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

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by:
Drugs for Neglected Diseases
ClinicalTrials.gov Identifier:
NCT00982904
First received: September 22, 2009
Last updated: March 9, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Human African Trypanosomiasis
Drug: Fexinidazole/Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Further study details as provided by Drugs for Neglected Diseases:

Primary Outcome Measures:
  • Occurence of adverse events (AEs) [ Time Frame: 8 to 37 days, depending on the part of the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: pre-dose, and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120, 144 and 168 h post-dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 108
Study Start Date: September 2009
Study Completion Date: October 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fexinidazole Drug: Fexinidazole/Placebo
Placebo Comparator: Placebo Drug: Fexinidazole/Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00982904

Locations
France
SGS Aster
Paris, France, 75015
Sponsors and Collaborators
Drugs for Neglected Diseases
Sanofi
Investigators
Principal Investigator: Lionel Hovsepian, MD SGS Aster
Study Chair: Nathalie Strub-Wourgaft, MD Drugs for Neglected Diseases initiative
  More Information

Additional Information:
No publications provided

Responsible Party: Nathalie Strub-Wourgaft, Drugs for Neglected Diseases Initiative
ClinicalTrials.gov Identifier: NCT00982904     History of Changes
Other Study ID Numbers: DNDiFEX001
Study First Received: September 22, 2009
Last Updated: March 9, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Drugs for Neglected Diseases:
neglected disease
africa
new drug
oral drug
parasite

Additional relevant MeSH terms:
Trypanosomiasis, African
Trypanosomiasis
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on October 19, 2014