Efficacy and Safety of ACT-541468 in Elderly Subjects With Insomnia Disorder

Multi-center, Double-blind, Randomized, Placebo-controlled, 5-period, 5-treatment Crossover, Polysomnography Dose-response Study to Assess the Efficacy and Safety of ACT-541468 in Elderly Subjects With Insomnia Disorder

This study evaluates the dose response of ACT-541468 on the change of wake after sleep onset (WASO) assessed by polysomnography (PSG) on the first 2 days of each treatment period.

Study Overview

• Status: Completed
• Conditions: Insomnia Disorder
• Intervention / Treatment: Drug: ACT-541468; Drug: Placebo

Detailed Description

The study consists of 3 phases: a screening phase, a double-blind treatment phase consisting of 5 periods, and a safety follow-up phase. Safety is monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10115
    • Investigator site
  • Berlin, Germany, 10117
    • Investigator site
  • Hamburg, Germany, 20253
    • Investigator site
  • Hannover, Germany, 30159
    • Investigator site
  • Schwerin, Germany, 19053
    • Investigator site
• United States
  • Florida
    • Brandon, Florida, United States, 33511
      • Investigator site
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Investigator site
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Investigator site
  • New York
    • New York, New York, United States, 10019
      • Investigator site
  • Ohio
    • Cincinnati, Ohio, United States, 45255
      • Investigator site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent prior to any study-mandated procedure.
• Male or female aged ≥ 65 years.
• Body mass index (BMI): 18.5 ≤ BMI (kg/m2 ) < 32.0
• Insomnia disorder according to DSM-5 criteria.
• Self-reported history of insufficient sleep quantity.
• Insufficient sleep quantity as collected subjectively in the sleep diary and validated objectively by polysomnography.
• Insomnia Severity Index score ≥ 15.

Exclusion Criteria:

• Any current history of sleep disorder other than insomnia, or any lifetime history of related breathing disorder, periodic limb movement disorder, restless legs syndrome, circadian rhythm disorder, rapid eye movement (REM) behavior disorder, or narcolepsy.
• Self-reported usual daytime napping ≥ 1 hour per day, and ≥ 3 days per week.
• Caffeine consumption ≥ 600 mg per day.
• Shift work within 2 weeks prior to the screening visit, or planned shift work during study.
• Travel ≥ 3 time zones within 1 week prior to the screening visit, or planned travel ≥ 3 time zones during study.
• Hematology or biochemistry test results deviating from the normal range to a clinically relevant extent as per judgment of the Investigator.
• AST and/or ALT > 2 × ULN and/or bilirubin > 1.5 × ULN (except known history of Gilbert's syndrome);
• Severe renal impairment (known or defined as estimated creatinine clearance < 30 mL/min);
• History or clinical evidence of any disease or medical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the study assessments.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: D4, D2, D3, D1 and P, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout.	Drug: ACT-541468; Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg; Drug: Placebo; Capsules for oral administration matching the ACT-541468 capsules
Experimental: Sequence 2; Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: D2, P, D4, D3 and D1, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout.	Drug: ACT-541468; Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg; Drug: Placebo; Capsules for oral administration matching the ACT-541468 capsules
Experimental: Sequence 3; Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: D3, D1, D2, P and D4, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout.	Drug: ACT-541468; Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg; Drug: Placebo; Capsules for oral administration matching the ACT-541468 capsules
Experimental: Sequence 4; Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: P, D4, D1, D2, D3, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout.	Drug: ACT-541468; Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg; Drug: Placebo; Capsules for oral administration matching the ACT-541468 capsules
Experimental: Sequence 5; Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: D1, D3, P, D4 and D2 with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout.	Drug: ACT-541468; Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg; Drug: Placebo; Capsules for oral administration matching the ACT-541468 capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Wake After Sleep Onset (WASO) From Baseline to Days 1 and 2	WASO is the time in minutes spent awake after onset of persistent sleep until lights on as determined by polysomnography (PSG)	Baseline to Day 1 and Day 2 of each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Latency to Persistent Sleep (LPS) From Baseline to Days 1 and 2	LPS is the duration of time in minutes from lights off to persistent sleep onset as determined by PSG	Baseline to Day 1 and Day 2 of each treatment period

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• Zammit G, Dauvilliers Y, Pain S, Sebok Kinter D, Mansour Y, Kunz D. Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia disorder. Neurology. 2020 May 26;94(21):e2222-e2232. doi: 10.1212/WNL.0000000000009475. Epub 2020 Apr 27.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2016
• Primary Completion (Actual): May 31, 2017
• Study Completion (Actual): June 29, 2017

Study Registration Dates

• First Submitted: July 20, 2016
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (Estimate): July 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: elderly; insomnia; Polysomnography
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: AC-078A202

Plan for Individual participant data (IPD)

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