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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

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ClinicalTrials.gov Identifier: NCT03918551
Recruitment Status : Completed
First Posted : April 17, 2019
Last Update Posted : July 8, 2019
Sponsor:
Collaborator:
Altasciences Company Inc.
Information provided by (Responsible Party):
Pharmtechnology LLC

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.

Condition or disease Intervention/treatment Phase
Bioequivalence Drug: Febuxostat Drug: Adenuric Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Other
Official Title: Single Dose Crossover Comparative Bioavailability Study of Febuxostat 120 mg Film-Coated Tablets in Healthy Adult Subjects / Fasting State
Actual Study Start Date : May 3, 2019
Actual Primary Completion Date : June 6, 2019
Actual Study Completion Date : June 6, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Febuxostat

Arm Intervention/treatment
Sequence AB
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
Febuxostat is manufactured by Pharmtechnology LLC, Republic of Belarus. Each film-coated tablet contains 120 mg of febuxostat.
Other Name: the test product

Drug: Adenuric
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.
Other Name: the reference product

Sequence BA
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
Febuxostat is manufactured by Pharmtechnology LLC, Republic of Belarus. Each film-coated tablet contains 120 mg of febuxostat.
Other Name: the test product

Drug: Adenuric
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.
Other Name: the reference product




Primary Outcome Measures :
  1. Cmax of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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 ]
    Maximum observed concentration in plasma

  2. AUC0-T of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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 ]
    Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method


Secondary Outcome Measures :
  1. Tmax of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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 of maximum observed concentration; if it occurs at more than one time point, Tmax is defined as the first time point with this value

  2. TLQC of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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 of last observed quantifiable concentration

  3. AUC0-∞ of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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 ]
    Area under the concentration time curve extrapolated to infinity, calculated as AUC0-T + ĈLQC (the predicted concentration at time TLQC) / λZ (apparent elimination rate constant)

  4. Residual area of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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 ]
    Extrapolated area (i.e. percentage of AUC0-∞ due to extrapolation from TLQC to infinity)

  5. Time point where the log-linear elimination phase begins (TLIN) of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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

  6. λZ of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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 ]
    Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus time curve

  7. Terminal elimination half-life (Thalf) of febuxostat in plasma after administration of the test and the reference products [ Time Frame: 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 ]
    Terminal elimination half-life, calculated as ln(2)/λZ

  8. Number of treatment-emergent adverse events for the test and the reference products [ Time Frame: Up to 9 days (after the first drug administration until the completion of clinical part of the study)] ]
    The safety population will include all subjects who received at least one dose of the test or the reference product. Any significant changes will be recorded as treatment-emergent adverse events only if they are judged clinically significant by the qualified investigator or delegate.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Provision of signed and dated informed consent form (ICF)
  2. Stated willingness to comply with all study procedures and availability for the duration of the study
  3. Healthy male or female adult volunteer
  4. A female volunteer meeting one of the following criteria:

    1. 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

      Or

    2. 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

      Or

    3. 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)
  5. Volunteer aged at least 18 years
  6. Volunteer with a body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
  7. 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
  8. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without clinical significance, as determined by an investigator
  9. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an investigator

Exclusion Criteria:

  1. Females who are lactating at screening
  2. Females who are pregnant according to the pregnancy test at screening or prior to the first study drug administration
  3. 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
  4. 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
  5. History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
  6. History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
  7. Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment
  8. History of rare hereditary problems of galactose and/or lactose intolerance, lactase deficiency or glucose-galactose malabsorption
  9. 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)
  10. Any clinically significant illness in the 28 days prior to the first study drug administration
  11. 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
  12. Any history of tuberculosis
  13. Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration
  14. Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or Hepatitis C Virus (HCV (C)) tests
  15. Volunteers who have already been included in a previous group for this clinical study
  16. Volunteers who took febuxostat in the 28 days prior to the first study drug administration
  17. Volunteers who took an Investigational Product (IP) in the 28 days prior to the first study drug administration
  18. Volunteers who donated 50 mL or more of blood in the 28 days prior to the first study drug administration
  19. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03918551


Locations
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Canada, Quebec
Altasciences Company Inc.
Montréal, Quebec, Canada, H3P 3P1
Sponsors and Collaborators
Pharmtechnology LLC
Altasciences Company Inc.
Investigators
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Principal Investigator: Eric Sicard, MD Altasciences Company Inc.

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Responsible Party: Pharmtechnology LLC
ClinicalTrials.gov Identifier: NCT03918551     History of Changes
Other Study ID Numbers: PTL-P1-099 (v. 1.0 03/15/2019)
First Posted: April 17, 2019    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pharmtechnology LLC:
bioequivalence
febuxostat
Adenuric
Additional relevant MeSH terms:
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Febuxostat
Gout Suppressants
Antirheumatic Agents