Bioequivalence Study of Two Formulations of Febuxostat 120 mg Film-coated Tablets in Healthy Adult Volunteers After a Single Oral Dose Administration Under Fasting Conditions

NCT03918551 | Completed Phase 1

• 1 other identifier: PTL-P1-099 (v. 1.0 03/15/2019)
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed in accordance with the European Medicines Agency (EMA) regulatory guidelines, with the aim of characterizing the bioavailability of febuxostat in the two formulations in healthy adult subjects. Within the clinical portion of the study each subject will receive a single oral dose of the test and the reference formulation in compliance with the generated randomization code. The primary study endpoints are the pharmacokinetic (PK) parameters Cmax and AUC0-T of febuxostat.

Conditions

Bioequivalence

Keywords

bioequivalence; febuxostat; Adenuric

Outcome Measures

Primary Outcomes (2)

• Cmax of febuxostat in plasma after administration of the test and the reference products

  Maximum observed concentration in plasma

  Time points 0.00 (prior to each drug administration) and 0.25, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 18.00, 24.00, 36.00 hours after each drug administration

• AUC0-T of febuxostat in plasma after administration of the test and the reference products

  Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method

  Time points 0.00 (prior to each drug administration) and 0.25, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 18.00, 24.00, 36.00 hours after each drug administration

Secondary Outcomes (8)

• Tmax of febuxostat in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.25, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 18.00, 24.00, 36.00 hours after each drug administration

• TLQC of febuxostat in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.25, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 18.00, 24.00, 36.00 hours after each drug administration

• AUC0-∞ of febuxostat in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.25, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 18.00, 24.00, 36.00 hours after each drug administration

• Residual area of febuxostat in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.25, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 18.00, 24.00, 36.00 hours after each drug administration

• Time point where the log-linear elimination phase begins (TLIN) of febuxostat in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.25, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 18.00, 24.00, 36.00 hours after each drug administration

Study Arms (2)

Sequence AB

OTHER

25 subjects assigned to the sequence AB will receive a single 120 mg dose of the test product Febuxostat (1 x 120 mg film-coated tablet), marked as A in the sequence, in Period 1 and a single 120 mg dose of the reference product Adenuric (1 x 120 mg film-coated tablet), marked as B in the sequence, in period 2. These treatments will be administered orally with approximately 240 mL of water at ambient temperature, in the morning, following a minimum of 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Febuxostat; Drug: Adenuric

Sequence BA

OTHER

25 subjects assigned to the sequence BA will receive a single 120 mg dose of the reference product Adenuric (1 x 120 mg film-coated tablet), marked as B in the sequence, in Period 1 and a single 120 mg dose of the test product Febuxostat (1 x 120 mg film-coated tablet), marked as A in the sequence, in period 2. These treatments will be administered orally with approximately 240 mL of water at ambient temperature, in the morning, following a minimum of 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Febuxostat; Drug: Adenuric

Interventions

Febuxostat DRUG

Febuxostat is manufactured by Pharmtechnology LLC, Republic of Belarus. Each film-coated tablet contains 120 mg of febuxostat.

Also known as: the test product

Sequence AB; Sequence BA

Adenuric DRUG

Adenuric is manufactured by Menarini - Von Heyden GmbH, Germany (MAH: Menarini International Operations Luxembourg S.A., Luxembourg). Each film-coated tablet contains 120 mg of febuxostat.

Also known as: the reference product

Sequence AB; Sequence BA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form (ICF)
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Healthy male or female adult volunteer
• A female volunteer meeting one of the following criteria:
• Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the first study drug administration through to at least 30 days after the last dose of the study drug. An acceptable method of contraception includes one of the following:
• Abstinence from heterosexual intercourse
• Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)
• Intrauterine device (IUD) (with or without hormones)
• Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository)
• Male partner vasectomized at least 6 months prior to the first study drug administration
• Participant whose partner has had a vasectomy less than 6 months prior to dosing, and agrees to use an additional acceptable method of contraception from the first study drug administration through to at least 30 days after the last dose of the study drug
• Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a postmenopausal state (i.e. at least 1 year without menses without an alternative medical condition prior to the first study drug administration)
• Volunteer aged at least 18 years
• Volunteer with a body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
• Non- or ex-smoker; an ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration

You may not qualify if:

• Females who are lactating at screening
• Females who are pregnant according to the pregnancy test at screening or prior to the first study drug administration
• History of significant hypersensitivity to febuxostat or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence of significant gastrointestinal, liver or kidney disease, or any other condition known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects
• History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
• History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
• Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment
• History of rare hereditary problems of galactose and/or lactose intolerance, lactase deficiency or glucose-galactose malabsorption
• Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the 28 days prior to the first study drug administration
• Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of an investigator would put into question the status of the volunteer as healthy
• Any history of tuberculosis
• Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration
• Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or Hepatitis C Virus (HCV (C)) tests
• Volunteers who have already been included in a previous group for this clinical study

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• Altasciences Company Inc.: collaborator

Study Sites (1)

Altasciences Company Inc.

Montreal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Interventions

Febuxostat

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Eric Sicard, MD

  Altasciences Company Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The randomization code will not be available to the personnel of the bioanalytical facility until the bioanalytical tables have been finalized and audited by the Quality Assurance (QA) department.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 17, 2019
• Study Start: May 3, 2019
• Primary Completion: June 6, 2019
• Study Completion: June 6, 2019
• Last Updated: July 8, 2019

Record last verified: 2019-04

Locations

CA (1)