Multiple Dose Study to Evaluate Security, Tolerance and Pharmacokinetic of Fexinidazole (Drug Candidate for Human African Trypanosomiasis) Administered With a Loading Dose and With Food

This study has been terminated.
(poor tolerability at highest dose)
Sponsor:
Information provided by (Responsible Party):
Drugs for Neglected Diseases
ClinicalTrials.gov Identifier:
NCT01483170
First received: November 29, 2011
Last updated: February 10, 2012
Last verified: February 2012
  Purpose

This trial will study the tolerability and pharmacokinetic of fexinidazole using two different dosage regimen of repeated administrations. The drug is administered to human healthy volunteers of sub-saharan origin together with food, once a day during 10 days, with a loading dose during 4 days.


Condition Intervention Phase
Trypanosomiasis, African
Drug: Tablets Fexinidazole
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-blind, Placebo Controlled, Randomized Multiple Ascending Dose Study in Fed Conditions for Ten Days Dosing Regimen With a Loading Dose to Evaluate the Safety, the Tolerability and the Pharmacokinetics of Oral Fexinidazole in 36 Healthy Male Sub-Saharan Volunteers.

Further study details as provided by Drugs for Neglected Diseases:

Enrollment: 30
Study Start Date: September 2011
Study Completion Date: February 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fexinidazole Drug: Tablets Fexinidazole
Administration of 3 or 4 tablets of 600mg per day during 4 days (loading dose) then administration of 2 tablets of 600mg for 6 days Dosing in fed condition.
Placebo Comparator: Placebo fexinidazole Drug: Placebo
Placebo fexinidazole

Detailed Description:

Objectives:

Primary Objectives: To assess safety and tolerability of two different fexinidazole dosing regimen, for 10 days repeated administration under fed conditions in healthy male sub-Saharan volunteers.

Secondary objectives: To validate the exposure to fexinidazole, M1 and M2 after different dosing regimens in fed conditions for 10 days in order to evaluate the more appropriate administration regimen for the pivotal phase II/III study.

Methodology/Study Design:

Two dose regimens consisting of repeated oral ascending dose (OAD) dosing in fed condition with two different ascending loading doses for 4 days followed by the same dose for 6 days will be evaluated. The study will be conducted in double-blind conditions for both the clinical and bioanalytical parts.

For each dosing regimen, subjects will reside at the clinical unit from the evening of Day -2 to the afternoon of Day 17 including an 8 days safety follow up (168 h post last dose).

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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 m)2 from 18 to 28 kg/m2 inclusive 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 10 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,
  • With any clinically significant abnormality following review of pre-study laboratory tests(ASAT, ALAT and alkaline phosphatase (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 (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.
  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: NCT01483170

Locations
France
SGS Life Sciences
Paris, France, 75015
Sponsors and Collaborators
Drugs for Neglected Diseases
Investigators
Principal Investigator: Lionel Hovsepian, MD SGS Aster
  More Information

Additional Information:
No publications provided

Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT01483170     History of Changes
Other Study ID Numbers: DNDiFEX003
Study First Received: November 29, 2011
Last Updated: February 10, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

ClinicalTrials.gov processed this record on October 22, 2014