Phase 1, Febuxostat XR Relative Bioavailability Study

Study Overview
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Brief Summary
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This study will assess the relative bioavailability, safety and tolerability following administration of 80 mg single oral doses of 4 febuxostat extended release (XR) formulations.

Detailed Description
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The drug being tested is this study is febuxostat XR. Four different formulations of febuxostat XR are being tested to see how the drug moves through the body. This study will look at safety and side effects in people who take febuxostat XR. This cross-over study will enroll approximately 78 patients. Participants will be randomly assigned to 1of 4 sequences which will determine the order of the 4 treatments received: Febuxostat XR 80 mg capsule Formulation 1 Febuxostat XR 80 mg capsule Formulation 2 Febuxostat XR 80 mg capsule Formulation 3 Febuxostat XR 80 mg capsule Formulation 4 Participants will take 1 dose on Day 1 with a washout period between each period. This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 80 days. Participants will make multiple visits to the clinic including a period of confinement, and will be contacted by telephone 30 days after last dose of study drug for a follow-up assessment.

Official Title
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A Phase 1, Randomized, Open-Label, Single-Dose, 4-Way Crossover Study to Assess the Relative Bioavailability of Four 80 mg Febuxostat XR Formulations

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Febuxostat XR 80 mg Capsule F1
* Drug: Febuxostat XR 80 mg Capsule F2
* Drug: Febuxostat XR 80 mg Capsule F3
* Drug: Febuxostat XR 80 mg Capsule F4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations. Is a healthy male or female and aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose. Weighs at least 50.0 kg and has a body mass index (BMI) from 18.0 to 30.0 kg/m2, inclusive at Screening. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent, Is willing to refrain from strenuous exercise from Day -1 of Period 1 until Study Exit (Day 3 of Period 4). Has estimated glomerular filtration rate (eGFR) ≥90 mL/min at Screening and Check-in (Day -1 of Period 1). Exclusion Criteria: Has received any investigational compound within 30 days prior to the first dose of study medication. Has received febuxostat in a previous clinical study or as a therapeutic agent. Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in the conduct of this study. Has uncontrolled, clinically significant (CS) disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results. Has a known hypersensitivity to any component of the formulation of XO inhibitors, xanthine compounds, caffeine, or any component of the formulation of febuxostat capsules.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence ABDC<br>Febuxostat XR 80 mg capsule Formulation 1 (F1), orally, once on Day 1 of Period 1 (A), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule Formulation 2 (F2), orally, once on Day 1 of Period 2 (B), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule Formulation 4 (F4), orally, once on Day 1 of Period 3 (D), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule Formulation 3 (F3), orally, once on Day 1 of Period 4 (C). | Drug: Febuxostat XR 80 mg Capsule F1<br>* Febuxostat extended-release (XR) capsules formulation 1<br>Drug: Febuxostat XR 80 mg Capsule F2<br>* Febuxostat XR capsules formulation 2<br>Drug: Febuxostat XR 80 mg Capsule F3<br>* Febuxostat XR capsules formulation 3<br>Drug: Febuxostat XR 80 mg Capsule F4<br>* Febuxostat XR capsules formulation 4<br>|
| Experimental: Treatment Sequence DACB<br>Febuxostat XR 80 mg capsule F4, orally, once on Day 1 of Period 1 (D), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F1 orally, once on Day 1 of Period 2 (A), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F3, orally, once on Day 1 of Period 3 (C), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F2, orally, once on Day 1 of Period 4 (B). | Drug: Febuxostat XR 80 mg Capsule F1<br>* Febuxostat extended-release (XR) capsules formulation 1<br>Drug: Febuxostat XR 80 mg Capsule F2<br>* Febuxostat XR capsules formulation 2<br>Drug: Febuxostat XR 80 mg Capsule F3<br>* Febuxostat XR capsules formulation 3<br>Drug: Febuxostat XR 80 mg Capsule F4<br>* Febuxostat XR capsules formulation 4<br>|
| Experimental: Treatment Sequence CDBA<br>Febuxostat XR 80 mg capsule F3, orally, once on Day 1 of Period 1 (C), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F4 orally, once on Day 1 of Period 2 (D), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F2, orally, once on Day 1 of Period 3 (B), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F1, orally, once on Day 1 of Period 4 (A). | Drug: Febuxostat XR 80 mg Capsule F1<br>* Febuxostat extended-release (XR) capsules formulation 1<br>Drug: Febuxostat XR 80 mg Capsule F2<br>* Febuxostat XR capsules formulation 2<br>Drug: Febuxostat XR 80 mg Capsule F3<br>* Febuxostat XR capsules formulation 3<br>Drug: Febuxostat XR 80 mg Capsule F4<br>* Febuxostat XR capsules formulation 4<br>|
| Experimental: Treatment Sequence BCAD<br>Febuxostat XR 80 mg capsule F2, orally, once on Day 1 of Period 1 (B), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F3 orally, once on Day 1 of Period 2 (C), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F1, orally, once on Day 1 of Period 3 (A), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F4, orally, once on Day 1 of Period 4 (D). | Drug: Febuxostat XR 80 mg Capsule F1<br>* Febuxostat extended-release (XR) capsules formulation 1<br>Drug: Febuxostat XR 80 mg Capsule F2<br>* Febuxostat XR capsules formulation 2<br>Drug: Febuxostat XR 80 mg Capsule F3<br>* Febuxostat XR capsules formulation 3<br>Drug: Febuxostat XR 80 mg Capsule F4<br>* Febuxostat XR capsules formulation 4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Cmax: Maximum Observed Plasma Concentration for Febuxostat | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | 
| Mean AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Febuxostat | AUCt is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration. | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | 
| Mean AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | AUC∞ is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy