Insomnia Disorder, Nocturia
Conditions
Brief summary
A study to find out if daridorexant is safe and efficacious in patients with insomnia and comorbid nocturia
Interventions
DRUGDaridorexant
Daridorexant is available as oral film-coated tablets at a strength of 50 mg.
DRUGPlacebo
Placebo matching daridorexant is provided as identical-looking oral tablets, formulated with the same inactive ingredients (excipients) as the active tablets.
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a multi-center, double-blind, randomized, placebo-controlled, 2-way cross-over post-approval study.
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent form (ICF) prior to any study-mandated procedure. * Male or female subjects ≥ 55 years old at the time of signing the ICF. * Insomnia complaints for at least 3 months prior to Visit 1. * Insomnia Severity Index© (ISI©) score ≥ 13 at Visit 1. * Nocturia severity: on average ≥ 3 nocturnal voids per night reported by the subjects for at least 1 month prior to Visit 1. * Ability to communicate well with the investigator, to understand the study requirements and judged by the investigator to be alert and oriented to person, place, time, and situation.
Exclusion criteria
* Woman of childbearing potential, pregnant or plans to become pregnant. * Planned travel across ≥ 3 time zones during study. * Life time history of suicidality assessed via Columbia Suicide Severity Rating Scale© (C-SSRS©). * Regular caffeine consumption after 4 pm. * Unable to refrain from smoking during the night. * Known and documented diagnosis of narcolepsy, periodic limb movement disorder, moderate to severe obstructive sleep apnea, restless legs syndrome, circadian rhythm sleep-wake disorder, or rapid eye movement (REM) sleep behavior disorder. * Known and documented diagnosis of Type 1 diabetes mellitus, uncontrolled Type 2 diabetes mellitus, central or nephrogenic diabetes insipidus, and primary/secondary polydipsia. * Known and documented nocturia linked to urinary tract infection, neoplasms of bladder, prostate or urethral cancer, bladder or urethral calculi, or neurogenic voiding dysfunction within the last 6 months prior to Visit 1. * Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 4 in sTST | From baseline to Week 4 per treatment period. | Subjective total sleep time (sTST) is the total sleep time reported by the subject in the sleep diary questionnaire. A positive change from baseline indicates an increase in sTST. Baseline is the mean value based on the subject's sleep diary entries for sTST on the 7 days preceding randomization. Week 4 is the mean value based on the subject's sleep diary entries for sTST on study days 23-29 of each treatment period, regardless of premature treatment discontinuations (treatment policy strategy). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 4 in Number of Nocturnal Voids Assessed Using a Voiding Diary | From baseline to Week 4 per treatment period. | The number of nocturnal voids is the total of all nocturnal voids reported by the subject in the voiding diary. Baseline is the mean value based on subject's voiding diary entries for number of nocturnal voids across 3 nights during the screening period. Week 4 is the mean value based on subject's voiding diary entries for number of nocturnal voids across the 3 nights immediately preceding the Week 4 visit of each treatment period, regardless of premature treatment discontinuations (treatment policy strategy). |
Countries
Germany, Spain, United States
Participant flow
Recruitment details
16 sites in 3 countries (USA, Spain and Germany) screened 149 subjects, and 9 sites enrolled (i.e., randomized) at least one subject. Screening started on 18 January 2023 (first subject first visit) and the first subject was enrolled on 16 February 2023.
Pre-assignment details
This study included a screening period of 14-21 days. Subjects who met the inclusion criteria and none of the exclusion criteria were eligible to be enrolled in the study and randomized to one of the two treatment sequences.
Participants by arm
| Arm | Count |
|---|---|
| Daridorexant 50 mg, Then Placebo Subjects first received a daridorexant 50 mg film-coated tablet once daily in the evening within approximately 30 min before going to bed, for 29 (± 2) days.
