Insomnia DisorderPhase 2NCT02841709

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

A Phase 2 study testing ACT-541468 in people with Insomnia Disorder, run by Idorsia Pharmaceuticals Ltd. at 10 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 more about this study

Who is it for?: Ages 65 years and older
Conditions the study is for: Insomnia Disorder
What is being tested?: ACT-541468
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 58 participants
Where: 10 sitesin 2 countries
Study dates: 28 Nov 2016to 29 Jun 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 65 years and older
All sexes
No healthy volunteers
Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

10 sites in 2 countries.

Country

City, postcode or hospital

10 sites in 2 countries

United States5 sites

Investigator Site
Brandon, Florida, 33511
Investigator Site
Chicago, Illinois, 60634
Investigator Site
Cincinnati, Ohio, 45255
Investigator Site
Las Vegas, Nevada, 89104
Investigator Site
New York, New York, 10019

Other trials in United States

Germany5 sites

Investigator Site
Berlin, 10115
Investigator Site
Berlin, 10117
Investigator Site
Hamburg, 20253
Investigator Site
Hanover, 30159
Investigator Site
Schwerin, 19053

Other trials in Germany

About this study

Official title: 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.

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.

Conditions: Insomnia Disorder
Being tested: ACT-541468, Placebo
Keywords: insomnia, elderly, Polysomnography
Medical subject headings: Sleep Initiation and Maintenance Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ACT-541468Drug
Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg
PlaceboDrug
Capsules for oral administration matching the ACT-541468 capsules

Study groups in NCT02841709
Study group	Role	What they receive
Sequence 1	Experimental	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. Receives: Drug: ACT-541468; Drug: Placebo
Sequence 2	Experimental	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. Receives: Drug: ACT-541468; Drug: Placebo
Sequence 3	Experimental	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. Receives: Drug: ACT-541468; Drug: Placebo
Sequence 4	Experimental	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. Receives: Drug: ACT-541468; Drug: Placebo
Sequence 5	Experimental	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. Receives: Drug: ACT-541468; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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
Measured: Baseline to Day 1 and Day 2 of each treatment period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Nov 201629 Jun 2017

First posted22 Jul 2016 (estimated)
Study start28 Nov 2016
Primary completion31 May 2017
Study completion29 Jun 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Insomnia DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02841709
Sponsor's protocol ID: AC-078A202
Status last verified: Apr 2020
First submitted: 20 Jul 2016
Last updated: 24 Apr 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Insomnia Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02841709
Acronym / sponsor ID: AC-078A202
Conditions: Insomnia Disorder
Keywords: insomnia, elderly, Polysomnography
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
Study start: 28 Nov 2016 (actual)
Primary completion: 31 May 2017 (actual)
Study completion: 29 Jun 2017 (actual)
First posted: 22 Jul 2016 (estimated)
Results: Posted 24 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Sequence 1	Experimental	Drug: ACT-541468, Drug: PlaceboEach 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	Experimental	Drug: ACT-541468, Drug: PlaceboEach 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	Experimental	Drug: ACT-541468, Drug: PlaceboEach 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	Experimental	Drug: ACT-541468, Drug: PlaceboEach 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	Experimental	Drug: ACT-541468, Drug: PlaceboEach 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.

Who may qualify

Ages: 65 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ACT-541468Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg	Drug	Sequence 1, Sequence 2, Sequence 3, Sequence 4, Sequence 5
PlaceboCapsules for oral administration matching the ACT-541468 capsules	Drug	Sequence 1, Sequence 2, Sequence 3, Sequence 4, Sequence 5

Primary outcome

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)

1 secondary outcome

Change in Mean Latency to Persistent Sleep (LPS) From Baseline to Days 1 and 2
Time frame: Baseline to Day 1 and Day 2 of each treatment period

Results and safety

Results posted to the registry on 24 Apr 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequence 1 (D4, D2, D3, D1 and P)	12	12
Sequence 2 (D2, P, D4, D3 and D1)	11	11
Sequence 3 (D3, D1, D2, P and D4)	12	12
Sequence 4 (P, D4, D1, D2 and D3)	12	12
Sequence 5 (D1, D3, P, D4 and D2)	11	11

Primary outcome: 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. Least squares mean (Standard Error). Unit: minutes

Measure	ACT-541468 5 mg n = 56	ACT-541468 10 mg n = 54	ACT-541468 25 mg n = 55	ACT-541468 50 mg n = 56	Placebo n = 54
Value	-18.9 (4.44)	-32.0 (4.50)	-45.1 (4.47)	-61.4 (4.44)	-13.6 (4.50)

ACT-541468 5 mg vs ACT-541468 10 mg vs ACT-541468 25 mg vs ACT-541468 50 mg vs Placebo: p <0.001, Multiple Comparison Procedure-Model
ACT-541468 5 mg vs Placebo: LS mean difference: -5.4 (95% CI -14.7 to 4.0), p = 0.258, Linear mixed effects model
ACT-541468 10 mg vs Placebo: LS mean difference: -18.4 (95% CI -27.8 to -9.0), p <0.001, Linear mixed effects model

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Start of screening until the end of the safety follow-up period.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Single-blind Placebo (Run-in Period)	0 of 58 (0%)	7 of 58 (12.1%)	0 of 58
Placebo	0 of 54 (0%)	11 of 54 (20.4%)	0 of 54
ACT-541468 5 mg	0 of 56 (0%)	14 of 56 (25%)	0 of 56
ACT-541468 10 mg	0 of 54 (0%)	12 of 54 (22.2%)	0 of 54
ACT-541468 25 mg	0 of 55 (0%)	10 of 55 (18.2%)	0 of 55
ACT-541468 50 mg	0 of 56 (0%)	16 of 56 (28.6%)	0 of 56

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32341187Zammit 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Idorsia Pharmaceuticals Ltd.

10 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ACT-541468 in people with Insomnia Disorder, run by Idorsia Pharmaceuticals Ltd. at 10 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02841709, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2020.