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

Brief Title

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

Official Title

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

Brief Summary

      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.
    

Detailed Description

      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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Occurence of adverse events (AEs)

Secondary Outcome

 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

Condition

Human African Trypanosomiasis

Intervention

Fexinidazole/Placebo

Study Arms / Comparison Groups

 Fexinidazole
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

108

Start Date

September 2009

Completion Date

October 2010

Primary Completion Date

September 2010

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        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 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.
      

Gender

Male

Ages

18 Years - 45 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Lionel Hovsepian, MD, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT00982904

Organization ID

DNDiFEX001


Responsible Party

Sponsor

Study Sponsor

Drugs for Neglected Diseases

Collaborators

 Sanofi

Study Sponsor

Lionel Hovsepian, MD, Principal Investigator, SGS Aster


Verification Date

April 2017