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
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Idorsia Pharmaceuticals Ltd.
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- Change in Wake After Sleep Onset (WASO) From Baseline to Days 1 and 2
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: ACT-541468 (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: ACT-541468 (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: ACT-541468 (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: ACT-541468 (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: ACT-541468 (Drug)
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in Wake After Sleep Onset (WASO) From Baseline to Days 1 and 2
Time Frame: 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 Outcomes
- 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)