate aminotransferase (asat) and alanine aminotransferase (alat) 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 (opiates, cocaine, amphetamine, cannabis, benzodiazepines), * 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.

Keywords: neglected disease africa new drug oral drug parasite