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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: ACT-541468; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACT-541468 (25 mg); 8 Japanese and 8 Caucasian subjects will receive 25 mg (1 capsule) of ACT-541468 once daily for 5 days	Drug: ACT-541468; Capsule
Experimental: ACT-541468 (50 mg); 8 Japanese and 8 Caucasian subjects will receive 50 mg (2 capsules) of ACT-541468 once daily for 5 days	Drug: ACT-541468; Capsule
Placebo Comparator: Placebo; 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; Matching placebo capsule

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)

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Actual): April 24, 2017
• Study Completion (Actual): April 26, 2017

Study Registration Dates

• First Submitted: March 24, 2017
• First Submitted That Met QC Criteria: March 29, 2017
• First Posted (Actual): April 5, 2017

Study Record Updates

• Last Update Posted (Actual): July 10, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; Japanese
• Other Study ID Numbers: AC-078-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No