Double-blind, Placebo-controlled, Randomized Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-541468: Part A: Multiple-ascending Doses in Healthy Young Adults After Morning Administration Part B: Single-ascending Doses in Healthy Elderly Subjects After Morning Administration Part C: Repeated Doses in Both Healthy Young Adults and Elderly Subjects After Evening Administration
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Number of participants with Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics (PK, or amount of drug over time in the body) and pharmacodynamics (PD, or effects on the body) of ACT-541468 following multiple ascending doses in healthy adults and following single ascending doses in healthy elderly subjects when administered in the morning. The safety, PK and PD of ACT-541468 will also be assessed after repeated evening administration of a selected dose in both healthy adults and elderly.
详细描述
In the first-in-man study, single doses of ACT-541468 administered in healthy young adults were well tolerated up to the dose level of 200 mg (inclusive) and yielded results compatible with possible sleep facilitating effects of ACT-541468. So the present study aimed to further investigate the effects of ACT-541468 after multiple ascending doses in healthy young subjects as well as after single ascending doses in elderly subjects (morning administrations). The effects of repeated administrations of a selected dose administered in the evening in both healthy adults and elderly, will also be investigated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent.
- •Adults aged from 18 to 45 years (inclusive) for Part A; elderly aged from 65 to 80 years (inclusive) for Part B; both adults from 18 to 45 years and elderly from 65 to 80 years (inclusive) for Part C.
- •Regular sleep pattern of at least 6 hours nocturnal sleep.
- •Young females must have negative pregnancy tests at screening and at pre-dose on Day 1 and use a reliable method of contraception
- •Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
- •Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) between 100-145 mmHg, 50-90 mmHg and 45-90 bpm (all inclusive) for young adults, respectively; SBP, DBP and PR between 100-160 mmHg, 50-95 mmHg and 45-100 bpm (all inclusive) for elderly, respectively.
- •Healthy on the basis of physical examination,electrocardiogram and laboratory tests.
排除标准
- •Principal exclusion criteria common to young adults and elderly:
- •Pregnant or lactating women.
- •Any contraindication to the study drugs.
- •History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs.
- •History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0 at screening.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.
- •Exclusion criteria for young adults only:
- •Treatment with any prescribed medications or over-the-counter medications within 2 weeks prior to study drug administration.
- •Exclusion criteria for elderly only:
- •Previous chronic treatment with any medication that is not given in stable doses and/or stable regimen within 2 months prior to screening.
- •Previous treatment with CNS-active drugs or within 2 months prior to screening.
- •Treatment with inhibitors of CYP3A4 (e.g., azole derivatives, ritonavir, clarithromycin) from 2 weeks prior to screening visit and up to EOS.
研究组 & 干预措施
Part A: ACT-541468 multiple ascending doses
Six young adults will receive ACT-541468 in the morning from Day 1 to Day 5 at each dose level in a sequential manner (total number of subjects = 18). Planned dose levels are 10, 25 and 75 mg per day
干预措施: ACT-541468 (hydrochloride salt) (Drug)
Part A: Placebo
For each ACT-541468 dose level tested in Part A, 2 young adults will receive matching placebo in the same conditions (total number of subjects = 6)
干预措施: Placebo (Drug)
Part B: ACT-541468 single ascending doses
Six elderly will receive ACT-541468 in the morning of Day 1 at each dose level in a sequential manner (total number of subjects = 18). Planned dose levels are 5, 15 and 25 mg
干预措施: ACT-541468 (hydrochloride salt) (Drug)
Part B: Placebo
For each ACT-541468 dose level tested in Part B, 2 elderly will receive matching placebo in the same conditions (total number of subjects = 6)
干预措施: Placebo (Drug)
Part C: repeated dose of ACT-541468
Sixteen young adults and eight elderly will receive ACT-541468 (planned dose: 25 mg) in the evening for 7 days (8 days for 6 of the 16 young adults).
干预措施: ACT-541468 (free base) (Drug)
Part C: Placebo
Four young adults and 2 elderly will receive matching placebo in the same conditions as subjects receiving the active compound in Part C
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with Adverse Events (AEs)
时间窗: up to 72 hours post dosing
Treatment emergent adverse events and treatment emergent serious adverse events will be evaluated throughout the study
Changes from baseline in ECG variables and vital signs (heart rate and blood pressure)
时间窗: up to 72 hours post dosing
12-lead electrocardiogram variables including RR, PR, QRS, QT and QTc intervals at scheduled time points during Parts A, B and C
Changes from baseline in clinical laboratory parameters
时间窗: up to 72 hours post dosing
Laboratory tests including hematology, blood chemistry and urinalysis at scheduled time points during PArts A, B and C
次要结局
- Maximum plasma concentration (Cmax) of ACT-541468 after daytime and bedtime intake(Part A: Day 1 and Day 5; Part B: Day 1; Part C: evening of Day 8 (pre-dose) and Day 9 (nighttime samples))
- Time to reach Cmax (tmax) of ACT-541468 after daytime and bedtime intake(Part A: Day 1 and Day 5; Part B: Day 1; Part C: evening of Day 8 (pre-dose) and Day 9 (nighttime samples))
- Areas under the plasma concentration-time curves [AUC(0-t), AUC(0-inf)] of ACT-541468 after daytime and bedtime intake(Part A: Day 5, from pre-dose up to 72 h post-dose; Part B: Day 1, at pre-dose up to 72 h post-dose; Part C: from the morning of Day 8 up to 60 h post-dose and from the evening of Day 8 (pre-dose) until 36 h post-dose (with nighttime samples))
- Terminal half-life [t(1/2)] after daytime and bedtime intake(Part A: Days 1 and 5, from pre-dose up to 72 h post-dose; Part B: Day 1, at pre-dose up to 72 h post-dose; Part C: from the morning of Day 8 up to 60 h post-dose and from the evening of Day 8 (pre-dose) until 36 h post-dose (with nighttime samples))
- Areas under the plasma concentration-time curves [AUC(0-8), AUC(0-24)] of ACT-541468 after daytime and bedtime intake(Part A: Days 1 and 5, from pre-dose up to 72 h post-dose; Part B: Day 1, at pre-dose up to 72 h post-dose; Part C: from the morning of Day 8 up to 60 h post-dose and from the evening of Day 8 (pre-dose) until 36 h post-dose (with nighttime samples))
- Sedation as measured by saccadic peak velocity(Part A: Day 1 and Day 5; Part B: Day 1; Part C: Day 2 and Day 14)
- Visual motor coordination(Part A: Day 1 and Day 5; Part B: Day 1; Part C: Day 2 and Day 14)
- Change from baseline in body sway(Part A: Day 1 and Day 5; Part B: Day 1; Part C: Day 2 and Day 14)
- Change from baseline in subjective cognitive effects(Part A: every day from Day 1 to Day 6; Part B: Day 1; Part C: Day 1 to Day 8)