Almorexant (ACT-078573) in Elderly Subjects With Chronic Primary Insomnia

Study Overview
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Brief Summary
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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.

Official Title
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Multicenter, Double-blind, Randomized, Placebo-controlled, 5-period, 5-treatment Crossover, Dose-finding Study to Evaluate the Efficacy and Safety of Oral Administration of ACT-078573 in Elderly Subjects With Chronic Primary Insomnia

Conditions
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Chronic Primary Insomnia

Intervention / Treatment
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* Drug: ACT-078573 oral capsules at 25 and 100 mg and matching placebo
* Drug: ACT-078573 and matching placebo
* Drug: ACT-078573 and matching placebo
* Drug: ACT-078573 and matching placebo
* Drug: ACT-078573 and matching placebo
* Drug: ACT-078573 and matching placebo
* Drug: ACT-078573 and matching placebo
* Drug: ACT-078573 and matching placebo
* Drug: ACT-078573 and matching placebo
* Drug: ACT-078573 and matching placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABECD<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 oral capsules at 25 and 100 mg and matching placebo<br>* 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<br>|
| Experimental: BCADE<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|
| Experimental: CDBEA<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|
| Experimental: DECAB<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|
| Experimental: EADBC<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|
| Experimental: DCEBA<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|
| Experimental: EDACB<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|
| Experimental: AEBDC<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|
| Experimental: BACED<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|
| Experimental: CBDAE<br>5-period, 5-treatment crossover Where A = 200mg, B = 100 mg, C = 50 mg, D = 25mg, E = Placebo | Drug: ACT-078573 and matching placebo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 2 treatment nights | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 2 treatment nights | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insomnia, elderly, sleeplessness