An Open Label, Randomized, Single Dose and Multiple Dose Trial to Assess the Pharmacokinetics of Obeticholic Acid (OCA)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Area under the concentration vs. time curve (AUCt)
研究概览
简要总结
This is a single center, open label, randomized, parallel design, single and multiple dose trial to evaluate the pharmacokinetics(PK), safety and tolerability of obeticholic acid (OCA).
详细描述
Twenty-four eligible subjects will be enrolled and randomized to 1 of 3 treatment groups (5 mg, 10 mg, or 25 mg) in a treatment ratio of 1:1:1 and no less than a ratio of 1:1 for female: male subjects. The study comprises single dose and multiple dose phases. The randomized dose administered in the single dose phase will be the subject's dose level for the multiple dose phase. A single dose of OCA (5 mg, 10 mg, or 25 mg) will be administered on Day 1. PK, safety, and tolerability will then be assessed for 3 days. On Day 4, the multiple dose phase will begin at the same dose level (5 mg, 10 mg, or 25 mg), with subjects receiving OCA once daily for 14 days. PK, safety, and tolerability will be assessed for 2 weeks at the clinical site following the last investigational product (IP) dose on Day 17. Subjects will be confined at the inpatient trial site from Day 0 until the morning of Day 30. They will return to the study site on Day 37 for follow up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- 未提供
排除标准
- •Subjects meeting any of the following criteria will be excluded from the trial:
- •Prior exposure to OCA (INT-747; 6-ECDCA)
- •History of known or suspected clinically significant hypersensitivity to OCA or any of its components
- •History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the large intestine, eg, inflammatory bowel disease (IBD)
- •History of gastrointestinal surgeries or gall bladder removal (cholecystectomy)
- •History or presence of a clinically significant cardiovascular, hepatic, diabetic, gastrointestinal, metabolic, neurologic, pulmonary, endocrine, psychiatric, or neoplastic disorder(s)
- •History of known or suspected clinically significant hypersensitivity to any drug, aside from penicillin
- •Ingestion of a prescription medication, including oral contraceptives and bile acid sequestrants, within 14 days prior to IP dosing or ingestion of an over the counter medication within 7 days prior to IP dosing
- •Participation in radiologic examinations involving parenteral administration of iodinated contrast materials within 2 weeks prior to screening, or subsequently through the end of trial participation
- •History or presence of alcohol abuse (defined as consumption of more than 210 mL of alcohol per week, or the equivalent of fourteen 4 ounces [oz] glasses of wine or fourteen 12 oz. cans/bottles of beer or wine coolers per week) or positive alcohol tests
- •History or presence of substance abuse within the past 2 years or positive drug screen tests
- •Smoker or use of any tobacco or nicotine containing products
- •Any screening laboratory test for which the results are not within the normal reference range and considered clinically significant
- •Participation in another investigational drug trial within 30 days prior to Day 0
- •History of noncompliance to medical regimens, or subjects who are considered to be potentially unreliable
- •Blood or plasma donation within 30 days prior to Day 0
- •Mental instability or incompetence
- •Presence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) at screening
- •Known or suspected Pregnancy
研究组 & 干预措施
OCA 5 mg
OCA 5 mg, 1 mg by mouth followed by 2 days of no investigational product (IP); then OCA 5 mg by mouth for 14 days.
干预措施: OCA 5 mg (Drug)
OCA 10 mg
OCA 10 mg, 1 mg by mouth followed by 2 days of no investigational product (IP); then OCA 10 mg by mouth for 14 days.
干预措施: OCA 10 mg (Drug)
OCA 25 mg
OCA 25 mg, 1 mg by mouth followed by 2 days of no investigational product (IP); then OCA 25 mg by mouth for 14 days.
干预措施: OCA 25 mg (Drug)
结局指标
主要结局
Area under the concentration vs. time curve (AUCt)
时间窗: 3 days - single dose, 33 days - Multi dose
Area under the concentration vs. time curve (AUCt) from time 0 to the last sampling time with measurable analyte concentration, calculated by the linear trapezoidal method
Area under the concentration vs. time curve from time 0 to 24 hours (AUC0-24)
时间窗: 24 hours
Area under the concentration vs. time curve from time 0 to 24 hours (AUC0-24) with measurable analyte concentration, calculated by the linear trapezoidal method
The ratio of each conjugate to OCA
时间窗: 3 days - single dose, 33 days - Multi dose
The ratio of each conjugate to OCA for exposure PK parameters for both single and multiple dose assessments.
Accumulation ratios (Rac) based on AUC, Cmax and Cmin
时间窗: 17 days
Accumulation ratios (Rac) based on AUC, Cmax and Cmin will be calculated for OCA and its conjugates (glyco-OCA and tauro-OCA) from Day 1 to Day 17
Maximum concentration (Cmax observed)
时间窗: 3 days - single dose, 33 days - Multi dose
Maximum concentration (observed) following single and multiple doses of OCA 5 mg, 10 mg, and 25 mg
Time to maximum concentration (tmax)
时间窗: 3 days - single dose, 33 days - Multi dose
Time to maximum concentration (tmax)
次要结局
未报告次要终点