After a washout period of 14 to 21 days, they then received a placebo film-coated tablet (matching daridorexant 50 mg) once daily in the evening within approximately 30 min before going to bed, for 29 (± 2) days. | 30 |
| Placebo, Then Daridorexant 50 mg Subjects first received a placebo film-coated tablet (matching daridorexant 50 mg) once daily in the evening within approximately 30 min before going to bed, for 29 (± 2) days.
After a washout period of 14 to 21 days, they then received a daridorexant 50 mg film-coated tablet once daily in the evening within approximately 30 min before going to bed, for 29 (± 2) days. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period II | Advice from primary care physician | 1 | 0 |
| Treatment Period II | Private reasons | 0 | 1 |
| Treatment Period II | Subject lost investigational product | 1 | 0 |
| Washout | Forbidden medication | 2 | 0 |
Baseline characteristics
| Characteristic | Daridorexant 50 mg, Then Placebo | Placebo, Then Daridorexant 50 mg | Total |
|---|---|---|---|
| Age, Continuous | 63 years | 63 years | 63 years |
| Number of nocturnal voids | 3.74 Number of nocturnal voids STANDARD_DEVIATION 1.05 | 3.52 Number of nocturnal voids STANDARD_DEVIATION 0.89 | 3.63 Number of nocturnal voids STANDARD_DEVIATION 0.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 10 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 20 Participants | 42 Participants |
| Region of Enrollment Germany | 7 participants | 6 participants | 13 participants |
| Region of Enrollment Spain | 3 participants | 2 participants | 5 participants |
| Region of Enrollment United States | 20 participants | 22 participants | 42 participants |
| Sex: Female, Male Female | 12 Participants | 17 Participants | 29 Participants |
| Sex: Female, Male Male | 18 Participants | 13 Participants | 31 Participants |
| Subjective total sleep time (sTST) | 367.20 minutes STANDARD_DEVIATION 58.6 | 353.17 minutes STANDARD_DEVIATION 54.85 | 360.31 minutes STANDARD_DEVIATION 56.72 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 58 |
| other Total, other adverse events | 6 / 60 | 2 / 58 |
| serious Total, serious adverse events | 0 / 60 | 0 / 58 |
Outcome results
Primary
Change From Baseline to Week 4 in sTST
Subjective total sleep time (sTST) is the total sleep time reported by the subject in the sleep diary questionnaire. A positive change from baseline indicates an increase in sTST. Baseline is the mean value based on the subject's sleep diary entries for sTST on the 7 days preceding randomization. Week 4 is the mean value based on the subject's sleep diary entries for sTST on study days 23-29 of each treatment period, regardless of premature treatment discontinuations (treatment policy strategy).
Time frame: From baseline to Week 4 per treatment period.
Population: The analysis included all randomized subjects who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Daridorexant 50 mg | Change From Baseline to Week 4 in sTST | 56.6 minutes |
| Placebo | Change From Baseline to Week 4 in sTST | 35.7 minutes |
p-value: 0.00295% CI: [8, 33.7]Mixed Models Analysis
Other Pre-specified
Change From Baseline to Week 4 in Number of Nocturnal Voids Assessed Using a Voiding Diary
The number of nocturnal voids is the total of all nocturnal voids reported by the subject in the voiding diary. Baseline is the mean value based on subject's voiding diary entries for number of nocturnal voids across 3 nights during the screening period. Week 4 is the mean value based on subject's voiding diary entries for number of nocturnal voids across the 3 nights immediately preceding the Week 4 visit of each treatment period, regardless of premature treatment discontinuations (treatment policy strategy).
Time frame: From baseline to Week 4 per treatment period.
Population: The analysis included all randomized subjects who received at least one dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daridorexant 50 mg | Change From Baseline to Week 4 in Number of Nocturnal Voids Assessed Using a Voiding Diary | -1.6 number of nocturnal voids | Standard Deviation 1.4 |
| Placebo | Change From Baseline to Week 4 in Number of Nocturnal Voids Assessed Using a Voiding Diary | -1.3 number of nocturnal voids | Standard Deviation 1.3 |