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CompletedNCT02841709Updated Apr 24, 2020Results posted

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

A Phase 2 interventional study of ACT-541468 and Placebo in Insomnia Disorder, sponsored by Idorsia Pharmaceuticals Ltd.. Completed at 10 sites in 2 countries. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2020-04-24.

Sponsored by Idorsia Pharmaceuticals Ltd. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
58
Allocation
Randomized
Ages
65 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Insomnia Disorder

Keywords

  • insomnia
  • elderly
  • Polysomnography
03

In context

Sleep Initiation and Maintenance Disorders

1,856 studies on the registry are indexed under Sleep Initiation and Maintenance Disorders; 594 are open to participants now.

This study's enrollment of 58 is below the median of 73 across 1,631 interventional studies indexed under Sleep Initiation and Maintenance Disorders.

Browse Sleep Initiation and Maintenance Disorders studies →

Lead sponsor

Idorsia Pharmaceuticals Ltd. is the lead sponsor of 102 studies on the registry; 5 are open to participants now.

Of its 27 completed or terminated interventional studies of FDA-regulated products, 9 (33%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
65 Years and older
Sexes eligible
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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
58 participants (actual)

Study arms

  • 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 · Drug: Placebo

  • 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 · Drug: Placebo

  • 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 · Drug: Placebo

  • 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 · Drug: Placebo

  • 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 · Drug: Placebo

Interventions

  • DrugACT-541468

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

  • DrugPlacebo

    Capsules for oral administration matching the ACT-541468 capsules

06

What researchers measure

Primary outcomes

  1. 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)

    Time frame: Baseline to Day 1 and Day 2 of each treatment period

Secondary outcomes

  1. 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

    Time frame: Baseline to Day 1 and Day 2 of each treatment period

07

Results

Posted Apr 24, 2020

Participant flow

Conducted at 10 centers in 2 countries (USA and Germany)

1st Intervention
Participant flow — 1st Intervention
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed1211121211
Not completed00000
Washout Period 1
Participant flow — Washout Period 1
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed1211121211
Not completed00000
2nd Intervention
Participant flow — 2nd Intervention
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed1211121211
Not completed00000
Washout Period 2
Participant flow — Washout Period 2
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed1211121211
Not completed00000
3rd Intervention
Participant flow — 3rd Intervention
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed1211121211
Not completed00000
Washout Period 3
Participant flow — Washout Period 3
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed1211121211
Not completed00000
4th Intervention
Participant flow — 4th Intervention
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed1211121211
Not completed00000
Washout Period 4
Participant flow — Washout Period 4
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed1211121211
Not completed00000
5th Intervention
Participant flow — 5th Intervention
MilestoneSequence 1 (D4, D2, D3, D1 and P)Sequence 2 (D2, P, D4, D3 and D1)Sequence 3 (D3, D1, D2, P and D4)Sequence 4 (P, D4, D1, D2 and D3)Sequence 5 (D1, D3, P, D4 and D2)
Started1211121211
Completed101112129
Not completed20002
Withdrew: Adverse event20002

Outcome measures

PrimaryChange 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)

Time frame:
Baseline to Day 1 and Day 2 of each treatment period
Reported as:
Least squares mean · minutes
Change in Wake After Sleep Onset (WASO) From Baseline to Days 1 and 2
minutesACT-541468 5 mgACT-541468 10 mgACT-541468 25 mgACT-541468 50 mgPlacebo
Change in Wake After Sleep Onset (WASO) From Baseline to Days 1 and 2-18.9 ± 4.44-32.0 ± 4.50-45.1 ± 4.47-61.4 ± 4.44-13.6 ± 4.50
Statistical analysis
  • ACT-541468 5 mg vs ACT-541468 10 mg vs ACT-541468 25 mg vs ACT-541468 50 mg vs Placebo · Multiple Comparison Procedure-Model · p = <0.001
  • ACT-541468 5 mg vs Placebo · Linear mixed effects model · p = 0.258 · Ls mean difference: -5.4 · 95% CI -14.7 to 4.0Parameter Dispersion Type: Standard Error of the LS Mean
  • ACT-541468 10 mg vs Placebo · Linear mixed effects model · p = <0.001 · Ls mean difference: -18.4 · 95% CI -27.8 to -9.0Parameter Dispersion Type: Standard Error of the LS Mean
  • ACT-541468 25 mg vs Placebo · Linear mixed effects model · p = <0.001 · Ls mean difference: -31.5 · 95% CI -40.9 to -22.2
  • ACT-541468 50 mg vs Placebo · Linear mixed effects model · p = <0.001 · Ls mean difference: -47.8 · 95% CI -57.2 to -38.5
SecondaryChange 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

