Chronic Primary Insomnia
Conditions
Keywords
insomnia, elderly, sleeplessness
Brief summary
A 2-night polysomnography / 5-way cross-over study to evaluate the effect, safety and tolerability of oral administration of almorexant (ACT 078573) in elderly subjects with primary insomnia.
Interventions
DRUGACT-078573 oral capsules at 25 and 100 mg and matching placebo
5-period, 5-treatment crossover: sequences: ABECD, BCADE, CDBEA, DECAB, EADBC DCEBA, EDACB, AEBDC, BACED, CBDAE Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo
DRUGACT-078573 and matching placebo
ACT-078573 oral capsules at 25 and 100 mg and matching placebo 5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo
Sponsors
Midnight Pharma, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Elderly subjects (\> 64 years) with a diagnosis of primary insomnia.
Exclusion criteria
* History of any sleep disorder, or any Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) axis I disorder other than primary insomnia. * Sleep apnea, or restless legs syndrome. * Daytime napping of more than 1 hour per day. * Important caffeine consumption, heavy tobacco use, alcohol or drug abuse within 2 years prior to the screening visit. * Unwillingness to refrain from drugs, over-the-counter or herbal medication having an effect on sleep or behavior.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Wake Time After Sleep Onset (WASO) | 2 treatment nights | WASO was the time in minutes scored as wake between the onset of persistent sleep and lights on, where the onset of persistent sleep was the beginning of the first continuous 20 epochs (10 min) scored as non-wake. Mean values were calculated based on 2 treatment PSG nights. PSG nights identified as non-evaluable due to protocol violation were excluded. If a mean value could not be calculated because the value for 1 PSG night was missing or non-evaluable, the valid value for the other PSG night was used. If during a double-blind treatment period a valid PSG was performed but the WASO was missing (e.g., persistent sleep did not occur), the missing value was substituted with the highest value recorded for the subject during the study (single-blind period included). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Total Sleep Time (TST) | 2 treatment nights | TST was the amount of actual sleep time measured in minutes scored as non-wake (i.e., sleep stage 1, 2, slow-wave sleep, or rapid eye movement (sleep)). Mean values were calculated based on 2 treatment PSG nights. PSG nights identified as non-evaluable by protocol violation were excluded. If a mean value could not be calculated because the value for 1 PSG night was missing or non-evaluable, the valid value for the other PSG night was used. If during a double-blind treatment period a valid PSG was performed but the TST was missing (e.g., the subject did not sleep or persistent sleep did not occur), the missing value was substituted with the worst value recorded for the subject during the study (single-blind period included). |
Countries
United States
Participant flow
Recruitment details
242 subjects were screened at 18 centers in the United States and received single-blind placebo treatment. The first subject screening visit was 12 Dec 2007, the first subject was treated on 19 Dec 2007. 112 subjects were randomized, the first assigned double-blind treatment, was on 26 Dec 2007. Last subject, last clinic visit ended on 4 Apr 2008.
Pre-assignment details
The study consisted of a 2-4-week screening phase on single-blind placebo, a 4-8-week treatment phase, and a 28 day safety follow-up. Subjects were randomized to one of 10 treatment sequences.
