A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of HS-10518 in Healthy Adult Premenopausal Females in China
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 48
- 主要终点
- Incidence of Adverse Events (AE) as assessed by CTCAE v4.0
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HS-10518 in healthy adult premenopausal females in China.
详细描述
This is a double-blind, placebo-controlled, multiple-dose, single-center phase 1 study in Chinese healthy premenopausal females aged 18-45 years with a regular menstrual cycle (26-32 days). The main purpose of the study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HS-10518, a gonadotropin-releasing hormone antagonist.
About 48 eligible female subjects will be enrolled. The study contains four cohorts.
In each cohort, participants will be randomly assigned to the HS-10518 arm or the placebo arm in a 3:1 ratio. HS-10518/matching placebo will be administered from Day 1 to Day 7. The study duration of each participant is up to ~10 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •• Subject is a healthy premenopausal female aged 18-45 (inclusive) at Screening;
- •Subject has a body weight ≥45kg with a body mass index (BMI) of 18-28 kg/m^2 (inclusive);
- •Subject has a normal menstrual cycle for no less than 2 years (Cycle: 26-32 days, menstrual period: 2-7 days), and have a positive ovulation test in the cycle prior to drug administration;
- •Subject is willing to use highly effective, non-hormone contraceptive methods from signing the consent form until 3 months after the last dose;
- •Subject agrees to draw blood in pre-specified time points throughout the study and to attend the follow-up visit;
- •Subject is able to understand the purpose, process and potential adverse events of the study, and is willing to sign a written informed consent form.
排除标准
- •• Subject took caffeine-rich or xanthine-rich food or drink (e.g. coffee, tea, chocolate, cola, etc.), tobacco or alcoholic products within 48 hours prior to drug administration;
- •Subject took any grapefruit, grapefruit juice or other products within 7 days prior to first dose of study drug;
- •Subject has a positive breath alcohol test or a history of alcohol abuse;
- •Subject is a heavy smoker, or smokes ≥5 cigarettes per day, or is not able to cease smoking during the study (including e-cigarette);
- •Subject has a history of drug abuse or a positive urine drug test;
- •Subject is pregnant, breastfeeding or has a positive pregnancy test at Screening
研究组 & 干预措施
HS-10518 Dose 1
Dose level 1 of HS-10518, QD, orally, 7 days
干预措施: HS-10518 (Drug)
Placebo Dose 1
Dose level 1 of matching placebo, QD, orally, 7 days
干预措施: Placebo (Drug)
HS-10518 Dose 2
Dose level 2 of HS-10518, QD, orally, 7 days
干预措施: HS-10518 (Drug)
Placebo Dose 2
Dose level 2 of matching placebo, QD, orally, 7 days
干预措施: Placebo (Drug)
HS-10518 Dose 3
Dose level 3 of HS-10518, QD, orally, 7 days
干预措施: HS-10518 (Drug)
Placebo Dose 3
Dose level 3 of matching placebo,QD, orally, 7 days
干预措施: Placebo (Drug)
HS-10518 Dose 4
Dose level 4 of HS-10518, QD, orally, 7 days
干预措施: HS-10518 (Drug)
Placebo Dose 4
Dose level 4 of matching placebo, QD, orally, 7 days
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Adverse Events (AE) as assessed by CTCAE v4.0
时间窗: From screening to day 16
Assessment of safety and tolerability of multiple-dose HS-10518 in healthy female subjects in terms of the frequency, severity and causality of AEs, serious adverse events (SAEs) and AEs leading to study discontinuation. CTCAE v4.0 will be used for classification and severity determination.
Assessment of safety and tolerability of HS-10518 in terms of the frequency, severity and causality of AEs, serious adverse events (SAEs) and AEs leading to study discontinuation.
时间窗: From screening to day 16
Incidence of any markedly abnormal standard vital sign measurements is collected throughout study.
Incidence of clinically significant abnormal findings in 12-lead electrocardiogram (ECG)
时间窗: From screening to day 16
Incidence of any clinically significant abnormal findings in 12-lead ECG is collected throughout study.
次要结局
- Plasma pharmacokinetic (PK) parameter: Maximum plasma concentration (Cmax)(Day 1 (after the first dose) and Day 7-10 (after the last dose))
- PK parameter :Time of maximum observed plasma concentration (Tmax)(Day 1 (after the first dose) and Day 7-10 (after the last dose))
- PK parameter: Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t)(Day 1 (after the first dose) and Day 7-10 (after the last dose))