Bioequivalence Study - Reference Clinical Fexinidazole Tablet Versus Proposed Market Formulation
Condition: Trypanosomiasis, African
MeSH terms: Trypanosomiasis; Trypanosomiasis, African
Study type: Interventional
Phase: Phase 1

Summary: 
      Phase 1 bioequivalence (BE) study. This study is for regulatory purpose to determine BE of
      the tablet formulation used in the clinical trials and the final marketed tablet formulation
      under fed condition.

      The study will be an open-label, 2-treatment, 2-sequence, 4-period, single-dose, replicate
      crossover study under fed condition. The 4-period sequences for the replicate design will be
      TRTR and RTRT, where R designates the reference formulation and T the test formulation.
      Subject will be allocated randomly to one of the two sequences of treatments according to the
      randomization list.
    

Detailed description: 
      Ideally, BE study should be conducted under fasting condition as this is considered to be the
      most sensitive condition to detect a potential difference between formulations. However as
      fexinidazole is recommended to be taken with food, as food increased the plasma concentration
      by 2.5 to 3 fold compared to plasma. BE will be conducted under fed condition, using field
      adapted meal. The wash-out period should be sufficient to ensure that drug concentrations are
      below the limit of quantification in all the subjects at the beginning of the next period, a
      2 weeks wash-out period will be used. The intra-subject variability of fexinidazole was
      evaluated based on a previous 3-period cross-over study (1) and was estimated at 25%. As this
      value was quite high and close to 30%, a replicate design was chosen.

      Primary objective:

      To assess BE of the clinical trial 600 mg tablet formulation versus (vs.) the proposed market
      600 mg tablet formulation of fexinidazole under fed condition after single oral
      administration of 1200 mg.

      Secondary objectives:

      To assess the pharmacokinetic profile of the two metabolites fexinidazole sulfoxide and
      fexinidazole sulfone under the fed condition. To assess the safety and tolerability in
      healthy volunteers under the same study conditions.

      Meal: On each treatment period, fexinidazole will be given with concomitant meal which
      composition will be as close as possible to field condition

      sample size: In order to have 24 evaluable subjects a total of 30 subjects will be recruited
      in the study.

      Study Treatment: Single oral dose of 1200 mg / period :

        -  Treatment R: Reference formulation, i.e. 2 × 600 mg clinical tablets

        -  Treatment T: Test formulation, i.e. 2 × 600 mg proposed market tablets

      Pharmacokinetic sampling: Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 120 and 168
      h post-dose Total blood drawn: 390 mL ( Pharmacokinetic = 240 mL + safety = 150 mL)
    

Intervention name(s): Fexinidazole
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Keywords: bioequivalence