A Study of ACT-541468 in Healthy Japanese and Caucasian Subjects

Study Overview
=================
Brief Summary
-----------------
So far, ACT-541468 has been studied mainly in Caucasian subjects. The present study will bridge results obtained in Caucasian subjects to those in Japanese subjects.

Official Title
-----------------
A Single-center, Double-blind, Placebo-controlled, Randomized Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of Single- and Multiple-dose ACT-541468 in Healthy Japanese and Caucasian Subjects

Conditions
-----------------
Healthy Subjects

Intervention / Treatment
-----------------
* Drug: ACT-541468
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Signed informed consent form; Healthy male and female subjects aged between 20 and 50 years (inclusive) at screening; Negative serum pregnancy tests at screening and negative urine pregnancy test at Day 1 for women of childbearing potential and agreement to use a reliable method of contraception for at least 90 days after last study drug intake; Body mass index (BMI) of 18.0 to 26.0 kg/m2 (inclusive) at screening; Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests; Caucasian or Japanese ethnicity. Japanese subjects only: must be of native Japanese descent (all parents/grandparents of Japanese descent); must not have been away from Japan for more than 10 years (at screening visit); lifestyle should not have changed significantly since relocation from Japan. Key Exclusion Criteria: Any contraindication to the study treatments; History or clinical evidence of any disease or medical / surgical 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 treatments; History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0; Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT-541468 (25 mg)<br>8 Japanese and 8 Caucasian subjects will receive 25 mg (1 capsule) of ACT-541468 once daily for 5 days | Drug: ACT-541468<br>* Capsule<br>|
| Experimental: ACT-541468 (50 mg)<br>8 Japanese and 8 Caucasian subjects will receive 50 mg (2 capsules) of ACT-541468 once daily for 5 days | Drug: ACT-541468<br>* Capsule<br>|
| Placebo Comparator: Placebo<br>2 Japanese / 2 Caucasian subjects will receive 1 placebo capsule to match subjects in the ACT-541468 (25 mg) group and 2 other Japanese / 2 Caucasian subjects will receive 2 placebo capsules to match subjects in the ACT-541468 (50 mg) group | Drug: placebo<br>* Matching placebo capsule<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of ACT-541468 | The geometric mean Cmax values will be calculated based on pharmacokinetic (PK) blood sampling | From Day1 pre-dose to 48 hours after the last dose on Day 5 | 
| Area under the plasma concentration-time curves during a dosing interval [AUC(0-24)] of ACT-541468 | The geometric mean AUC(0-24) values will be calculated based on PK blood sampling | From Day1 pre-dose to 48 hours after the last dose on Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach Cmax (tmax) of ACT-541468 | The median tmax values will be calculated based on PK blood sampling | From Day1 pre-dose to 48 hours after the last dose on Day 5 | 
| Terminal half-life [t(1/2)] of ACT-541468 | The geometric mean t(1/2) values will be calculated based on PK blood sampling | From Day1 pre-dose to 48 hours after the last dose on Day 5 | 
| Area under the plasma concentration-time curves from time 0 to 8 h [AUC(0-8)] | The geometric mean AUC(0-8) values will be calculated based on PK blood sampling | From Day1 pre-dose to 48 hours after the last dose on Day 5 | 
| Incidence of treatment-emergent adverse events | The percentage of subjects with treatment-emergent adverse events will be reported | Up to Day 7 (end of study) | 
| Incidence of adverse events leading to premature discontinuation of study treatment | The number of subjects who prematurely discontinued the study treatment due to an adverse event will be reported | Up to Day 5 | 
| Incidence of any clinical relevant findings in ECG variables | The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported | Up to Day 7 (end of study) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
safety, Japanese, pharmacokinetics