Bioequivalence (BE) Study Comparing Fluconazole 150mg Capsule Manufactured in China and in France
Condition: Bioequivalence
Study type: Interventional
Phase: Phase 1

Summary: 
      China Food and Drug Administration (CFDA) initiated a generic consistency evaluation program
      to evaluate the quality and efficacy of the products manufactured in China in 2016. This is a
      bioequivalence study to support the program and to demonstrate the bioequivalence between the
      150 mg fluconazole capsule manufactured at Pfizer Dalian, China (the localized originator,
      Test) and the 150 mg fluconazole capsule manufactured at Pfizer Fareva, Amboise, France (the
      originator, Reference) in healthy Chinese subjects under fasted and fed conditions. This
      open-lable, randomized, single-dose 2-way crossover study will enroll approximately 18
      subjects for each condition. The primary endpoints are fluconazole area under the plasma
      concentration-time curve from time zero to 72 hours post-dose (AUC72) and Cmax.
    

Detailed description: 
      This trial is a bioequivalence study to support a generic consistency evaluation program,
      initiated by the China Food and Drug Administration (CFDA), for the evaluation of quality and
      efficacy of the products manufactured in China. The selected strength of 150 mg capsule is
      the approved highest strength of capsule formulation in China. The 150 mg dose was selected
      for evaluation in this study as it is one of the commonly used clinically approved doses. The
      primary objective is to demonstrate the bioequivalence between the 150 mg fluconazole capsule
      manufactured at Pfizer Dalian, China (the localized originator, Test) and the 150 mg
      fluconazole capsule manufactured at Pfizer Fareva, Amboise, France (the originator,
      Reference) administered as a single oral dose in healthy Chinese subjects under fasted and
      fed conditions. The primary endpoints are fluconazole area under the plasma
      concentration-time curve from time zero to 72 hours post-dose (AUC72) and peak plasma
      concentrations (Cmax).

      The secondary objective is to evaluate the safety and tolerability of fluconazole
      administered as a single oral dose of 150 mg capsule manufactured at Pfizer Dalian, China and
      150 mg capsule manufactured at Pfizer Fareva, Amboise, France in healthy Chinese subjects
      under fasted and fed conditions. The secondary endpoint is adverse events (AEs). Other
      endpoints include time to reach Cmax (Tmax) of fluconazole, safety laboratory tests and vital
      signs.

      In each group, subjects will be randomized to one of the 2 treatment sequences. Each
      treatment sequence will consist of 2 periods, separated by a washout period of at least 14
      days between each period.

      On Day 1 of each period in both groups, each subject will be administered investigational
      product at approximately 8:00 AM (± 2 hours). Blood samples for the analysis of fluconazole
      in plasma will be collected at pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 1,
      1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48 and 72 hours post dose in each period. Vital signs,
      physical examination, laboratory tests and 12 lead electrocardiogram (ECG) will be performed
      at specified times. Tolerability and safety will be assessed for all treatments by monitoring
      AEs.
    

Intervention name(s): Fluconazole 150mg Capsule Originator; Fluconazole 150mg Capsule Localized Originator
Intervention type(s): Drug; Drug
Intervention description(s): 150mg fluconazole capsule (originator) manufactured at Pfizer Fareva, Amboise, France; 150mg Fluconazole capsule (localized originator) manufactured at Pfizer, Dalian, China
Other intervention name(s): The originator, Reference; The localized originator, Experimental
Intervention MeSH terms: Fluconazole
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is an open-label, randomized, single-dose, 2-way crossover bioequivalence study under fasted and fed conditions in healthy Chinese subjects. Under each condition, subjects will be randomized to one of the 2 treatment sequences. Each treatment sequence will consist of 2 periods, separated by a washout period of at least 14 days between each period. For sequence 1, first localized originator and then originator will be administered. The order for sequence 2 is originator and localized originator.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Fluconazole; Bioequivalence; Phase I; Chinese; Healthy Subjects