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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 主要终点
- Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Has an estimated glomerular filtration rate ≥90 mL/min.
- •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.
- •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.
- •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.
- •Able to attend all the visits scheduled in the study.
- •Willing to refrain from strenuous exercise from Day -1 until Study Exit (Day 3 of Period 3).
排除标准
- •Hypersensitivity to Febuxostat or to any of the components of the formulation.
- •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.
- •Has uncontrolled, clinically significant 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 xanthine oxidase (XO) inhibitor, xanthine compounds, Febuxostat or any component of the formulation of Febuxostat tablets, or to caffeine.
- •Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1 of Period 1).
- •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.
- •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.
- •Intends to impregnate others or donate sperm during the course of this study or for 30 days post last dose.
- •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.
- •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]).
- •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
- •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.
- •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).
- •Has poor peripheral venous access.
- •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
- •Has a Screening abnormal (clinically significant) electrocardiogram (ECG).
- •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.
研究组 & 干预措施
Treatment Sequence ABC
Febuxostat extended release (XR) 80 mg, capsules, orally, once on Day 1 of Period 1 after a high-fat meal, followed by a 7-day washout period, followed by febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 2 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80, capsules, orally, once on Day 1 of Period 3 after a 10-hour fast.
干预措施: Febuxostat XR (Drug)
Treatment Sequence BCA
Febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 1 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 2 after a 10-hour fast, followed by a 7-day washout period, followed by Febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 3 after a high-fat meal.
干预措施: Febuxostat XR (Drug)
Treatment Sequence CAB
Febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 1 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 2 after a high-fat meal, followed by a 7-day washout period, followed by febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 3 after a 10-hour fast.
干预措施: Febuxostat XR (Drug)
结局指标
主要结局
Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
时间窗: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Participant blood samples were collected pre-dose and following a single oral dose.
Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 40 mg (Regimen B) and Febuxostat XR 80 mg (Regimen C) in Fasted States
时间窗: Day 1 pre-dose and at multiple time points (up to 48 hours) post dose
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Participant blood samples were collected pre-dose and following a single oral dose.
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
时间窗: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
AUCinf is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. Participant blood samples were collected pre-dose and following a single oral dose.
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
时间窗: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
AUCt is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUCt) Participant blood samples were collected pre-dose and following a single oral dose.
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
时间窗: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
AUCinf is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. Participant blood samples were collected pre-dose and following a single oral dose.
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
时间窗: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
AUCt is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration. Participant blood samples were collected pre-dose and following a single oral dose.
次要结局
未报告次要终点