Participants by arm
| Arm | Count |
|---|---|
| Patient Flow The study consisted of a 2-4-week screening phase (including 2 consecutive screening polysomnography (PSG) nights on single blind placebo), a 4- to 8-week treatment phase, and a 28 day safety follow-up. The treatment phase immediately followed randomization and included 5 treatment periods, each consisting of 2 consecutive treatment PSG nights on the assigned study treatment separated by 5 to 12 days of washout. Subjects were randomized to one of 10 treatment sequences. | 112 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Administrative/Other | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 2 | 1 | 0 |
| Overall Study | Withdrawal of consent | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Patient Flow |
|---|---|
| Age, Continuous | 72.0 years STANDARD_DEVIATION 4.8 |
| Region of Enrollment United States | 112 participants |
| Sex: Female, Male Female | 78 Participants |
| Sex: Female, Male Male | 34 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 112 | 12 / 107 | 12 / 106 | 10 / 106 | 11 / 106 | 10 / 108 |
| serious Total, serious adverse events | 0 / 112 | 1 / 107 | 0 / 106 | 0 / 106 | 0 / 106 | 0 / 108 |
Outcome results
Primary
Mean Wake Time After Sleep Onset (WASO)
WASO was the time in minutes scored as wake between the onset of persistent sleep and lights on, where the onset of persistent sleep was the beginning of the first continuous 20 epochs (10 min) scored as non-wake. Mean values were calculated based on 2 treatment PSG nights. PSG nights identified as non-evaluable due to protocol violation were excluded. If a mean value could not be calculated because the value for 1 PSG night was missing or non-evaluable, the valid value for the other PSG night was used. If during a double-blind treatment period a valid PSG was performed but the WASO was missing (e.g., persistent sleep did not occur), the missing value was substituted with the highest value recorded for the subject during the study (single-blind period included).
Time frame: 2 treatment nights
Population: Number of evaluable patients for this parameter in the per protocol set. Only subjects with all 5 valid values are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Wake Time After Sleep Onset (WASO) | 109.1 minutes | Standard Deviation 36 |
| ACT-078573 25 mg | Mean Wake Time After Sleep Onset (WASO) | 98.7 minutes | Standard Deviation 35.5 |
| ACT-078573 50 mg | Mean Wake Time After Sleep Onset (WASO) | 90.0 minutes | Standard Deviation 35.7 |
| ACT-078573 100 mg | Mean Wake Time After Sleep Onset (WASO) | 77.7 minutes | Standard Deviation 33.2 |
| ACT-078573 200 mg | Mean Wake Time After Sleep Onset (WASO) | 62.6 minutes | Standard Deviation 27.5 |
p-value: 0.001895% CI: [-17, -3.9]Linear model
p-value: <0.000195% CI: [-25.7, -12.6]Linear model
p-value: <0.000195% CI: [-38, -24.9]Linear model
p-value: <0.000195% CI: [-53.3, -39.9]Linear model
Secondary
Mean Total Sleep Time (TST)
TST was the amount of actual sleep time measured in minutes scored as non-wake (i.e., sleep stage 1, 2, slow-wave sleep, or rapid eye movement (sleep)). Mean values were calculated based on 2 treatment PSG nights. PSG nights identified as non-evaluable by protocol violation were excluded. If a mean value could not be calculated because the value for 1 PSG night was missing or non-evaluable, the valid value for the other PSG night was used. If during a double-blind treatment period a valid PSG was performed but the TST was missing (e.g., the subject did not sleep or persistent sleep did not occur), the missing value was substituted with the worst value recorded for the subject during the study (single-blind period included).
Time frame: 2 treatment nights
Population: Number of evaluable patients for this parameter in the per protocol set. Only subjects with all 5 valid values are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Total Sleep Time (TST) | 339.7 minutes | Standard Deviation 43.2 |
| ACT-078573 25 mg | Mean Total Sleep Time (TST) | 353.8 minutes | Standard Deviation 40.1 |
| ACT-078573 50 mg | Mean Total Sleep Time (TST) | 360.9 minutes | Standard Deviation 41.7 |
| ACT-078573 100 mg | Mean Total Sleep Time (TST) | 374.2 minutes | Standard Deviation 39.6 |
| ACT-078573 200 mg | Mean Total Sleep Time (TST) | 394.7 minutes | Standard Deviation 34.6 |
p-value: <0.000195% CI: [7.4, 21.2]Linear model
p-value: <0.000195% CI: [14.6, 28.4]Linear model
p-value: <0.000195% CI: [27.8, 41.6]Linear model
p-value: <0.000195% CI: [48.2, 62]Linear model