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

Phase 2

Completed

Conditions: Insomnia Disorder

Interventions: Drug: ACT-541468
Drug: Placebo

Registration Number: NCT02841709

Lead Sponsor: Idorsia Pharmaceuticals Ltd.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 58

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence 1	Placebo	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.
Sequence 2	Placebo	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.
Sequence 3	Placebo	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.
Sequence 4	Placebo	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.
Sequence 5	Placebo	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.
Sequence 1	ACT-541468	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.
Sequence 5	ACT-541468	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.
Sequence 2	ACT-541468	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.
Sequence 3	ACT-541468	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.
Sequence 4	ACT-541468	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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