Bioequivalence (BE) Study Comparing Fluconazole 150mg Capsule Manufactured in China and in France

NCT03621072 | Completed Phase 1 FDA Drug

• 1 other identifier: A0561025
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bioequivalence

Keywords

Fluconazole; Bioequivalence; Phase I; Chinese; Healthy Subjects

Outcome Measures

Primary Outcomes (2)

• AUC0-72

  Area under the plasma concentration-time profile from time zero to 72 hours post dose based on observed plasma concentrations at time points 0 (prior-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6,8, 10, 12, 24, 48 and 72 hours after dose using linear/log trapezoidal methods

  0-72 hours

• Cmax

  Maximum plasma concentration among observed plasma concentrations at time points 0 (prior-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6,8, 10, 12, 24, 48 and 72 hours after dose

  0-72hours

Secondary Outcomes (1)

• Adverse Events

  Day 1 to Day 18 or early termination, plus at least 28 calendar days and up to 35 calendar days after the last administration of the investigational product

Study Arms (2)

Reference

OTHER

Fluconazole 150mg Capsule Originator

Drug: Fluconazole 150mg Capsule Originator

Experimental

EXPERIMENTAL

Fluconazole 150mg Capsule Localized Originator

Drug: Fluconazole 150mg Capsule Localized Originator

Interventions

Fluconazole 150mg Capsule Originator DRUG

150mg fluconazole capsule (originator) manufactured at Pfizer Fareva, Amboise, France

Also known as: The originator, Reference

Reference

Fluconazole 150mg Capsule Localized Originator DRUG

150mg Fluconazole capsule (localized originator) manufactured at Pfizer, Dalian, China

Also known as: The localized originator, Experimental

Experimental

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Subjects must be of Chinese ethnicity (individuals currently residing in mainland China who were born in China and have both parents of Chinese descent)

You may not qualify if:

• 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).
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug screen.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Female subjects who are breastfeeding or with positive pregnancy test at Screening and during the study period.
• 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.
• Blood donation (excluding plasma donations) of approximately 400 mL or more within 60 days prior to dosing.
• History of sensitivity to heparin or heparin induced thrombocytopenia.
• History of hypersensitivity to fluconazole or any components of its formulation.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Wuxi People's Hospital//Phase One Unit

Wuxi, Jiangsu, 214023, China

Location

Related Publications (1)

• Chen N, He Q, Ma Y, Liu S, Wei H, Peng A. Pharmacokinetics and Bioequivalence of Fluconazole Capsules Manufactured in France and China in Healthy Chinese Participants: Open-Label, Randomized, Single-Dose, 2-Way, Crossover Bioequivalence Study Under Fasted and Fed Conditions. Clin Pharmacol Drug Dev. 2023 Jun;12(6):572-578. doi: 10.1002/cpdd.1248. Epub 2023 Apr 10.

  PMID: 37036155 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Fluconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 8, 2018
• Study Start: June 3, 2019
• Primary Completion: July 20, 2019
• Study Completion: July 20, 2019
• Last Updated: July 16, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)