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

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ClinicalTrials.gov Identifier: NCT03679884

Recruitment Status : Completed

First Posted : September 21, 2018

Results First Posted : March 2, 2022

Last Update Posted : March 2, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Idorsia Pharmaceuticals Ltd.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Insomnia Disorder
Interventions	Drug: Daridorexant 10 mg Drug: Daridorexant 25 mg Drug: Daridorexant 50 mg Drug: Placebo
Enrollment	804

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 Details

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 or...	Film-coated tablets administered or...	Film-coated tablets administered or...	Film-coated tablets administered or...	Film-coated tablets administered or...
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 ^[1]	142	268	137	128	126
Completed ^[1]	99	190	93	78	90
Not Completed	43	78	44	50	36
Reason Not Completed
Other	12	12	12	7	8
Lack of Efficacy	15	29	13	29	10
Death	1	0	0	0	0
Adverse Event	2	10	9	6	6
Withdrawal by Subject	12	23	8	8	9
Lost to Follow-up	1	4	2	0	3
[1] DB treatment period

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 or...	Film-coated tablets administered or...	Film-coated tablets administered or...	Film-coated tablets administered or...	Film-coated tablets administered or...	Total of all reporting groups
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 Number of Baseline Participants		142	270	137	128	127	804
Baseline Analysis Population Description		...
Baseline Analysis Population Description		These are the participants included in the FAS. The discrepancy with previous table (Participant Flow) is due to 3 subjects on FAS (2 on daridorexant 25 mg and 1 on ex-placebo/ daridorexant 25 mg) not starting DB treatment.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	142 participants	270 participants	137 participants	128 participants	127 participants	804 participants
	<=18 years	0 0.0%	0 0.0%	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, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	142 participants	270 participants	137 participants	128 participants	127 participants	804 participants
		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 Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	142 participants	270 participants	137 participants	128 participants	127 participants	804 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 ^[1] Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	142 participants	270 participants	137 participants	128 participants	127 participants	804 participants
Black or African American		6 4.2%	19 7.0%	15 10.9%	8 6.3%	7 5.5%	55 6.8%
American Indian or Alaska Native		2 1.4%	0 0.0%	1 0.7%	0 0.0%	0 0.0%	3 0.4%
Native Hawaiian or other Pacific Islander		0 0.0%	0 0.0%	0 0.0%	1 0.8%	0 0.0%	1 0.1%
Asian		5 3.5%	8 3.0%	0 0.0%	2 1.6%	5 3.9%	20 2.5%
White		128 90.1%	243 90.0%	121 88.3%	115 89.8%	115 90.6%	722 89.8%
Other		0 0.0%	0 0.0%	0 0.0%	2 1.6%	0 0.0%	2 0.2%
Not permitted as per legislation/regulation		1 0.7%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.1%
		[1] Measure Description: Race
Race/Ethnicity, Customized ^[1] Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	142 participants	270 participants	137 participants	128 participants	127 participants	804 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%	0 0.0%	0 0.0%
Not permitted as per legislation/regulation		1 0.7%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.1%
		[1] Measure Description: Ethnicity

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 ...
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 or...	Film-coated tablets administered or...	Film-coated tablets administered or...	Film-coated tablets administered or...	Film-coated tablets administered or...
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
Overall Number of Participants Analyzed	142	268	137	128	126
Measure Type: Count of Participants Unit of Measure: Participants
	53 37.3%	103 38.4%	55 40.1%	45 35.2%	48 38.1%

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 or...		Film-coated tablets administered or...		Film-coated tablets administered or...		Film-coated tablets administered or...		Film-coated tablets administered or...
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 (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	1/142 (0.70%)		1/268 (0.37%)		0/137 (0.00%)		0/128 (0.00%)		0/126 (0.00%)
Serious Adverse Events 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 (3.52%)		12/268 (4.48%)		7/137 (5.11%)		2/128 (1.56%)		4/126 (3.17%)
Cardiac disorders
Aortic valve disease mixed ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	0/137 (0.00%)	0	0/128 (0.00%)	0	1/126 (0.79%)	1
Bundle branch block left ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Coronary artery stenosis ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Myocardial infarction ^*	1/142 (0.70%)	1	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Endocrine disorders
Thyroiditis subacute ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	1/137 (0.73%)	1	0/128 (0.00%)	0	0/126 (0.00%)	0
Gastrointestinal disorders
Nausea ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Vomiting ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
General disorders
Chest discomfort ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	0/137 (0.00%)	0	0/128 (0.00%)	0	1/126 (0.79%)	1
Chest pain ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Influenza like illness ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	1/137 (0.73%)	1	0/128 (0.00%)	0	0/126 (0.00%)	0
Infections and infestations
Appendicitis ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	0/137 (0.00%)	0	0/128 (0.00%)	0	1/126 (0.79%)	1
Bronchitis ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Diverticulitis ^*	0/142 (0.00%)	0	2/268 (0.75%)	2	1/137 (0.73%)	1	0/128 (0.00%)	0	0/126 (0.00%)	0
Pneumonia ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	1/137 (0.73%)	1	0/128 (0.00%)	0	0/126 (0.00%)	0
Injury, poisoning and procedural complications
Alcohol poisoning ^*	0/142 (0.00%)	0	1/268 (0.37%)	2	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Head injury ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	0/137 (0.00%)	0	1/128 (0.78%)	1	0/126 (0.00%)	0
Subdural haematoma ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	0/137 (0.00%)	0	1/128 (0.78%)	1	0/126 (0.00%)	0
Wrist fracture ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	1/137 (0.73%)	1	0/128 (0.00%)	0	0/126 (0.00%)	0
Musculoskeletal and connective tissue disorders
Bone disorder ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	1/137 (0.73%)	1	0/128 (0.00%)	0	0/126 (0.00%)	0
Intervertebral disc protrusion ^*	1/142 (0.70%)	1	0/268 (0.00%)	0	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Spinal stenosis ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer ^*	2/142 (1.41%)	2	0/268 (0.00%)	0	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Chronic lymphocytic leukaemia ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	1/137 (0.73%)	1	0/128 (0.00%)	0	0/126 (0.00%)	0
Lung cancer metastatic ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Nervous system disorders
Cerebrovascular accident ^*	1/142 (0.70%)	1	0/268 (0.00%)	0	0/137 (0.00%)	0	0/128 (0.00%)	0	1/126 (0.79%)	1
Lethargy ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Orthostatic intolerance ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Psychiatric disorders
Confusional state ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	1/137 (0.73%)	1	0/128 (0.00%)	0	0/126 (0.00%)	0
Depression ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	0/137 (0.00%)	0	1/128 (0.78%)	1	0/126 (0.00%)	0
Mental status changes ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Suicidal ideation ^*	0/142 (0.00%)	0	0/268 (0.00%)	0	0/137 (0.00%)	0	1/128 (0.78%)	1	0/126 (0.00%)	0
Reproductive system and breast disorders
Ovarian cyst ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary mass ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
Vascular disorders
Arteriosclerosis ^*	0/142 (0.00%)	0	1/268 (0.37%)	1	0/137 (0.00%)	0	0/128 (0.00%)	0	0/126 (0.00%)	0
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	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 (4.93%)		15/268 (5.60%)		12/137 (8.76%)		6/128 (4.69%)		11/126 (8.73%)
Infections and infestations
Nasopharyngitis ^†	7/142 (4.93%)	10	15/268 (5.60%)	16	12/137 (8.76%)	13	6/128 (4.69%)	6	11/126 (8.73%)	11
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Clinical Trial Disclosure Desk
Organization:	Idorsia Pharmaceuticals Ltd
Phone:	+41 58 844 00 00
EMail:	clinical-trials-disclosure@idorsia.com

Layout table for additonal information

Responsible Party:	Idorsia Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:	NCT03679884
Other Study ID Numbers:	ID-078A303
First Submitted:	September 19, 2018
First Posted:	September 21, 2018
Results First Submitted:	January 7, 2022
Results First Posted:	March 2, 2022
Last Update Posted:	March 2, 2022

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