Study to Assess the Long Term Safety and Tolerability of ACT-541468 (Daridorexant) in Adult and Elderly Subjects Suffering From Difficulties to Sleep

• Sponsor: Idorsia Pharmaceuticals Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03679884
• Collaborator: (none)
• Enrollment: 804
• Locations: 106
• Arms: 5
• Actual Duration (Months): 28.5
• Patients Per Site: 7.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Study to assess the long term safety and tolerability of daridorexant in adult and elderly subjects suffering from difficulties to sleep

Condition or Disease	Intervention/Treatment	Phase
Insomnia Disorder	Drug: Daridorexant 10 mg; Drug: Daridorexant 25 mg; Drug: Daridorexant 50 mg; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 804 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multi-center, double-blind, parallel-group, randomized, placebo-controlled, three doses, 40-week extension studyMulti-center, double-blind, parallel-group, randomized, placebo-controlled, three doses, 40-week extension study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multi-center, Double-blind, Parallel-group, Randomized, Placebo-controlled, Three Doses, 40-week Extension to Studies ID-078A301 and ID-078A302 to Assess the Long Term Safety and Tolerability of ACT-541468 in Adult and Elderly Subjects With Insomnia Disorder
• Actual Study Start Date: Oct 9, 2018
• Actual Primary Completion Date: Feb 22, 2021
• Actual Study Completion Date: Feb 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daridorexant 10 mg Film-coated tablets administered orally, once daily in the evening	Drug: Daridorexant 10 mg; Daridorexant 10 mg film-coated tablets
Experimental: Daridorexant 25 mg Film-coated tablets administered orally, once daily in the evening	Drug: Daridorexant 25 mg; Daridorexant 25 mg film-coated tablets
Experimental: Daridorexant 50 mg Film-coated tablets administered orally, once daily in the evening	Drug: Daridorexant 50 mg; Daridorexant 50 mg film-coated tablets
Placebo Comparator: Placebo Film-coated tablets administered orally, once daily in the evening	Drug: Placebo; Matching placebo film-coated tablets
Experimental: Ex-Placebo Daridorexant 25 mg Film-coated tablets administered orally, once daily in the evening	Drug: Daridorexant 25 mg; Daridorexant 25 mg film-coated tablets

Outcome Measures

Primary Outcome Measures

1. Total no. of Subjects With at Least One TEAE [TEAEs (AEs that started or worsened during the double-blind study period up to 30 days after double-blind study treatment end date) are reported. Total duration: up to 44 weeks.]

   The primary objective of the study was to assess the long-term safety and tolerability of 10, 25 and 50 mg daridorexant. The total no. of subjects with at least one TEAE is presented here; no statistical analysis was conducted. The full set of safety data is available in the Section "Adverse events".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent prior to any study-mandated procedure (Visit 1).

• Having completed the DB study treatment and the run-out period of ID-078A301 (NCT03545191) or ID-078A302 (NCT03575104).

• For woman of childbearing potential, the following is required:

• Negative urine pregnancy test (EOT of ID-078A301 or ID-078A302 studies)

• Agreement to use the contraception scheme as required by the protocol from Visit 1 up to at least 30 days after EODBT.

Exclusion Criteria:

• Unstable medical condition, significant medical disorder or acute illness, C-SSRS©, ECG, hematology or biochemistry test results in ID-078A301 and ID-078A302, which in the opinion of the investigator could affect the subject's safety or interfere with the study assessments (Visit 1).

• For female subjects: lactating or planning to become pregnant during the duration of the study (Visit 1).

