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

Phase 2

Completed

Conditions: Sleep Disorder
Primary Insomnia

Interventions: Drug: placebo
Drug: SKP-1041 (experimental formulation of zaleplon)

Registration Number: NCT00878553

Lead Sponsor: Somnus Therapeutics, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 67

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Two placebo tablets administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence
10 mg SKP-1041	SKP-1041 (experimental formulation of zaleplon)	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
15 mg SKP-1041	SKP-1041 (experimental formulation of zaleplon)	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
20 mg SKP-1041	SKP-1041 (experimental formulation of zaleplon)	Two 10 mg SKP-1041 controlled release zaleplon tablets administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence

Primary Outcome Measures

Name	Time	Method
Wake After Sleep Onset During Hours 3 to 7 Post-dose (WASO 3-7)	Hours 3-7 (inclusive) after tablet ingestion	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.

Secondary Outcome Measures

Name	Time	Method
WASO 1-8	Constantly throughout the 8 hour sleep period	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.
Total Sleep Time 3-7 Hours Post-dose	hours 3-7 (inclusive) post-dose	Total Sleep Time during hours 3-7 (inclusive) post-dose
Number of Awakenings After Sleep Onset During Hours 3 to 7 Post-dose (NAASO 3-7)	hours 3-7 (inclusive) post-dose	Number of Awakenings After Sleep Onset during hours 3-7 post-dose (inclusive) as measured with PSG (polysomnography)
Subjective Wake Time After Sleep Onset (sWASO)	9 hours after tablet ingestion	Subjective wake time after sleep onset sourced from the Morning Sleep Questionnaire self-assessment
Digit Symbol Substitution Test	9 hours after tablet ingestion	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.
Digit Span Test	9 hours post-dose	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.
Visual Analog Scale (Sedation)	9 hours after tablet ingestion	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.
Cmax Pharmacokinetic (PK) Profile Characterization	Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)	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).
Cmax/Dose(Dose-Normalized Cmax)Pharmacokinetic (PK) Profile Characterization	Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)	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).
Tmax Pharmacokinetic (PK) Profile Characterization	Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)	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).
AUC Pharmacokinetic (PK) Profile Characterization	Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)	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).
AUC/Dose (ng*h/mL/mg) Pharmacokinetic (PK) Profile Characterization	Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)	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).
Half-Life (t1/2 Hour) Pharmacokinetic (PK) Profile Characterization	Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)	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).