A Phase 1, Open-label, Randomized, Two-period, Two-treatment, Crossover Study to Evaluate the Effects of Food on the Pharmacokinetics of Urate After a Single Dose of Inosine in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- AUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity
研究概览
简要总结
The purpose of this study is to assess the effects of food on the amount of urate in the body after a single oral dose of inosine.
详细描述
Eighteen (18) eligible healthy male subjects will be randomly assigned to two groups with 9 subjects per group to receive a single oral dose of 1000 mg inosine with or without food on day 1 after an overnight fast. Subjects who receive inosine with food on day 1 will receive a second dose of inosine without food on day 8 after an overnight fast. Subjects who receive inosine without food on day 1 after an overnight fast will receive a second dose of inosine with food on day 8 after an overnight fast.
Subjects will be admitted to the clinic before dinner on days 0 and 7, the days before dosing, and will stay in the clinic for 48-h post-dose. During the clinic stay, blood samples will be taken for urate measurements.
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 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects between the ages of 18 and 65 years
- •Body-mass index between 18.0 kg/m2 and 32.0 kg/m2
- •If not surgically sterile, willing to refrain from donating sperm and willing to use appropriate birth control when engaging in sexual intercourse for a period of 90 days following the last dose of the study medication
- •Serum urate < 6.1 mg/dL (approximately 360 μM) at screening
- •Non-smokers for at least 6 months prior to screening
- •Adequate venous access at multiple sites in both arms
排除标准
- •History of alcohol or drug dependence in the past 2 years
- •Had 400 mL of whole blood collection within four months or 200 mL of whole blood collection or who had blood component collection within one month of the screening test
- •Used prescription or over-the-counter (OTC) drugs within 14 days prior to screening
- •Used vitamin preparations or supplements (including St. John's Wort and ginseng) within 28 days prior to the screening test
- •Not willing to refrain from alcohol, grapefruit, grapefruit juice or related products, caffeine consumption (including chocolate), and strenuous exercise within 72 h prior to day 1 and through the end of the PK study
- •Treated with an investigational drug within 30 days or 7 half-lives of the investigational drug, whichever is longer, prior to the first dose of study drug
- •Previously received inosine supplement within three months from the screening or subjects who have had any inosine and suffered an adverse reaction due to it
- •Known HIV disease
- •Had a febrile illness within 5 days prior to the first dose of study medication
- •Vaccinated within 30 days prior to the first dose of medication
- •Has gout or a history or suspicion of kidney stones
- •Determined by the investigator or sub-investigator to be unsuitable for participating in the study based on medical conditions
研究组 & 干预措施
Group 1, Inosine with Food
Group 1 subjects will take inosine with food on day 1 after an overnight fast and will take a second dose of inosine without food on day 8 after an overnight fast.
干预措施: Inosine (Drug)
Group 2, Inosine without Food
Group 2 subjects will take inosine without food on day 1 after an overnight fast and will take a second dose of inosine with food on day 8 after an overnight fast.
干预措施: Inosine (Drug)
结局指标
主要结局
AUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity
时间窗: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Tmax: Time of Maximum Serum Concentration
时间窗: -12 to 0 hr pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
T1/2: Apparent Terminal Half-life
时间窗: -12 to 0 pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Baseline Corrected Cmax: Baseline Corrected Maximum Serum Concentration
时间窗: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2). Negative concentrations were set to zero.
Baseline Corrected AUC (0-t): Baseline Corrected Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Serum Concentration)
时间窗: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2). Negative concentrations were set to zero.
Baseline Corrected AUC (0-inf): Baseline Corrected Area Under the Serum Concentration-time Curve From Time 0 to Infinity
时间窗: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose
Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2).
Baseline Corrected Tmax: Baseline Corrected Time of Maximum Serum Concentration
时间窗: -12 to 0 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose
Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2).
Cmax: Maximum Observed Serum Urate Concentration
时间窗: -12 to 0 hrs pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post-dose
AUC (0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Plasma Concentration)
时间窗: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Baseline Corrected T1/2: Baseline Corrected Apparent Terminal Half-life
时间窗: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2).
次要结局
- Safety Assessment (Vital Signs)(Up to 10 days after first study drug administration at Day 1 of Period 1)
- Safety Assessment: Adverse Events(Up to 10 days after first study drug administration at Day 1 of Period 1)
研究者
Michael Alan Schwarzschild
Director, Molecular Neurobiology Laboratory
Massachusetts General Hospital