• Positive urine drug test (for benzodiazepines, barbiturates, cannabinoids, opiates, amphetamines, or cocaine) or presence of alcohol in exhaled breath as detected by breathalyzer test (EOT of ID-078A301 or ID-078A302 studies if same day as Visit 1 or Visit 1 if within 7 days after EOT).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pulmonary Associates of the Southeast/WCR	Birmingham	Alabama	United States	35243
2	Pulmonary Associates, Pa	Glendale	Arizona	United States	85306
3	Noble Clinical Research	Tucson	Arizona	United States	85704
4	Preferred Research Partners, Inc	Little Rock	Arkansas	United States	72211
5	Woodland International Research Group	Little Rock	Arkansas	United States	72211
6	Core Healthcare Group	Cerritos	California	United States	90703
7	Marvel Clinical Research	Huntington Beach	California	United States	92647
8	Clinical Trials Research	Lincoln	California	United States	95648
9	Long Beach Clinical Trials	Long Beach	California	United States	90806
10	Artemis Institute For Clinical Research - Riverside	Riverside	California	United States	92503
11	Artemis institute for Clinical Research	San Diego	California	United States	92103
12	Pacific Research Network	San Diego	California	United States	92103
13	Artemis Institute for Clinical Research	San Marcos	California	United States	92078
14	Santa Monica Clinical Trials	Santa Monica	California	United States	90404
15	Empire Clinical Research	Upland	California	United States	91786
16	Innovative Clinical Research	Lafayette	Colorado	United States	80026
17	PAB Clinical Research	Brandon	Florida	United States	33511
18	St. Francis Sleep Allergy and Lung Institute	Clearwater	Florida	United States	33765
19	Clinical Research of South Florida	Coral Gables	Florida	United States	33134
20	Fleming Island Center for Clinical Research	Fleming Island	Florida	United States	32003
21	Research Centers of America	Hollywood	Florida	United States	33024
22	Canvas Clinical Research, LLC	Lake Worth	Florida	United States	33467
23	BioMed Research Institute	Miami	Florida	United States	33126
24	Clinical Research Group of St. Petersburgh	Saint Petersburg	Florida	United States	33707
25	Clinical Site Partners, LLC	Winter Park	Florida	United States	32789
26	Neurotrials Research Incorporated	Atlanta	Georgia	United States	30342
27	Sleep Practitioners, LLC	Macon	Georgia	United States	31210
28	Saltzer Clinical Research	Nampa	Idaho	United States	83686
29	Helene Emsellem, MD	Chevy Chase	Maryland	United States	20815
30	Sleep Disorders Center of the Mid-Atlantic	Glen Burnie	Maryland	United States	21061
31	Infinity Medical Research, Inc.	North Dartmouth	Massachusetts	United States	02747
32	Precise Research Centers	Flowood	Mississippi	United States	39232
33	Barrett Clinic	La Vista	Nebraska	United States	68128
34	Clinical Research Center of Nevada	Las Vegas	Nevada	United States	89104
35	Clinilabs NYC	New York	New York	United States	10019
36	Research Carolina of Hickory	Hickory	North Carolina	United States	28601
37	Research Carolina of Huntersville	Huntersville	North Carolina	United States	28078
38	Coastal Carolina Healthcare	New Bern	North Carolina	United States	28562
39	Wake Research Associates	Raleigh	North Carolina	United States	27604-1547
40	Clinical Trials of America - NC, LLC	Winston-Salem	North Carolina	United States	27103
41	CTI Clinical Research II	Cincinnati	Ohio	United States	45212
42	CTI Clinical Research Center	Cincinnati	Ohio	United States	45255
43	Aventiv Research Inc.	Dublin	Ohio	United States	43016
44	Cleveland Sleep Research Center	Middleburg Heights	Ohio	United States	44130
45	Oregon Center for Clinical Investigations,Inc	Salem	Oregon	United States	97301
46	Brian Abaluck LLC	Paoli	Pennsylvania	United States	19301
47	Omega Medical Research	Warwick	Rhode Island	United States	02886
48	FutureSearch Trials of Neurology, LP	Austin	Texas	United States	78731
49	Inquest Clinical Research	Baytown	Texas	United States	77521
50	InSite Clinical Research	DeSoto	Texas	United States	75115
51	Jacksonville Center for Clinical Research	Jacksonville	Texas	United States	32216
52	Sleep Disorders Centers of the Mid-Atlantic	Vienna	Virginia	United States	22182
53	Swedish Medical Center	Seattle	Washington	United States	98122
54	Hospital UZ Leuven_ Pneumology Department	Leuven		Belgium	3000
55	Acibadem City Clinic Tokuda Hospital EAD	Sofia		Bulgaria	1407
56	Queensway Sleep Lab Sleep Clinic (MedSleep)	Etobicoke		Canada	M9C 5N2
57	The Medical Arts Health Research Group	Kelowna		Canada	V1Y 3G8
58	Somni Research Inc.	Markham		Canada	L3R 1A3
59	CRIUSMQ- CIUSSSCN, CETS (clinique du sommeil)	Quebec		Canada	G1J 2G2
60	CANADIAN PHASE ONWARD INC. (Toronto)	Toronto		Canada	M3J 0K2
61	MedSleep	Toronto		Canada	M4P 1P2
62	Jodha Tishon Inc.	Toronto		Canada	M5G1N8
63	Scan Sleep Specialists	København		Denmark	1053
64	Vitalmed Uniklinikka	Helsinki		Finland	380
65	Oivauni Oy - Kuopio	Kuopio		Finland	70100
66	Oivauni Oy - Tampere	Tampere		Finland
67	Unitutkimusyksikkö, Turun Yliopisto	Turku		Finland
68	CHU NIMES - Unité de Sommeil	Nîmes		France	30029
69	St Hedwig-Krankenhaus, Klinik für Schlaf- und Chronomedizin	Berlin		Germany	10115
70	Klinische Forschung Berlin-Mitte GmbH	Berlin		Germany	10117
71	emovis GmbH	Berlin		Germany	10629
72	Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin Kompetenzzentrum Schlafmedizin	Berlin		Germany	12200
73	Synexus Berlin Research Centre	Berlin		Germany	12627
74	Synexus Clinical Research GmbH	Bochum		Germany	44787
75	Klinische Forschung Dresden GmbH	Dresden		Germany	1069
76	Klinik imd Poliklinik fur Neurochirurgie	Dresden		Germany	1307
77	Synexus Clinical Research GmbH	Frankfurt		Germany	60313
78	Clinical Trial Center North GmbH & Co. KG	Hamburg		Germany	20251
79	Klinische Forschung Hamburg GmbH	Hamburg		Germany	20253
80	Klinische Forschung Hannover Mitte GmbH	Hannover		Germany	30159
81	Klinische Forschung Karlsruhe GmbH	Karlsruhe		Germany	76137
82	Studienzentrum Wilhelmshöhe GmbH	Kassel		Germany	34131
83	Synexus Leipzig Research Centre	Leipzig		Germany	4103
84	Zentrum für Integrative Psychiatrie (ZiP) Universität zu Lübeck	Lübeck		Germany	23538
85	Central Insitute of Mental Health Sleep laboratory Medical Faculty Mannheim/Heidelberg University	Mannheim		Germany	68159
86	Klinikum Rechts der lsar TU München Dept. of Psychiatry and Psychotherapy	München		Germany	81675
87	Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie der Universität am Bezirksklinikum Regensburg	Regensburg		Germany	93053
88	SOMNIBENE Institut für Medizinische Forschung und Schlafmedizin Schwerin GmbH	Schwerin		Germany	19053
89	Kinische Forschung Schwerin GmbH	Schwerin		Germany	19055
90	ZMS Zentrum für medizinische Studien GmbH	Warendorf		Germany	48231
91	Magyar Honvédség Egészségügyi Központ, Neurológiai Osztály	Budapest		Hungary	1134
92	Somnius Kft. SomnoCenter Szeged	Szeged		Hungary	6725
93	4F Neuroimaging analysis laboratory, 56 Dalseong-ro, Jung-gu	Daegu		Korea, Republic of	41931
94	2F Psychiatry Outpatient, 93, Jungbu-daero, Paldal-gu	Suwon		Korea, Republic of	16247
95	PI-House - Centrum Badań Klinicznych	Gdańsk		Poland	80-546
96	Ośrodek Medycyny Study Nurseu Instytutu Psychiatrii i Neurologii (Sleep Disorders Center)	Warsaw		Poland	02-957
97	EMC Instytut Medyczny SA, Przychodnia przy Łowieckiej	Wroclaw		Poland	50220
98	Centro Médico Teknon - Medicina del Sueño	Barcelona		Spain	8017
99	Hospital Universitari Vall d'Hebron - Neurophisiology Deparment - Sleep Unit	Barcelona		Spain	8035
100	Instituto de Investigaciones del Sueno	Madrid		Spain	28036
101	Hospital Universitario Araba - Unidad Funcional de Trastornos del Sueño	Vitoria-Gasteiz		Spain	1004
102	Hospital MAZ - Neurophisiology and Sleep Department	Zaragoza		Spain	50015
103	Göteborgs Universitet, Centrum för sömn och vakenhetsstörningar	Göteborg		Sweden	41390
104	Sömnutredningsmottagningen, smärtcentrum Akademiska sjukhuset	Uppsala		Sweden	75185
105	Universitetssjukhuset Örebro Neurokliniken, Sömnenheten	Örebro		Sweden	70185
106	Zentrum für Schlafmedizin Zürcher Oberland, Zürcher RehaZentrum Wald	Wald		Switzerland	8636

Sponsors and Collaborators

• Idorsia Pharmaceuticals Ltd.

Investigators

• Study Director: Clinical Trials, Idorsia Pharmaceuticals Ltd.

Study Documents (Full-Text)

• Study Protocol: Study Protocol - Feb 17, 2020
• Study Protocol: Study Protocol Addendum - Apr 8, 2020
• Statistical Analysis Plan - Jun 20, 2020

More Information

Publications

None provided.

• Responsible Party: Idorsia Pharmaceuticals Ltd.
• ClinicalTrials.gov Identifier: NCT03679884
• Other Study ID Numbers: ID-078A303
• First Posted: Sep 21, 2018
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders

Study Results

Participant Flow

Recruitment Details

Ninety-four sites in 14 countries (Belgium, Bulgaria, Canada, Denmark, Finland, France, Germany, Hungary, South Korea, Poland, Spain, Sweden, Switzerland, and the US) enrolled and randomized subjects.

Pre-assignment Detail

Subjects assigned to the daridorexant arms in Study ID-078A301 and 302 received the same dose in the ID-078A303 extension study. Subjects assigned to the placebo arm in Study ID-078A301 and 302 were re-randomized to receive either placebo or 25 mg daridorexant in a 1:1 ratio, with treatment allocation stratified by age into 2 categories (< 65 and ≥ 65 years). Note: Subjects' demographic and baseline characteristics were collected in the respective confirmatory 12-week study (ID-078A301 or 302).

Arm/Group Title	Daridorexant 10 mg	Daridorexant 25 mg	Daridorexant 50 mg	Placebo	ExPlacebo/Daridorexant 25 mg
Arm/Group Description	Film-coated tablets administered orally, once daily in the evening Daridorexant 10 mg: Daridorexant 10 mg tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 25 mg: Daridorexant 25 mg tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 50 mg: Daridorexant 50 mg tablets	Film-coated tablets administered orally, once daily in the evening Placebo: Daridorexant matching placebo tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 25 mg: Daridorexant 25 mg tablets
Period Title: Overall Study
STARTED	142	268	137	128	126
COMPLETED	99	190	93	78	90
NOT COMPLETED	43	78	44	50	36

Baseline Characteristics

Arm/Group Title	Daridorexant 10 mg	Daridorexant 25 mg	Daridorexant 50 mg	Placebo	ExPlacebo/Daridorexant 25 mg	Total
Arm/Group Description	Film-coated tablets administered orally, once daily in the evening Daridorexant 10 mg: Daridorexant 10 mg tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 25 mg: Daridorexant 25 mg tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 50 mg: Daridorexant 50 mg tablets	Film-coated tablets administered orally, once daily in the evening Placebo: Daridorexant matching placebo tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 25 mg: Daridorexant 25 mg tablets	Total of all reporting groups
Overall Participants	142	270	137	128	127	804
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	80 56.3%	166 61.5%	83 60.6%	70 54.7%	70 55.1%	469 58.3%
>=65 years	62 43.7%	104 38.5%	54 39.4%	58 45.3%	57 44.9%	335 41.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.6 (12.8)	57.6 (14.1)	56.9 (13.6)	59.2 (12.6)	56.5 (15.5)	57.7 (13.8)
Sex: Female, Male (Count of Participants)
Female	103 72.5%	199 73.7%	98 71.5%	92 71.9%	83 65.4%	575 71.5%
Male	39 27.5%	71 26.3%	39 28.5%	36 28.1%	44 34.6%	229 28.5%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	6 4.2%	19 7%	15 10.9%	8 6.3%	7 5.5%	55 6.8%
American Indian or Alaska Native	2 1.4%	0 0%	1 0.7%	0 0%	0 0%	3 0.4%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%	1 0.8%	0 0%	1 0.1%
Asian	5 3.5%	8 3%	0 0%	2 1.6%	5 3.9%	20 2.5%
White	128 90.1%	243 90%	121 88.3%	115 89.8%	115 90.6%	722 89.8%
Other	0 0%	0 0%	0 0%	2 1.6%	0 0%	2 0.2%
Not permitted as per legislation/regulation	1 0.7%	0 0%	0 0%	0 0%	0 0%	1 0.1%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	6 4.2%	33 12.2%	19 13.9%	10 7.8%	13 10.2%	81 10.1%
Not Hispanic or Latino	135 95.1%	237 87.8%	118 86.1%	118 92.2%	114 89.8%	722 89.8%
Unknown	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not permitted as per legislation/regulation	1 0.7%	0 0%	0 0%	0 0%	0 0%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Total no. of Subjects With at Least One TEAE
Description	The primary objective of the study was to assess the long-term safety and tolerability of 10, 25 and 50 mg daridorexant. The total no. of subjects with at least one TEAE is presented here; no statistical analysis was conducted. The full set of safety data is available in the Section "Adverse events".
Time Frame	TEAEs (AEs that started or worsened during the double-blind study period up to 30 days after double-blind study treatment end date) are reported. Total duration: up to 44 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daridorexant 10 mg	Daridorexant 25 mg	Daridorexant 50 mg	Placebo	ExPlacebo / Daridorexant 25 mg
Arm/Group Description	Film-coated tablets administered orally, once daily in the evening Daridorexant 10 mg: Daridorexant 10 mg tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 25 mg: Daridorexant 25 mg tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 50 mg: Daridorexant 50 mg tablets	Film-coated tablets administered orally, once daily in the evening Placebo: Daridorexant matching placebo tablets	Film-coated tablets administered orally, once daily in the evening Daridorexant 25 mg: Daridorexant 25 mg tablets
Measure Participants	142	268	137	128	126
Count of Participants [Participants]	53 37.3%	103 38.1%	55 40.1%	45 35.2%	48 37.8%

