Clinical trial NCT02374164: Food Effect Study of Febuxostat XR in Healthy Participants
Official title: A Phase 1, Open-Label, Single-Center, Randomized, 3-Way Crossover Study to Assess the Effect of Food on the Bioavailability of a Single Oral Dose of 80 mg Febuxostat Extended-Release Formulation and the Pharmacokinetics of a Single Oral Dose of 40 mg and 80 mg Febuxostat Extended-Release Formulation in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gout
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-02-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of food on the bioavailability of febuxostat after a single oral dose of 80 mg febuxostat XR and to evaluate the pharmacokinetics (PK) of febuxostat after single oral doses of 40 and 80 mg febuxostat XR.

Detailed description: The drug being tested in this study is called febuxostat extended- release (XR). This study is evaluating the effect of food on how febuxostat-XR moves throughout the body. This study will also look at the side effects and all safety results in people who took the study drug.

This 3-way crossover study will enroll approximately 36 participants. Eligible participants will be randomly (by chance) assigned to one of the 3 treatment sequences at 1:1:1 ratio. Sequence defines the order in which participants receive Regimens A (febuxostat XR 80 mg after a high fat meal), B (febuxostat XR 40 mg after fasting) and C (febuxostat XR 80 mg after fasting):

Sequence 1: A, B, C

Sequence 2: B, C, A

Sequence 3: C, A, B The dose in a period and the dose in the subsequent period will be separated by a minimum 7-day washout interval. This single-centre trial will be conducted in the United States.

Participants will make multiple visits to the clinic including three 4-day periods of confinement to the clinic, and will be contacted by telephone 30 days after last dose of study drug for a follow-up assessment.

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Eligibility criteria: Inclusion Criteria:

1. Has an estimated glomerular filtration rate ≥90 mL/min.
2. Weighs at least 50 kg (110 pounds) and has a body mass index (BMI) from 18.0 to 30.0 kg/m\^2, inclusive, at Screening.
3. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from the signing of the informed consent throughout the duration of the study and for 30 days after the last dose.
4. 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 throughout the duration of the study and for 30 days after the last dose.
5. Able to attend all the visits scheduled in the study.
6. Willing to refrain from strenuous exercise from Day -1 until Study Exit (Day 3 of Period 3).

Exclusion Criteria:

1. Hypersensitivity to Febuxostat or to any of the components of the formulation.
2. Has received any investigational compound within 30 days prior to the first dose of study medication.
3. Has received febuxostat in a previous clinical study or as a therapeutic agent.
4. Has uncontrolled, clinically significant disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
5. Has a known hypersensitivity to any xanthine oxidase (XO) inhibitor, xanthine compounds, Febuxostat or any component of the formulation of Febuxostat tablets, or to caffeine.
6. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1 of Period 1).
7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
8. Is pregnant or lactating or intending to become pregnant before, during, or within 30 days post last dose; or intending to donate ova during such time period.
9. Intends to impregnate others or donate sperm during the course of this study or for 30 days post last dose.
10. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma, hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking febuxostat XR, or a similar drug in the same class, or a disease that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
11. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention \[eg, cholecystectomy\]).
12. Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1 of Period 1.
13. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or a known history of human immunodeficiency virus infection.
14. Has used nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 28 days prior to Check-in (Day -1 of Period 1) or is unwilling to agree to abstain from nicotine-containing products. Cotinine test is positive at Screening or Check-in (Day 1 of Period 1).
15. Has poor peripheral venous access.
16. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis) or had a transfusion of any blood product within 30 days prior to Day 1 of Period 1.
17. Has a Screening abnormal (clinically significant) electrocardiogram (ECG).
18. Has abnormal Screening or Day -1 of Period 1 laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 x the upper limit of normal.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
timeFrame: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
measure: Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 40 mg (Regimen B) and Febuxostat XR 80 mg (Regimen C) in Fasted States
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post dose
measure: AUCt: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
timeFrame: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
measure: AUCt: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for Febuxostat XR 40 mg (Regimen B) and Febuxostat XR 80 mg (Regimen C) in Fasted States
timeFrame: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
measure: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
timeFrame: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
measure: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Febuxostat XR 40 mg (Regimen B) and Febuxostate XR 80 mg (Regimen C) in Fasted States
timeFrame: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
Secondary outcomes:
Other outcomes:
Locations:
city: Austin
country: United States
state: Texas
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: