Study to Assess the Efficacy and Safety of ACT-541468 (Da... | NCT03575104

NCT03575104

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Intervention Names
Daridorexant 10 mg	Experimental	Drug: Daridorexant
Daridorexant 25 mg	Experimental	Drug: Daridorexant
Placebo	Placebo Comparator	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Daridorexant	Drug	Daridorexant will be administered as tablets, orally, once daily in the evening.	Daridorexant 10 mg Daridorexant 25 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Month 1 in Wake After Sleep Onset (WASO) (Sleep Maintenance)	"Wake After Sleep Onset" is the time spent awake after onset of persistent sleep until lights on, as determined by polysomnography.	From baseline to Month 1 (i.e. for up to 1 month)
Change From Baseline to Month 3 in Wake After Sleep Onset (WASO)	"Wake After Sleep Onset" is the time spent awake after onset of persistent sleep until lights on, as determined by polysomnography.	From baseline to Month 3 (i.e. for up to 3 months)
Change From Baseline to Month 1 in Latency to Persistent Sleep (LPS) (Sleep Onset)	"Latency to Persistent Sleep" is the time from start of recording to the beginning of the first continuous 20 epochs (i.e., 10 minutes) scored as non-awake, i.e., epochs scored as either sleep stage 1 (S1), sleep stage 2 (S2), sleep stage 3 (slow wave sleep) or REM, as determined by polysomnography.	From baseline to Month 1 (i.e. for up to 1 month)
Change From Baseline to Month 3 in Latency to Persistent Sleep (LPS)	"Latency to Persistent Sleep" is the time from start of recording to the beginning of the first continuous 20 epochs (i.e., 10 minutes) scored as non-awake, i.e., epochs scored as either sleep stage 1 (S1), sleep stage 2 (S2), sleep stage 3 (slow wave sleep) or REM, as determined by polysomnography.	From baseline to Month 3 (i.e. for up to 3 months)

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Month 1 in the Subjective Total Sleep Time (sTST)	"Subjective Total Sleep Time" is the total sleep time reported by the participant in the sleep diary questionnaire. A positive change from baseline indicates an increase in the subjective Total Sleep Time. A negative change from baseline indicates a decrease in subjective Total Sleep Time.	From baseline to Month 1 (i.e. for up to 1 month)

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Idorsia Pharmaceuticals Ltd.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pulmonary Associates, Pa		Glendale	Arizona	85306	United States
Noble Clinical Research

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33131027	Background	Hudgens S, Phillips-Beyer A, Newton L, Seboek Kinter D, Benes H. Development and Validation of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Patient. 2021 Mar;14(2):249-268. doi: 10.1007/s40271-020-00474-z. Epub 2020 Nov 1.
35065036	Result	Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CLA, Pain S, Kinter DS, Roth T; investigators. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022 Feb;21(2):125-139. doi: 10.1016/S1474-4422(21)00436-1.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
FG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 8, 2018	Jan 5, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
BG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
BG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00057.1± 14.0 BG00156.3± 14.4 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000215 BG001218 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG00017 BG00114 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Black or African American

Title	Measurements
	BG00016 BG00126 BG002

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 From Baseline to Month 1 in Wake After Sleep Onset (WASO) (Sleep Maintenance)

"Wake After Sleep Onset" is the time spent awake after onset of persistent sleep until lights on, as determined by polysomnography.

Posted

Least Squares Mean

95% Confidence Interval

minutes

From baseline to Month 1 (i.e. for up to 1 month)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Units	Counts
Participants	OG000307 OG001309 OG002308

Title

Denominators

Categories

Title	Measurements
	OG000-15.31(-19.531 to -11.087) OG001-24.19(-28.466 to -19.911) OG002-12.57(-16.817 to -8.323)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	Between-treatment analysis for change from baseline in WASO (min) to Month 1 (Daridorexant 25 mg vs placebo).	Mixed Models Analysis	Hypothesis testing result: threshold for significance p = 0.025; statistically significant = YES	0.0001	Mixed effects model for repeated measures: change from baseline in WASO = baseline WASO + age group (< 65; ≥ 65 years) + treatment + visit + treatment × visit + baseline × visit.	LS mean difference to placebo	-11.62			2-Sided	95	-17.604	-5.633					Other

Primary

Change From Baseline to Month 3 in Wake After Sleep Onset (WASO)

"Wake After Sleep Onset" is the time spent awake after onset of persistent sleep until lights on, as determined by polysomnography.

Posted

Least Squares Mean

95% Confidence Interval

minutes

From baseline to Month 3 (i.e. for up to 3 months)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Units	Counts
Participants	OG000

Primary

Change From Baseline to Month 1 in Latency to Persistent Sleep (LPS) (Sleep Onset)

"Latency to Persistent Sleep" is the time from start of recording to the beginning of the first continuous 20 epochs (i.e., 10 minutes) scored as non-awake, i.e., epochs scored as either sleep stage 1 (S1), sleep stage 2 (S2), sleep stage 3 (slow wave sleep) or REM, as determined by polysomnography.

