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

NCT ID: NCT02841709

Last Updated: 2020-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-28
• Study Completion Date: 2017-06-29

Brief Summary

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.

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.

Conditions

Insomnia Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

ACT-541468

Intervention Type: DRUG

Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg

Placebo

Intervention Type: DRUG

Capsules for oral administration matching the ACT-541468 capsules

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.

Group Type: EXPERIMENTAL

ACT-541468

Intervention Type: DRUG

Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg

Placebo

Intervention Type: DRUG

Capsules for oral administration matching the ACT-541468 capsules

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.

Group Type: EXPERIMENTAL

ACT-541468

Intervention Type: DRUG

Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg

Placebo

Intervention Type: DRUG

Capsules for oral administration matching the ACT-541468 capsules

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.

Group Type: EXPERIMENTAL

ACT-541468

Intervention Type: DRUG

Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg

Placebo

Intervention Type: DRUG

Capsules for oral administration matching the ACT-541468 capsules

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.

Group Type: EXPERIMENTAL

ACT-541468

Intervention Type: DRUG

Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg

Placebo

Intervention Type: DRUG

Capsules for oral administration matching the ACT-541468 capsules

Interventions

ACT-541468

Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg

Intervention Type: DRUG

Placebo

Capsules for oral administration matching the ACT-541468 capsules

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Idorsia Pharmaceuticals Ltd.

Locations

Investigator Site

Brandon, Florida, United States

Investigator Site

Chicago, Illinois, United States

Investigator Site

Las Vegas, Nevada, United States

Investigator Site

New York, New York, United States

Investigator Site

Cincinnati, Ohio, United States

Investigator Site

Berlin, , Germany

Investigator Site

Berlin, , Germany

Investigator Site

Hamburg, , Germany

Investigator Site

Hanover, , Germany

Investigator Site

Schwerin, , Germany

Countries

United States; Germany

References

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.

Reference Type: DERIVED

PMID: 32341187 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AC-078A202

Identifier Type: -

Identifier Source: org_study_id