Bioequivalence Study - Reference Clinical Fexinidazole Tablet Versus Proposed Market Formulation

Trypanosomiasis, African Clinical Trial

Official title: A Bioequivalence Study of the Reference Clinical Fexinidazole Tablet vs Proposed Market Formulation in Healthy Male Volunteers of African Sub-Saharan Origin:an Open-label,Randomized,Two-treatment,Single Dose,Replicate Design,Fed Condition

Status Completed

Clinical Trial 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.

Clinical Trial 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) ;

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Trypanosomiasis
• Trypanosomiasis, African

• NCT number: NCT02571062
• Study type: Interventional
• Source: Drugs for Neglected Diseases
• Status: Completed
• Phase: Phase 1
• Start date: March 2015
• Completion date: June 2015