Time frame:
Baseline to Day 1 and Day 2 of each treatment period
Reported as:
Mean · Minutes
Change in Mean Latency to Persistent Sleep (LPS) From Baseline to Days 1 and 2
MinutesACT-541468 5 mgACT-541468 10 mgACT-541468 25 mgACT-541468 50 mgPlacebo
Change in Mean Latency to Persistent Sleep (LPS) From Baseline to Days 1 and 2-37.92 ± 48.76-44.61 ± 41.28-44.81 ± 41.56-44.88 ± 44.22-33.88 ± 41.74

Adverse events

Collected over Start of screening until the end of the safety follow-up period.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Single-blind Placebo (Run-in Period)0/58 (0%)0/58 (0%)7/58 (12.1%)
Placebo0/54 (0%)0/54 (0%)11/54 (20.4%)
ACT-541468 5 mg0/56 (0%)0/56 (0%)14/56 (25%)
ACT-541468 10 mg0/54 (0%)0/54 (0%)12/54 (22.2%)
ACT-541468 25 mg0/55 (0%)0/55 (0%)10/55 (18.2%)
ACT-541468 50 mg0/56 (0%)0/56 (0%)16/56 (28.6%)
Most frequent other events
Showing 10 of 58
Most frequent other events
EventSingle-blind Placebo (Run-in Period)PlaceboACT-541468 5 mgACT-541468 10 mgACT-541468 25 mgACT-541468 50 mg
FatigueGeneral disorders0/582/540/561/540/554/56
Back painMusculoskeletal and connective tissue disorders0/582/540/560/541/550/56
Gait disturbanceGeneral disorders1/580/542/561/541/551/56
NasopharyngitisInfections and infestations0/581/541/561/540/552/56
DizzinessNervous system disorders0/580/542/561/540/550/56
HeadacheNervous system disorders2/581/542/560/541/551/56
Bundle branch block leftCardiac disorders0/581/540/560/540/550/56
Cerumen impactionEar and labyrinth disorders0/581/540/560/540/550/56
Abdominal discomfortGastrointestinal disorders0/581/540/560/540/550/56
Defaecation urgencyGastrointestinal disorders0/580/541/561/541/550/56

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)All Study Participants
<=18 years0
Between 18 and 65 years57
>=65 years1
Age, Continuous
Age, Continuous(years)All Study Participants
Median69 (65 to 85)
Sex: Female, Male
Sex: Female, Male(Participants)All Study Participants
Female39
Male19
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)All Study Participants
Hispanic or Latino1
Not Hispanic or Latino57
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Study Participants
American Indian or Alaska Native1
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American3
White54
More than one race0
Unknown or Not Reported0
Insomnia Severity Index
Insomnia Severity Index(units on a scale)All Study Participants
Mean20 (15 to 28)
08

Study locations

10 sites
  • Investigator Site
    Brandon, Florida 33511, United States
  • Investigator Site
    Chicago, Illinois 60634, United States
  • Investigator Site
    Las Vegas, Nevada 89104, United States
  • Investigator Site
    New York, New York 10019, United States
  • Investigator Site
    Cincinnati, Ohio 45255, United States
  • Investigator Site
    Berlin, 10115, Germany
  • Investigator Site
    Berlin, 10117, Germany
  • Investigator Site
    Hamburg, 20253, Germany
  • Investigator Site
    Hannover, 30159, Germany
  • Investigator Site
    Schwerin, 19053, Germany
09

References and documents

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. PubMed 32341187 ↗

Study documents

  • Study protocol · Aug 10, 2016
  • Statistical analysis plan · Jul 12, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 24, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02841709
Lead sponsor
Idorsia Pharmaceuticals Ltd.
Responsible party
Sponsor
First posted
Jul 22, 2016
Start date
Nov 28, 2016
Primary completion
May 31, 2017
Completion
Jun 29, 2017
Results posted
Apr 24, 2020
Last update
Apr 24, 2020

Study contacts

Clinical Trials
study director · Idorsia Pharmaceuticals Ltd.

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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