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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACT-541468 | Drug | Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Baseline to Day 1 and Day 2 of each treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline to Day 1 and Day 2 of each treatment period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Idorsia Pharmaceuticals Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site | Brandon | Florida | 33511 | United States | ||
| Investigator Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32341187 | Derived | 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. |
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Screening phase: From informed consent to randomization, lasting a max. of 28 days and comprising a screening period (screening visit + at least 7 days at home) and a run-in period (2 consecutive PSG nights on SB placebo, + 5-12 days at home with no treatment). Note: More subjects were randomized (n = 58) than originally planned (n = 50).
Conducted at 10 centers in 2 countries (USA and Germany)
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 (D4, D2, D3, D1 and P) | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12-day washout. |
| FG001 | Sequence 2 (D2, P, D4, D3 and D1) | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12-day washout. |
| FG002 | Sequence 3 (D3, D1, D2, P and D4) | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12-day washout. |
| FG003 | Sequence 4 (P, D4, D1, D2 and D3) | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received one dose (D) of ACT-541468 or placebo orally in the following order: P, D4, D1, D2, and D3, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period was separated from the next one by a 5- to 12-day washout. |
| FG004 | Sequence 5 (D1, D3, P, D4 and D2) | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12-day washout. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1st Intervention |
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| Washout Period 1 |
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| 2nd Intervention |
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| Washout Period 2 |
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| 3rd Intervention |
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| Washout Period 3 |
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| 4th Intervention |
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| Washout Period 4 |
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| 5th Intervention |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | Posted | Least Squares Mean | Standard Error | minutes | Baseline to Day 1 and Day 2 of each treatment period |
|
Start of screening until the end of the safety follow-up period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Single-blind Placebo (Run-in Period) | Single-blind placebo was administered during the run-in period. Placebo: Capsules for oral administration matching the ACT-541468 capsules |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bundle branch block left | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials Disclosure Desk | Idorsia Pharmaceuticals Ltd | +41 588 441977 | clinical-trials-disclosure@idorsia.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 10, 2016 | Feb 26, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 12, 2017 | Feb 26, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D007319 | Sleep Initiation and Maintenance Disorders |
| ID | Term |
|---|---|
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000634383 | daridorexant |
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|
| 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. |
|
| Placebo | Drug | Capsules for oral administration matching the ACT-541468 capsules |
|
| 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 | Hanover | 30159 | Germany |
| Investigator Site | Schwerin | 19053 | Germany |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Insomnia Severity Index | Range 0 - 28. Total score categories: 0-7 = No clinically significant insomnia 8-14 = Subthreshold insomnia 15-21 = Clinical insomnia (moderate severity) 22-28 = Clinical insomnia (severe) | Mean | Full Range | units on a scale |
|
| OG001 |
| ACT-541468 10 mg |
Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules |
| OG002 | ACT-541468 25 mg | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules |
| OG003 | ACT-541468 50 mg | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules |
| OG004 | Placebo | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | Minutes | Baseline to Day 1 and Day 2 of each treatment period |
|
|
|
| 0 |
| 58 |
| 0 |
| 58 |
| 7 |
| 58 |
| EG001 | Placebo | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules | 0 | 54 | 0 | 54 | 11 | 54 |
| EG002 | ACT-541468 5 mg | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules | 0 | 56 | 0 | 56 | 14 | 56 |
| EG003 | ACT-541468 10 mg | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules | 0 | 54 | 0 | 54 | 12 | 54 |
| EG004 | ACT-541468 25 mg | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules | 0 | 55 | 0 | 55 | 10 | 55 |
| EG005 | ACT-541468 50 mg | Each subject participated in 5 treatment periods. On the evening of the first 2 days of each period they received 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 was separated from the next one by a 5- to 12- day washout. ACT-541468: Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg Placebo: Capsules for oral administration matching the ACT-541468 capsules | 0 | 56 | 0 | 56 | 16 | 56 |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Cerumen impaction | Ear and labyrinth disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Defaecation urgency | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
|
| Blood pressure systolic increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
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| Hypochloraemia | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Cerebellar ataxia | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hyporeflexia | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Delusional disorder, unspecified type | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hallucination, visual | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Nasal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
|
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| D001523 |
| Mental Disorders |