Bioequivalence (BE) Study Comparing Fluconazole 150mg Capsule Manufactured in China and in France
Bioequivalence (BE) Study Comparing Fluconazole 150mg Capsule Manufactured in China and in France
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.
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.
Inclusion Criteria:

 1. Healthy Chinese male and female subjects, between the ages of 18 and 55 years,
 inclusive. Healthy is defined as no clinically relevant abnormalities identified by a
 detailed medical history, full physical examination, including blood pressure (BP) and
 pulse rate (PR) measurement, 12-lead ECG, or clinical laboratory tests.

 2. Body Mass Index (BMI) of 18 to 28 kg/m**2, inclusive; and a total body weight >=50 kg
 for males and >= 45 kg for females.

 3. Evidence of a personally signed and dated informed consent document indicating that
 the subject has been informed of all pertinent aspects of the study.

 4. Subjects who are willing and able to comply with all scheduled visits, treatment plan,
 laboratory tests, and other study procedures.

 5. Subjects must be of Chinese ethnicity (individuals currently residing in mainland
 China who were born in China and have both parents of Chinese descent)

 Exclusion Criteria:

 1. Evidence or history of clinically significant hematological, renal, endocrine,
 pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
 allergic disease (including drug allergies, but excluding untreated, asymptomatic,
 seasonal allergies at the time of dosing).

 2. Any condition possibly affecting drug absorption (eg, gastrectomy).

 3. A positive urine drug screen.

 4. History of regular alcohol consumption exceeding 7 drinks/week for female subjects or
 14 drinks/week for male subjects (1 drink = 150 mL of wine or 360 mL of beer or (45 mL
 of hard liquor) within 6 months of Screening.

 5. Use of tobacco- or nicotine-containing products in excess of the equivalent of 5
 cigarettes per day within 3 months of Screening; a positive urine nicotine test.

 6. Treatment with an investigational drug (which has not been approved for registration)
 within 30 days preceding the first dose of investigational product. If the
 investigational drug has a long elimination half-life, the washout period will be
 longer with a recommendation of five elimination half-lives.

 7. Screening BP >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), following at least 5
 minutes of rest. If BP is >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), the BP
 should be repeated 2 more times and the average of the 3 BP values should be used to
 determine the subject's eligibility.

 8. Screening supine 12 lead ECG demonstrating a corrected QT (QTc) interval >450 msec or
 a QRS complex >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG
 should be repeated 2 more times and the average of the 3 QTc or QRS values should be
 used to determine the subject's eligibility.

 9. Female subjects of childbearing potential and fertile male subjects who are unwilling
 or unable to use a highly effective method of contraception as outlined in this
 protocol for the duration of the study and for at least 28 days after the last dose of
 investigational product.

 10. Female subjects who are breastfeeding or with positive pregnancy test at Screening and
 during the study period.

 11. Use of prescription or nonprescription drugs and dietary supplements within 7 days
 prior to the first dose of investigational product. If the concomitant medication has
 a long elimination half-life, the washout period will be longer with a recommendation
 of five elimination half-lives. As an exception, acetaminophen/paracetamol may be used
 at doses of <=1 g/day. Limited use of nonprescription medications that are not
 believed to affect subject safety or the overall results of the study may be permitted
 on a case by case basis following approval by the sponsor.

 12. Blood donation (excluding plasma donations) of approximately 400 mL or more within 60
 days prior to dosing.

 13. History of sensitivity to heparin or heparin induced thrombocytopenia.

 14. History of hypersensitivity to fluconazole or any components of its formulation.

 15. History of hepatitis B or hepatitis C; positive testing for hepatitis B surface
 antigen (HepBsAg), hepatitis B core antibody (HepBcAb), hepatitis C antibody (HCVAb),
 treponema pallidum antibody (TPPA) or human immunodeficiency virus (HIV) antibody.

 16. Unwilling or unable to comply with the criteria in the Lifestyle Guidelines described
 in this protocol.

 17. Subjects who are investigator site staff members directly involved in the conduct of
 the study and their family members, site staff members otherwise supervised by the
 investigator, or subjects who are Pfizer employees, including their family members,
 directly involved in the conduct of the study.

 18. Other acute or chronic medical or psychiatric condition including recent (within the
 past year) or active suicidal ideation or behavior or laboratory abnormality that may
 increase the risk associated with study participation or investigational product
 administration or may interfere with the interpretation of study results and, in the
 judgment of the investigator, would make the subject inappropriate for entry into this
 study.