A Polysomnographic Study to Compare the Efficacy of Gastric Retentive Zaleplon Accordion Pill to Placebo in Subjects With Insomnia

Study Overview
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Brief Summary
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This is a multi center, double blind placebo controlled, two-way crossover study in patients with Insomnia suffering from difficulty in falling asleep and staying asleep. This study intends to assess the efficacy of Zaleplon AP in improving sleep parameters, comparing to placebo.

Official Title
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Double Blind, Polysomnographic, Two-Way Crossover Study To Compere The Efficacy Of Gastric Retentive Zaleplon (Zaleplon AP) To Placebo In Subjects With Insomnia Characterized By Both Difficulty In Falling Asleep And Staying Asleep

Conditions
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Insomnia

Intervention / Treatment
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* Drug: Zaleplon AP formulation
* Drug: Placebo capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects between the ages of 18 and 65 years of age Subjects that meet DSM IV diagnostic criteria for Primary Insomnia Subjects that report a time in bed ≥6.5 and ≤9 hours Subjects that report on a one week sleep diary (on at least 3 of 7 nights) TST ≤6.5 hours Subjects that report on a one week sleep diary (on at least 3 of 7 nights)Wake time after sleep >1.0 hour Subjects that report on a one week sleep diary (on at least 3 of 7 nights) ≥30 minutes time to sleep onset On two nights of PSG screening a mean WASO of ≥60 minutes with neither night less than 45 minutes On two nights of PSG screening a mean LPS of ≥20 minutes with neither night less than 15 minutes On two nights of PSG screening a TST of ≤6.5 hours on each of the two nights Body mass index of 18 - 34 inclusive Subjects that report a median habitual bedtime between 9:00pm (21:00 hours) and 12:00am (00:00) on a one week sleep diary (based on 3 or more nights). Exclusion Criteria: Participation in another drug clinical trial within 1 month prior to first screening diary day (calculated from the previous study's last dosing date). On screening PSG night 1 an AHI >10 (apnea hypopnea index) On screening PSG night 1 a PLMAI ≥10 (periodic limb movements with arousal) Subject has a circadian rhythm disorder including shift work or the need to travel ≥3 time zones during the course of the study Subject has any other sleep disorder (e.g. Restless Legs Syndrome ) Use of any drug known to effect sleep or wake functions within 5 half lives of the drug or two weeks, whichever comes first. Subject with a history (past year) of alcohol or substance abuse Subject that needs to smoke during the sleep period time Subject that reports habitual napping (more than 3 times per week) Subject has currently or a significant history of seizures, sleep apnea or restless leg syndrome or other sleep disorders which, in the opinion of the investigator responsible, contraindicates his/her participation Subjects with a recent history of clinically defined GERD, peptic ulcer or any gastrointestinal surgery other than appendectomy or herniotomy which, in the opinion of the investigator responsible, contraindicates his/her participation Subject with any gastrointestinal disorder likely to influence drug absorption, or with any history of inflammatory bowel disease, intestinal obstruction, irritable bowel syndrome, severe gastrointestinal narrowing, or frequent nausea or emesis, regardless of etiology which, in the opinion of the investigator responsible, contraindicates his/her participation Subjects suffering from any Axis 1 Psychiatric Disorder that in the opinion of the investigator responsible may interfere with full participation Subject has significant history of cardiac, pulmonary, hepatic or renal disease or other condition or any major complication/illness which, in the opinion of the investigator responsible, contraindicates his/her participation. The subject has any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator Subject is taking CNS-active drugs (including herbal products with CNS effects), known to affect the sleep/wake cycle including but not limited to anxiolytic, hypnotics, antidepressants, sedating H1 antihistamines, systemic steroids, anticonvulsants, narcotic analgesics, respiratory stimulants respiratory decongestants, OTC and prescription diet aids, OTC and prescription stimulants, St. John's Wort, and melatonin. Females who are pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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: Zaleplon AP formulation<br>Gastric Retentive Dual Release Zaleplon (Zaleplon AP) | Drug: Zaleplon AP formulation<br>* Gastric retentive dual release Zaleplon<br>|
| Placebo Comparator: Placebo<br>Identical placebo capsule | Drug: Placebo capsule<br>* Identical placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of dual release Zaleplon (Zaleplon AP) on Total Sleep Time (TST) | The change from baseline on the mean of drug nights 1 and 2 relative to placebo. | Polysomnography tests for 2 consecutive nights at each treatment arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the efficacy of Zaleplon AP on Latency to Persistent Sleep (LPS) | The change from baseline on the mean of drug nights 1 and 2 relative to placebo. | Polysomnography tests for 2 consecutive nights at each treatment arm | 
| To determine the efficacy of Zaleplon AP on Wake time After Sleep Onset (WASO) | The change from baseline on the mean of drug nights 1 and 2 relative to placebo. | Polysomnography tests for 2 consecutive nights at each treatment arm | 
| To evaluate the presence of any residual effects using the digital symbol substitution test (DSST) and a memory test | The change from baseline on the mean of drug nights 1 and 2 relative to placebo. | 2 consecutive mornings at each treatment arm | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSG, LPS, TST, WASO, Subjects With Insomnia characterized by both Difficulty in Falling Asleep and Staying Asleep