Posted

Least Squares Mean

95% Confidence Interval

minutes

From baseline to Month 1 (i.e. for up to 1 month)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Units	Counts
Participants

Primary

Change From Baseline to Month 3 in Latency to Persistent Sleep (LPS)

Posted

Least Squares Mean

95% Confidence Interval

minutes

From baseline to Month 3 (i.e. for up to 3 months)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Units	Counts
Participants

Secondary

Change From Baseline to Month 1 in the Subjective Total Sleep Time (sTST)

"Subjective Total Sleep Time" is the total sleep time reported by the participant in the sleep diary questionnaire. A positive change from baseline indicates an increase in the subjective Total Sleep Time. A negative change from baseline indicates a decrease in subjective Total Sleep Time.

Posted

Least Squares Mean

95% Confidence Interval

minutes

From baseline to Month 1 (i.e. for up to 1 month)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Units	Counts
Participants

Secondary

Change From Baseline to Month 3 in the Subjective Total Sleep Time (sTST)

Subjective Total Sleep Time is the total sleep time reported by the participant in the sleep diary questionnaire. A positive change from baseline indicates an increase in the subjective Total Sleep Time. A negative change from baseline indicates a decrease in subjective Total Sleep Time.

Posted

Least Squares Mean

95% Confidence Interval

minutes

From baseline to Month 3 (i.e. for up to 3 months)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Units	Counts
Participants

Secondary

Change From Baseline to Month 1 in Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) Sleepiness Domain Score

The Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) is a validated patient reported outcome instrument comprising 14 items (each using a numeric rating scale from 0 to 10) grouped into three domains (i.e., sleepiness, mood, and alert/cognition) reflecting daytime impairment of insomnia. The IDSIQ sleepiness domain has 4 items, and the domain score ranges from 0 to a maximum of 40, where a higher score indicates a greater burden. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

From baseline to Month 1 (i.e. for up to 1 month)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Secondary

Change From Baseline to Month 3 in IDSIQ Sleepiness Domain Score

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

From baseline to Month 3 (i.e. for up to 3 months)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Post-Hoc

Change From Baseline to Month 1 in Log-transformed LPS (LSGM Ratio to Baseline)

Post-hoc analyses were performed using log-transformed LPS data, as the LPS values at baseline more closely resembled a log-normal distribution (skewed to the right) than a normal distribution.

Posted

Geometric Least Squares Mean

95% Confidence Interval

minutes

From baseline to Month 1 (i.e. for up to 1 month)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Units	Counts
Participants

Post-Hoc

Change From Baseline to Month 3 in Log-transformed LPS (LSGM Ratio to Baseline)

Post-hoc analyses were performed using log-transformed LPS data, as the LPS values at baseline more closely resembled a log-normal distribution (skewed to the right) than a normal distribution.

Posted

Geometric Least Squares Mean

95% Confidence Interval

minutes

From baseline to Month 3 (i.e. for up to 3 month)

ID	Title	Description
OG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.
OG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Daridorexant 10 mg	Daridorexant was administered as tablets, orally, once daily in the evening.	306	3	306	49	306
EG001	Daridorexant 25 mg	Daridorexant was administered as tablets, orally, once daily in the evening.	308	3	308	28	308
EG002	Placebo	Matching placebo was administered as tablets, orally, once daily in the evening.	306	4	306	30	306

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertensive crisis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected306 at risk EG0010 events0 affected308 at risk EG0021 events1 affected306 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected306 at risk EG0010 events0 affected308 at risk EG0021 events1 affected306 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected306 at risk EG0010 events0 affected308 at risk EG0021 events1 affected306 at risk
Microvascular coronary artery disease	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected306 at risk EG0010 events0 affected308 at risk EG0020 events0 affected306 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected306 at risk EG0011 events1 affected308 at risk EG0020 events0 affected306 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected306 at risk EG0011 events1 affected308 at risk EG0020 events0 affected306 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected306 at risk EG0010 events0 affected308 at risk EG0020 events0 affected306 at risk
Schizophrenia	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected306 at risk EG0011 events1 affected308 at risk EG0020 events0 affected306 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected306 at risk EG0010 events0 affected308 at risk EG0021 events1 affected306 at risk
Appendicitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected306 at risk EG0010 events0 affected308 at risk EG0020 events0 affected306 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment		EG00019 events14 affected306 at risk EG00116 events16 affected308 at risk EG00212 events11 affected306 at risk
Nasopharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment		EG00041 events38 affected306 at risk EG00115 events13 affected308 at risk EG00222 events20 affected306 at risk

First MCP Posted Date

ID	Term
D007319	Sleep Initiation and Maintenance Disorders

ID	Term
C000634383	daridorexant

The Type I error rate was controlled for the testing of multiple null hypotheses associated with the endpoint assessed at 1 and 3 months of treatment and the two dose levels studied. Each null hypothesis was tested against the alternative hypothesis that daridorexant improved the endpoint at the given dose and time point compared to placebo. The order of testing and the alpha level applied to each null hypothesis was based on the Bonferroni-based gatekeeping procedure (see SAP for details).

OG000307
OG001309
OG002308

OG000307
OG001309
OG002308

OG000307
OG001309
OG002308

OG000307
OG001309
OG002308

Units	Counts
Participants	OG000307 OG001309 OG002308

ID	Term
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases
D001523	Mental Disorders