Assessment of Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Oral Doses of GLPG3067, the Combination of GLPG3067 and GLPG2222, and the Combination of GLPG3067, GLPG2222 and GLPG2737 in Healthy Female Subjects, Including a Relative Bioavailability and Food Effect Part for Single Dose of GLPG3067.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Galapagos NV
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Change versus placebo in the proportion of subjects with adverse events
研究概览
简要总结
The study is a First-in-Human, Phase I, randomized, double-blind, placebo-controlled, single center study, evaluating single and multiple ascending oral doses of GLPG3067 and the combination of GLPG3067 and GLPG2222 and the combination of GLPG3067,GLPG2222 and GLPG2737 given for 14 days in healthy women of non-childbearing potential.
The purpose of the study is to evaluate the safety and tolerability of single ascending oral doses and multiple ascending oral doses of GLPG3067 given to healthy women of non-childbearing potential compared to placebo, as well as of multiple oral doses of the combination of GLPG3067/GLPG2222 compared to matching placebo for each compound and multiple oral doses of the combination of GLPG3067/GLPG2222/GLPG2737 compared to matching placebo for each compound.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Female subject between 18-70 years of age, inclusive, on the date of signing the informed consent form (ICF).
- •Be of non-childbearing potential defined as surgically sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy), or post-menopausal (at least 12 consecutive months without menstruation, without an alternative medical cause [including hormone replacement therapy]).
- •Have a body mass index between 18-30 kg/m2, inclusive.
- •Judged by the investigator to be in good health based upon the results of a medical history, physical examination, vital signs, 12-lead triplicate electrocardiogram (ECG), and clinical safety laboratory tests prior to the initial study drug administration.
- •Discontinuation of all medications (including over-the-counter and/or prescription medication, dietary supplements, nutraceuticals, vitamins and/or herbal supplements, and hormonal replacement therapy for postmenopausal subjects) except occasional paracetamol (maximum dose of 2 g/day and maximum of 10 g/2 weeks) at least 2 weeks prior to the first study drug administration.
排除标准
- •Known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalization.
- •Clinically significant symptoms or illness in the 3 months before screening.
- •Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- •Any laboratory result considered by the investigator as clinically significant prior to study drug administration.
- •Creatinine clearance ≤80 mL/min using the Cockcroft-Gault formula for subjects aged ≤50 years, or creatinine clearance ≤70 mL/min using the Cockcroft-Gault formula for subjects aged >50 years. A 24-hour urine collection to determine the actual value may be performed to confirm creatinine clearance if required.
- •Clinically significant abnormalities of vital signs at screening.
- •Clinically relevant abnormalities detected on ECG regarding either rhythm or conduction (e.g. QT interval corrected for heart rate using Fridericia's formula [QTcF] >470 ms) or a known long QT syndrome. A first degree heart block or sinus arrhythmia will not be considered as a significant abnormality.
- •Participation in a drug, drug and device delivery system or combination, or biologic investigational research study within 8 weeks or 5 times the half-life of the investigational drug, if the half-life is known (whichever is longer) prior to initial study drug administration. Subjects who have been dosed previously with GLPG3067 in a clinical trial are allowed to participate Part 4 of this study as long as they completed their last follow-up visit or a washout period of 5 times the half-life of GLPG3067 (whichever is longer) after the last study drug administration is respected.
研究组 & 干预措施
GLPG3067 oral tablet fed 2
Single dose 2 of GLPG3067 oral tablet after a standardized breakfast.
干预措施: GLPG3067 oral tablet (Drug)
GLPG3067 single dose
Single dose of GLPG3067 oral suspension at up to 6 dose levels in ascending order.
干预措施: GLPG3067 single dose (Drug)
Placebo single dose
Single dose of Placebo oral suspension.
干预措施: Placebo single dose (Drug)
GLPG3067 oral suspension fed 1
Single dose 1 of GLPG3067 oral suspension after a standardized breakfast.
