Healthy Subjects
Conditions
Keywords
insomnia, Pharmacokinetics, Safety, Pharmacodynamics, Healthy
Brief summary
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.
Detailed description
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.
Interventions
DRUGACT-541468 (hydrochloride salt)
Hard-gelatin capsules (strength: 5 mg and 25 mg)
DRUGACT-541468 (free base)
Soft capsules (strength: 25 mg)
DRUGPlacebo
Placebo capsules matching the ACT-541468 formulations
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
Principal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events (AEs) | 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) | 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 | up to 72 hours post dosing | Laboratory tests including hematology, blood chemistry and urinalysis at scheduled time points during PArts A, B and C |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | AUC from time 0 to 8 hours after study drug administration \[AUC(0--8)\] and from time 0 to 24 hours after study drug administration \[AUC(0--24)\] will be determined after single (parts A and B) and multiple morning doses (Part A) as well as after multiple evening doses (Part C) |
| 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) | AUC from time 0 to infinity \[AUC(0--inf\], AUC from time 0 to time of the last measured concentration above the limit of quantification \[AUC(0--t)\] will be determined after single (Part B) and multiple morning doses (Part A) as well as after multiple evening doses (Part C) |
| 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 | saccadic eye movements (SEM) will be recorded by electrooculography and the average values of saccadic peak velocity of the SEM will be used as parameter of sedation |
| 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) | Cmax will be determined after single (Parts A and B) and multiple morning doses (Part A) as well as after repeated evening doses to identify the nighttime PK profile (Part C) |
| Change from baseline in body sway | Part A: Day 1 and Day 5; Part B: Day 1; Part C: Day 2 and Day 14 | Body sway will be assessed using a body sway meter |
| 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 | Subjects will rate sleepiness, alertness and mood using questionnaires |
| Visual motor coordination | Part A: Day 1 and Day 5; Part B: Day 1; Part C: Day 2 and Day 14 | Visual motor coordination will be assessed with the adaptive tracking test and the average tracking performance will be used as parameter of coordination |
| 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) | tmax will be determined after single (Parts A and B) and multiple morning doses (Part A) as well as after repeated evening doses to identify the nighttime PK profile (Part C) |
| 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) | t(1/2) will be determined after single (Parts A and B) and multiple morning doses (Part A) as well as after repeated evening doses (Part C) |
Countries
Netherlands
Outcome results
None listed