Study of Sleep-maintenance Activity of 3 Doses of SKP-1041

Study Overview
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Brief Summary
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SKP-1041 is a new formulation of a marketed sleeping agent called zaleplon. Zaleplon is currently available as Sonata as well as several generic formulations. Sonata and its generics induce sleep soon after ingestion. SKP-1041, however, is a formulation that is designed to become active 2-3 hours after ingestion. It is intended for use in people who have no trouble falling to sleep but who often awaken in the middle of the night. This trial will determine the best dose to prevent those awakenings.

Detailed Description
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Patients will participate in the study for approximately 44 to 56 days, including a 14- to 21-day Screening Period, 4 Treatment Periods each followed by washout periods, and a final Follow-up Visit. Patients will receive their randomly assigned study medication and spend 2 nights in a sleep laboratory, subsequently returning home for a 4- to 7-day washout period between each treatment period. The fourth and final treatment period will include a third night at the site during which all patients will continue to receive the same study medication as on the first 2 nights of this treatment period. Blood will be drawn from all patients for pharmacokinetic analyses at specific time intervals. Patients will undergo final safety assessments 2 to 5 days after the last dose of study medication.

Official Title
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A Phase 2, Double-Blind, Placebo-Controlled, Double-Dummy, Cross-Over Study to Investigate the Hypnotic Activity of Three Doses (10mg, 15mg, 20mg) of a New Zaleplon Prototype, SKP-1041, in Adults With Primary Insomnia

Conditions
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Sleep Disorder, Primary Insomnia

Intervention / Treatment
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* Drug: placebo
* Drug: SKP-1041 (experimental formulation of zaleplon)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary insomnia characterized by chronic difficulty maintaining sleep Exclusion Criteria: History of restless legs syndrome, sleep apnea, narcolepsy, or parasomnias; Any clinically relevant acute or chronic diseases which could interfere with the patient's safety during this trial or with this tablet's absorption; Pregnancy; History of medication allergies; Use of medication that might interfere with this study; Recent travel across more than 3 time zones.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 64 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Two placebo tablets administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence | Drug: placebo<br>* tablet at bedtime<br>* Other names: sugar pill;|
| Experimental: 10 mg SKP-1041<br>One 10 mg SKP-1041 controlled release zaleplon tablet plus one placebo tablet administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence | Drug: SKP-1041 (experimental formulation of zaleplon)<br>* tablet at bedtime<br>* Other names: zaleplon;|
| Experimental: 15 mg SKP-1041<br>One 15 mg SKP-1041 controlled release zaleplon tablet plus one placebo tablet administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence | Drug: SKP-1041 (experimental formulation of zaleplon)<br>* tablet at bedtime<br>* Other names: zaleplon;|
| Experimental: 20 mg SKP-1041<br>Two 10 mg SKP-1041 controlled release zaleplon tablets administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence | Drug: SKP-1041 (experimental formulation of zaleplon)<br>* tablet at bedtime<br>* Other names: zaleplon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wake After Sleep Onset During Hours 3 to 7 Post-dose (WASO 3-7) | Wake time After Sleep Onset hours 3-7 Pairwise comparisons of treatment group vs. placebo mean change from baseline in minutes per polysomnographic recording. Each patient receives baseline placebo and then each treatment dose at bedtime for two nights of sleep laboratory PSG measurements. The WASO3-7 mean of each two night visit is then used to compare placebo vs. treatment change from baseline minutes awake during hours 3 through 7 post-dose. | Hours 3-7 (inclusive) after tablet ingestion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WASO 1-8 | Wake Time After Sleep Onset, measured in minutes over the full 8 hour polysomnographic recording period, is summarized by treatment group for each night during the Screening and Treatment Periods. | Constantly throughout the 8 hour sleep period | 
| Total Sleep Time 3-7 Hours Post-dose | Total Sleep Time during hours 3-7 (inclusive) post-dose | hours 3-7 (inclusive) post-dose | 
| Number of Awakenings After Sleep Onset During Hours 3 to 7 Post-dose (NAASO 3-7) | Number of Awakenings After Sleep Onset during hours 3-7 post-dose (inclusive) as measured with PSG (polysomnography) | hours 3-7 (inclusive) post-dose | 
| Subjective Wake Time After Sleep Onset (sWASO) | Subjective wake time after sleep onset sourced from the Morning Sleep Questionnaire self-assessment | 9 hours after tablet ingestion | 
| Digit Symbol Substitution Test | Assessment of next-day residual cognitive effects. The Digit Symbol Substitution Test (DSST) explores attention and psychomotor speed. Given a code table displaying the correspondence between pairs of digits (from 1 to 9) and symbols, the patient filled in blank squares with the symbol that was paired with the digit displayed above the square. The patient was required to fill in as many squares as possible in 180 seconds. | 9 hours after tablet ingestion | 
| Digit Span Test | Assessment of next day residual cognitive effects via testing immediate recall of numbers. The patient was given a string of digits and asked to repeat them forward, and then a second string of digits to repeat backward. The score was the number of correct responses, where the digits were repeated correctly. One point was given for each correctly repeated string of digits. The maximum subscore in the Digits Forward was 16, and the maximum subscore in the Digits Backward was 14, for a total score of 30. | 9 hours post-dose | 
| Visual Analog Scale (Sedation) | Self-assessment of next morning sedation. Patients answered the question How alert do you feel? via a 100mm scale on which 0mm indicated very sleepy and 100mm indicated wide awake and alert.The VAS measures a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. Operationally, a VAS is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end (in this case, sleepiness and alertness). Patients were asked to mark the point on the line that they felt represented their current state. The VAS score was determined by measuring in millimeters from the left-hand end of the line to the point that the patient marked. | 9 hours after tablet ingestion | 
| Cmax Pharmacokinetic (PK) Profile Characterization | A detailed characterization of the Cmax (maximum plasma concentration of SKP-1041 zaleplon in ng/mL) for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses. Descriptive statistics and analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis). | Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) | 
| Cmax/Dose(Dose-Normalized Cmax)Pharmacokinetic (PK) Profile Characterization | A detailed characterization of Cmax/Dose (ng/mL/mg) (maximum plasma zaleplon concentration normalized per dose) PK profile of SKP-1041 zaleplon for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses. Descriptive statistics, geometric means and 90% confidence intervals were calculated for dose-normalized values of Cmax. Analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis). | Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) | 
| Tmax Pharmacokinetic (PK) Profile Characterization | A detailed characterization of Tmax (hour) (timepoint post-dose of maximum plasma zaleplon concentration) PK profile of SKP-1041 zaleplon for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses. Descriptive statistics and analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis). | Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) | 
| AUC Pharmacokinetic (PK) Profile Characterization | A detailed characterization of the AUC (area under the concentration-time curve of SKP-1041 zaleplon) for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses. Descriptive statistics were calculated for AUC. Analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis). | Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) | 
| AUC/Dose (ng*h/mL/mg) Pharmacokinetic (PK) Profile Characterization | A detailed characterization of the AUC/Dose (ng*h/mL/mg) [Area under the concentration-time curve per Dose of SKP-1041 zaleplon] for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses. Descriptive statistics and analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis). | Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) | 
| Half-Life (t1/2 Hour) Pharmacokinetic (PK) Profile Characterization | A detailed characterization of the plasma Half-Life (t1/2 in hours) of SKP-1041 zaleplon the each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses. Descriptive statistics and analysis of variance (ANOVA)for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis). | Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insomnia, middle of the night, sleep maintenance