Human African Trypanosomiasis: First in Man Clinical Trial of a New Medicinal Product, the SCYX-7158

• Pharmacokinetic (blood concentration of SCYX-7158 and metabolite) [ Time Frame: from pre-dose until 168 h post-dose. ] [ Designated as safety issue: No ]
• Pharmacokinetic (urine concentration of SCYX-7158 and metabolite) [ Time Frame: from pre-dose until 168 h post-dose. ] [ Designated as safety issue: No ]

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 and multiple oral administration of increasing doses of SCYX-7158 in healthy male sub-Saharan African subjects. This study will also assess the impact of concomitant food intake on the relative bioavailability of SCYX-7158 administered as a capsule 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 SCYX-7158 administered as a capsule.

Study Part II will be a comparative bioavailability study of SCYX-7158 capsule administered in fasting or fed condition (assessment of food effect), according to a two-way cross-over design (or three ways depending on results). 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 SCYX-7158 administered as a capsule. 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 metabolite. Treatment duration will be 15 days, including placebo on day-1.

Bioanalysis will be performed in open conditions for Study Part I and Study Part III.

• Trypanosomiasis
• Trypanosomiasis, African
• Protozoan Infections
• Parasitic Diseases

• Drug: SCYX-7158
• Drug: Placebo

• Experimental: SCYX-7158
  Intervention: Drug: SCYX-7158
• Placebo Comparator: Placebo of SCYX-7158
  Intervention: Drug: Placebo

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.