Clinical trial NCT01533961: Human African Trypanosomiasis: First in Man Clinical Trial of a New Medicinal Product, the SCYX-7158
Official title: Randomized, Double-blind, Placebo-controlled Sequential Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SCYX-7158 After Single Oral Ascending Doses in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Trypanosomiasis
Trypanosomiasis, African
Protozoan Infections
Parasitic Diseases
Keywords: neglected disease
africa
new drug
oral drug
parasite
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
First posted: 2012-02-16
Enrollment: 136
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Occurence of adverse events (AEs)
timeFrame: 9 to 37 days, depending on the part of the study
Secondary outcomes:
measure: Pharmacokinetic (blood concentration of SCYX-7158 and metabolite)
timeFrame: from pre-dose until 168 h post-dose.
measure: Pharmacokinetic (urine concentration of SCYX-7158 and metabolite)
timeFrame: from pre-dose until 168 h post-dose.
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Optimed
city: Paris
country: France
facility: SGS Aster
Study officials:
affiliation: Drugs for Neglected Diseases initiative
name: Antoine Tarral, MD
role: STUDY_DIRECTOR
References: