Insomnia Disorder
Conditions
Brief summary
Study to assess the long term safety and tolerability of daridorexant in adult and elderly subjects suffering from difficulties to sleep
Interventions
Daridorexant 10 mg film-coated tablets
Daridorexant 25 mg film-coated tablets
Daridorexant 50 mg film-coated tablets
DRUGPlacebo
Matching placebo film-coated tablets
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Multi-center, double-blind, parallel-group, randomized, placebo-controlled, three doses, 40-week extension study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium, Bulgaria, Canada, Denmark, Finland, France, Germany, Hungary, Poland, South Korea, Spain, Sweden, Switzerland, United States
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).
Participants by arm
| Arm | Count |
|---|---|
| Daridorexant 10 mg Film-coated tablets administered orally, once daily in the evening
Daridorexant 10 mg: Daridorexant 10 mg tablets | 142 |
| Daridorexant 25 mg Film-coated tablets administered orally, once daily in the evening
Daridorexant 25 mg: Daridorexant 25 mg tablets | 270 |
| Daridorexant 50 mg Film-coated tablets administered orally, once daily in the evening
Daridorexant 50 mg: Daridorexant 50 mg tablets | 137 |
| Placebo Film-coated tablets administered orally, once daily in the evening
Placebo: Daridorexant matching placebo tablets | 128 |
| ExPlacebo/Daridorexant 25 mg Film-coated tablets administered orally, once daily in the evening
Daridorexant 25 mg: Daridorexant 25 mg tablets | 127 |
| Total | 804 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 10 | 9 | 6 | 6 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 15 | 29 | 13 | 29 | 10 |
| Overall Study | Lost to Follow-up | 1 | 4 | 2 | 0 | 3 |
| Overall Study | Other | 12 | 12 | 12 | 7 | 8 |
| Overall Study | Withdrawal by Subject | 12 | 23 | 8 | 8 | 9 |
Baseline characteristics
| Characteristic | Daridorexant 50 mg | Placebo | Daridorexant 10 mg | ExPlacebo/Daridorexant 25 mg | Total | Daridorexant 25 mg |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 54 Participants | 58 Participants | 62 Participants | 57 Participants | 335 Participants | 104 Participants |
| Age, Categorical Between 18 and 65 years | 83 Participants | 70 Participants | 80 Participants | 70 Participants | 469 Participants | 166 Participants |
| Age, Continuous | 56.9 years STANDARD_DEVIATION 13.6 | 59.2 years STANDARD_DEVIATION 12.6 | 58.6 years STANDARD_DEVIATION 12.8 | 56.5 years STANDARD_DEVIATION 15.5 | 57.7 years STANDARD_DEVIATION 13.8 | 57.6 years STANDARD_DEVIATION 14.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 5 Participants | 5 Participants | 20 Participants | 8 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 8 Participants | 6 Participants | 7 Participants | 55 Participants | 19 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 19 Participants | 10 Participants | 6 Participants | 13 Participants | 81 Participants | 33 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 118 Participants | 118 Participants | 135 Participants | 114 Participants | 722 Participants | 237 Participants |
| Race/Ethnicity, Customized Not permitted as per legislation/regulation | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 121 Participants | 115 Participants | 128 Participants | 115 Participants | 722 Participants | 243 Participants |
| Sex: Female, Male Female | 98 Participants | 92 Participants | 103 Participants | 83 Participants | 575 Participants | 199 Participants |
| Sex: Female, Male Male | 39 Participants | 36 Participants | 39 Participants | 44 Participants | 229 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 142 | 1 / 268 | 0 / 137 | 0 / 128 | 0 / 126 |
| other Total, other adverse events | 7 / 142 | 15 / 268 | 12 / 137 | 6 / 128 | 11 / 126 |
| serious Total, serious adverse events | 5 / 142 | 12 / 268 | 7 / 137 | 2 / 128 | 4 / 126 |
Outcome results
Primary
Total no. of Subjects With at Least One TEAE
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daridorexant 10 mg | Total no. of Subjects With at Least One TEAE | 53 Participants |
| Daridorexant 25 mg | Total no. of Subjects With at Least One TEAE | 103 Participants |
| Daridorexant 50 mg | Total no. of Subjects With at Least One TEAE | 55 Participants |
| Placebo | Total no. of Subjects With at Least One TEAE | 45 Participants |
| ExPlacebo / Daridorexant 25 mg | Total no. of Subjects With at Least One TEAE | 48 Participants |