Adverse Events

Time Frame	All treatment-emergent SAEs and AEs are reported.
Adverse Event Reporting Description	TEAEs (AEs that started or worsened during the double-blind study period up to 30 days after double-blind study treatment end date) are reported. Total duration: up to 44 weeks.
Arm/Group Title	Daridorexant 10 mg		Daridorexant 25 mg		Daridorexant 50 mg		Placebo		Ex-Placebo Daridorexant 25 mg
Arm/Group Description	Film-coated tablets administered orally, once daily in the evening Daridorexant 10 mg: Daridorexant 10 mg tablets		Film-coated tablets administered orally, once daily in the evening Daridorexant 25 mg: Daridorexant 25 mg tablets		Film-coated tablets administered orally, once daily in the evening Daridorexant 50 mg: Daridorexant 50 mg tablets		Film-coated tablets administered orally, once daily in the evening Placebo: Daridorexant matching placebo tablets		Film-coated tablets administered orally, once daily in the evening Daridorexant 25 mg: Daridorexant 25 mg tablets
All Cause Mortality
	Daridorexant 10 mg		Daridorexant 25 mg		Daridorexant 50 mg		Placebo		Ex-Placebo Daridorexant 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/142 (0.7%)		1/268 (0.4%)		0/137 (0%)		0/128 (0%)		0/126 (0%)
Serious Adverse Events
	Daridorexant 10 mg		Daridorexant 25 mg		Daridorexant 50 mg		Placebo		Ex-Placebo Daridorexant 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/142 (3.5%)		12/268 (4.5%)		7/137 (5.1%)		2/128 (1.6%)		4/126 (3.2%)
Cardiac disorders
Aortic valve disease mixed	0/142 (0%)	0	0/268 (0%)	0	0/137 (0%)	0	0/128 (0%)	0	1/126 (0.8%)	1
Bundle branch block left	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Coronary artery stenosis	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Myocardial infarction	1/142 (0.7%)	1	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Endocrine disorders
Thyroiditis subacute	0/142 (0%)	0	0/268 (0%)	0	1/137 (0.7%)	1	0/128 (0%)	0	0/126 (0%)	0
Gastrointestinal disorders
Nausea	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Vomiting	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
General disorders
Chest discomfort	0/142 (0%)	0	0/268 (0%)	0	0/137 (0%)	0	0/128 (0%)	0	1/126 (0.8%)	1
Chest pain	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Influenza like illness	0/142 (0%)	0	0/268 (0%)	0	1/137 (0.7%)	1	0/128 (0%)	0	0/126 (0%)	0
Infections and infestations
Appendicitis	0/142 (0%)	0	0/268 (0%)	0	0/137 (0%)	0	0/128 (0%)	0	1/126 (0.8%)	1
Bronchitis	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Diverticulitis	0/142 (0%)	0	2/268 (0.7%)	2	1/137 (0.7%)	1	0/128 (0%)	0	0/126 (0%)	0
Pneumonia	0/142 (0%)	0	0/268 (0%)	0	1/137 (0.7%)	1	0/128 (0%)	0	0/126 (0%)	0
Injury, poisoning and procedural complications
Alcohol poisoning	0/142 (0%)	0	1/268 (0.4%)	2	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Head injury	0/142 (0%)	0	0/268 (0%)	0	0/137 (0%)	0	1/128 (0.8%)	1	0/126 (0%)	0
Subdural haematoma	0/142 (0%)	0	0/268 (0%)	0	0/137 (0%)	0	1/128 (0.8%)	1	0/126 (0%)	0
Wrist fracture	0/142 (0%)	0	0/268 (0%)	0	1/137 (0.7%)	1	0/128 (0%)	0	0/126 (0%)	0
Musculoskeletal and connective tissue disorders
Bone disorder	0/142 (0%)	0	0/268 (0%)	0	1/137 (0.7%)	1	0/128 (0%)	0	0/126 (0%)	0
Intervertebral disc protrusion	1/142 (0.7%)	1	0/268 (0%)	0	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Spinal stenosis	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	2/142 (1.4%)	2	0/268 (0%)	0	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Chronic lymphocytic leukaemia	0/142 (0%)	0	0/268 (0%)	0	1/137 (0.7%)	1	0/128 (0%)	0	0/126 (0%)	0
Lung cancer metastatic	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/142 (0.7%)	1	0/268 (0%)	0	0/137 (0%)	0	0/128 (0%)	0	1/126 (0.8%)	1
Lethargy	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Orthostatic intolerance	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Psychiatric disorders
Confusional state	0/142 (0%)	0	1/268 (0.4%)	1	1/137 (0.7%)	1	0/128 (0%)	0	0/126 (0%)	0
Depression	0/142 (0%)	0	0/268 (0%)	0	0/137 (0%)	0	1/128 (0.8%)	1	0/126 (0%)	0
Mental status changes	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Suicidal ideation	0/142 (0%)	0	0/268 (0%)	0	0/137 (0%)	0	1/128 (0.8%)	1	0/126 (0%)	0
Reproductive system and breast disorders
Ovarian cyst	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary mass	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Vascular disorders
Arteriosclerosis	0/142 (0%)	0	1/268 (0.4%)	1	0/137 (0%)	0	0/128 (0%)	0	0/126 (0%)	0
Other (Not Including Serious) Adverse Events
	Daridorexant 10 mg		Daridorexant 25 mg		Daridorexant 50 mg		Placebo		Ex-Placebo Daridorexant 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/142 (4.9%)		15/268 (5.6%)		12/137 (8.8%)		6/128 (4.7%)		11/126 (8.7%)
Infections and infestations
Nasopharyngitis	7/142 (4.9%)	10	15/268 (5.6%)	16	12/137 (8.8%)	13	6/128 (4.7%)	6	11/126 (8.7%)	11

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any study-related publication written independently by investigators must be submitted to Idorsia for review at least 30 days prior to submission for publication or presentation at a congress. Upon review, Idorsia may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights. Neither the institution nor the investigator should permit publication during such a review period.