A Clinical Study to Assess Next-day Driving Performance Following Administration of ACT-541468 in Middle-aged and Elderly Subjects

A Single-center, Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled, 4-way Cross-over Study to Assess Next-day Driving Performance Following Single and Multiple Evening Administrations of ACT-541468 in Middle-aged and Elderly Subjects

A clinical study to assess next-day driving performance following evening administrations of ACT-541468 in middle-aged and elderly subjects

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ACT-541468; Other: Placebo; Drug: Zopiclone 7.5 mg

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333
    • Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria

General criteria:

• Signed informed consent prior to any study-mandated procedure.
• Male and female subjects aged between 50 and 80 years (inclusive) at Screening.
• Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 pre-dose of each treatment period. They must consistently and correctly use a highly effective method of contraception, be sexually inactive, or have a vasectomized partner.
• Women of non-childbearing potential (i.e., postmenopausal, XY genotype, Turner syndrome, uterine agenesis).

Study-specific criteria

• Subject has a valid driving license for more than 5 years, has driven at least 3000 km/year on average in the past 2 years.
• Normal visual acuity (corrected or uncorrected).

Exclusion Criteria:

General criteria:

• Pregnant or lactating women.
• Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results.
• History or presence of rhythm disorders
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Study-specific criteria:

• Current or previous diagnosis of insomnia-related disorder according to the Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5) criteria.
• History of alcoholism, drug abuse, or regular use of sedative drugs or hypnotics within 3 years prior to Screening.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of more than 21 units or an average daily intake of more than 3 units (males), or defined as an average weekly intake of more than 14 units or an average daily intake of more than 2 units (females). One unit is equivalent to a half-pint (approx. 250 mL) of beer or 1 measure (25 mL) of spirits or 1 glass (125 mL) of wine.
• Modified Swiss Narcolepsy Scale total score < 0 at Screening or history of narcolepsy or cataplexy.
• Activities that disturb the circadian rhythm (e.g., working night shift, travelling across 3 time zones) within 2 weeks before (each) study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A (50 mg ACT-541468); 1 tablet of ACT-541468 50 mg + 1 tablet of ACT-541468 matching placebo + zopiclone matching placebo administered in the evening on Days 1-4 of Treatment Period A.	Drug: ACT-541468; Film-coated tablet for oral use at a dose strength of 50 mg.; Other: Placebo; Matching to maintain blinding.
Experimental: Treatment B (100 mg ACT-541468); 2 tablets of ACT-541468 50 mg + zopiclone matching placebo administered in the evening on Days 1-4 of Treatment Period B.	Drug: ACT-541468; Film-coated tablet for oral use at a dose strength of 50 mg.; Other: Placebo; Matching to maintain blinding.
Experimental: Treatment C (7.5 mg zopiclone); 2 tablets of ACT-541468 matching placebo + 1 capsule of zopiclone 7.5 mg administered in the evening on Days 1 and 4 of Treatment Period C. In the evenings of Days 2 and 3, subjects will receive placebo (i.e., 2 tablets of ACT-541468 matching placebo + zopiclone matching placebo).	Other: Placebo; Matching to maintain blinding.; Drug: Zopiclone 7.5 mg; Over-encapsulated to maintain blinding.
Experimental: Treatment D (placebo); 2 tablets of ACT-541468 matching placebo + zopiclone matching placebo administered in the evening on Days 1-4 of Treatment Period D.	Other: Placebo; Matching to maintain blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic endpoint: Driving performance as measured by the SDLB (difference from placebo, cm) using the Green Dino driving simulator - Day 2	SDLP = standard deviation of the lateral position	On Day 2 at 9 hours post dose. Duration of the test: 1 hour
Pharmacodynamic endpoint: Driving performance as measured by the SDLB (difference from placebo, cm) using the Green Dino driving simulator - Day 5	SDLP = standard deviation of the lateral position	On Day 5 at 9 hours post dose. Duration of the test: 1 hour

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.
• Investigators: Study Director: Clinical Pharmacologist, Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Actual): October 10, 2019
• Study Completion (Actual): October 10, 2019

Study Registration Dates

• First Submitted: March 21, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Actual): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Zopiclone
• Other Study ID Numbers: ID-078-108

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