干预措施: GLPG3067 oral suspension (Drug)
GLPG3067 oral tablet fed 1
Single dose 1 of GLPG3067 oral tablet after a standardized breakfast.
干预措施: GLPG3067 oral tablet (Drug)
GLPG3067 oral tablet fasted 1
Single dose 1 of GLPG3067 oral tablet after an overnight fast.
干预措施: GLPG3067 oral tablet (Drug)
GLPG3067 oral tablet fed 2 high-fat high-calorie
Single dose 2 of GLPG3067 oral tablet after a high-fat high-calorie breakfast
干预措施: GLPG3067 oral tablet (Drug)
GLPG3067 multiple dose
Multiple doses of GLPG3067 oral suspension at up to 5 dose levels in ascending order.
干预措施: GLPG3067 multiple dose (Drug)
Placebo multiple dose
Multiple doses of Placebo oral suspension.
干预措施: Placebo multiple dose (Drug)
GLPG3067/GLPG2222 multiple dose
Multiple doses of GLPG3067 oral suspension combined with GLPG2222 oral tablet up to 2 dose levels in ascending order.
干预措施: GLPG3067/GLPG2222 multiple dose (Drug)
GLPG3067/GLPG2222 Placebo multiple dose
Multiple doses of GLPG3067 matching placebo oral suspension combined with GLPG2222 matching placebo oral tablet.
干预措施: GLPG3067/GLPG2222 Placebo multiple dose (Drug)
GLPG3067/GLPG2222/GLPG2737 multiple dose
Multiple doses of GLPG3067 oral tablet combined with GLPG2222 oral tablet and GLPG2737 oral capsule at up to 2 dose levels in ascending order.
干预措施: GLPG3067/GLPG2222/GLPG2737 multiple dose (Drug)
GLPG3067/GLPG2222/GLPG2737 Placebo multiple dose
Multiple doses of GLPG3067 matching placebo oral tablet combined with GLPG2222 matching placebo oral tablet and GLPG2737 matching placebo oral capsule.
干预措施: GLPG3067/GLPG2222/GLPG2737 Placebo multiple dose (Drug)
结局指标
主要结局
Change versus placebo in the proportion of subjects with adverse events
时间窗: Between screening and 14 days after the last dose
To assess safety and tolerability of single ascending doses, multiple ascending doses of GLPG3067 alone, or in combination with GLPG2222, or in combination with GLPG2222 and GLPG2737 versus placebo in healthy subjects
次要结局
- Ratio of 4-beta-hydroxycholesterol/cholesterol in plasma after multiple oral doses in healthy subjects(Day 1 predose and Day 14)
- Maximum observed plasma concentration of GLPG3067 (Cmax) given alone in fed state(Between Day 1 predose and 10 days after the last dose)
- Maximum observed plasma concentration of GLPG3067 (Cmax) given alone in fasted state(Between Day 1 predose and 10 days after the last dose)
- Concentration in plasma observed at 24 hours post dose (C24h) of GLPG3067 given alone in fed state(Between Day 1 predose and 10 days after the last dose)
- Concentration in plasma observed at 24 hours post dose (C24h) of GLPG3067 given alone in fasted state(Between Day 1 predose and 10 days after the last dose)
- Area under the plasma concentration-time curve of GLPG3067 (AUC0-t) given alone in fasted state(Between Day 1 predose and 10 days after the last dose)
- Maximum observed plasma concentration of GLPG3067 (Cmax) given alone or in combination with GLPG2222 or in combination with GLPG2222 and GLPG2737(Between Day 1 predose and 10 days after the last dose)
- Area under the plasma concentration-time curve of GLPG3067 (AUC0-t) given alone or in combination with GLPG2222 or in combination with GLPG2222 and GLPG2737(Between Day 1 predose and 10 days after the last dose)
- Area under the plasma concentration-time curve of GLPG3067 (AUC0-t) given alone in fed state(Between Day 1 predose and 10 days after the last dose)