Study of Sleep-maintenance Activity of 3 Doses of SKP-1041 | NCT00878553

Name	Class
INC Research Limited	INDUSTRY

Study of Sleep-maintenance Activity of 3 Doses of SKP-1041 | NCT00878553 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Two placebo tablets administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence	Drug: placebo
10 mg SKP-1041	Experimental	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)
15 mg SKP-1041	Experimental	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)
20 mg SKP-1041	Experimental	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)

Name	Type	Description	Arm Group Labels	Other Names
placebo	Drug	tablet at bedtime	Placebo	sugar pill

Outcomes Module

Primary Outcomes

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 Outcomes

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

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Jon Freeman, PhD	Clinilabs, Inc.	Principal Investigator
Steven G. Hull, MD	Vince and Associates Clinical Research	Principal Investigator
Russell Rosenberg, PhD	Neurotrials Inc.	Principal Investigator
James K. Walsh, PhD	Sleep Medicine and Research Center	Principal Investigator
David J. Seiden, MD	Broward Research Group	Principal Investigator
Helene A. Emsellem, MD	Emsellem MD PC	Principal Investigator
D. Alan Lankford, PhD	Sleep Disorders Center of Georgia	Principal Investigator
Beth E. Safirstein, MD	MD Clinical	Principal Investigator

Arm/Group Information

ID	Title	Description
FG000	Baseline: All Randomized Patients	The second screening visit consisted of 2 consecutive sleep laboratory nights of placebo pretreatment and full PSG recordings. The 67 patients who met entry criteria were then randomized to four treatment sequences with their screening night mean PSG parameters defined as their baseline. This trial was comprised of 2 study periods: Sleep and Pharmacokinetic (PK). Each of 67 patients was randomly assigned a sequence of the four treatment arms, washed out, and then crossed over to the next assigned treatment in their sequence for the Sleep Study. For each of these treatment arms, two "double-dummy" tablets were administered at bedtime for two consecutive nights. An additional (third) dosing night allowed for pharmacokinetic characterization of the investigational zaleplon formulation. In this PK Substudy, patient's plasma concentrations were measured after a single dose in parallel group design.
FG001	Placebo (Sugar Pill)	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo treatment. Two placebo tablets were administered orally at bedtime for two consecutive nights during the Sleep Study, after which patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned for the next treatment in their randomized sequence.
FG002	10 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 10mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 10 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
FG003	15 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 15mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 15 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
FG004	20 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 20mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two 10 mg SKP-1041 tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Periods

Title

Milestones

Reasons Not Completed

Sleep Study

Type	Comment	Milestone Data
STARTED		FG00067 subjectsThis Intention to Treat population includes all randomized patients; one dropped prior to treatment. FG0010 subjects FG0020 subjects FG0030 subjects FG0040 subjects
Number of Patients Receiving Placebo		FG00066 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Number of Patients Receiving 10mg		FG00065 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Number of Patients Receiving 15mg		FG00065 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Number of Patients Receiving 20mg		FG00065 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
COMPLETED		FG00062 subjects5 patient withdraws result in greater than 5 lost patient data across groups due to CROSSOVER design FG0010 subjects FG0020 subjects FG003
NOT COMPLETED		FG0005 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Type	Comment	Reasons
Withdrawal by Subject		FG0002 subjects FG0010 subjects FG0020 subjects FG003

PK Study

Type	Comment	Milestone Data
STARTED		FG0000 subjectsA total of 62 randomized patients started this parallel group, single dose PK substudy. FG00116 subjectsDuring the PK period, 16 randomized participants received one bedtime dose of SKP-1041 placebo. FG00217 subjectsDuring the PK period, 17 randomized participants received one bedtime dose of 10mg SKP-1041. FG003

Baseline Characteristics Module

ID	Title	Description
BG000	Sequence 1	10mg SKP-1041, 15mg SKP-1041, Placebo, 20mg SKP-1041
BG001	Sequence 2	Placebo, 10mg SKP-1041, 20mg SKP-1041, 15mg SKP-1041

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Efficacy analyses were performed on the Intention to Treat Population(all randomized patients).

Posted

Mean

Standard Error

minutes

Hours 3-7 (inclusive) after tablet ingestion

ID	Title	Description
OG000	Placebo (Sugar Pill)	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo treatment in place of the investigational zaleplon delayed and sustained release SKP-1041 tablets. These patients received two placebo tablets orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Each of the 67 patients was randomly assigned a sequence of the four treatment arms, washed out, and then crossed over to the next assigned treatment in their sequence.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Headache	Nervous system disorders	MedDRA 12.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Dr. Christine Blumhardt, Chief Regulatory Officer	Somnus Therapeutics, Inc	617-710-0928		cblumhardt@somnusthera.com

Condition Browse Module

ID	Term
D012893	Sleep Wake Disorders
D007319	Sleep Initiation and Maintenance Disorders

ID	Term
D009422	Nervous System Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000073893	Sugars
C085665	zaleplon

ID	Term
D002241	Carbohydrates

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Literature-based estimates of WASO (Wake After Sleep Onset) SD (Standard Deviation) range from 39 to 45 minutes. Null hypothesis: difference between mean WASO3-7 values for placebo and the 15-mg SKP-1041 dose level equals 0. By using a 2-sided, 1-sample t test at the 5% level of significance of this null hypothesis and an assumed SD of 45 minutes, a sample size of 54 completed patients was calculated to provide 90% power to detect a mean treatment difference of 20 minutes	Mixed Models Analysis	This hierarchical, 2-sided testing procedure maintained the overall level of significance at approximately 0.05	0.0118	Change from baseline in mean WASO3-7 compared values for the 20-mg dose vs. placebo. If that comparison demonstrated superiority of the 20-mg dose, then results for the 15-mg dose vs. placebo were compared; if significant, then 10-mg vs. placebo	Mean Difference (Net)	-8.606	Standard Error of the Mean	2.420	2-Sided	95	-15.284	-1.927	Adjusted mean differences were analyzed via general linear model that used change from baseline as response variable and included effects for patient, period, sequence, and treatment. A negative mean change from baseline indicates an improvement.	No	Superiority or Other
OG000 OG002	Literature-based estimates of WASO SD range from 39 to 45 minutes. Null hypothesis: difference between mean WASO3-7 values for placebo and the 15-mg SKP-1041 dose level equals 0. By using a 2-sided, 1-sample t test at the 5% level of significance of this null hypothesis and an assumed SD of 45 minutes, a sample size of 54 completed patients was calculated to provide 90% power to detect a mean treatment difference of 20 minutes	Mixed Models Analysis	This hierarchical, 2-sided testing procedure maintained the overall level of significance at approximately 0.05	0.0037	Change from baseline in mean WASO3-7 compared values for the 20-mg dose vs. placebo. If that comparison demonstrated superiority of the 20-mg dose, then results for the 15-mg dose vs. placebo were compared; if significant, then 10-mg vs. placebo	Mean Difference (Net)	-9.98	Standard Error of the Mean	2.421	2-Sided	95	-16.685	-3.275	Adjusted mean differences were analyzed via general linear model that used change from baseline as response variable and included effects for patient, period, sequence, and treatment. A negative mean change from baseline indicates an improvement	No	Superiority or Other
OG000 OG003	Literature-based estimates of WASO SD range from 39 to 45 minutes. Null hypothesis: difference between mean WASO3-7 values for placebo and the 20-mg SKP-1041 dose level equals 0. By using a 2-sided, 1-sample t test at the 5% level of significance of this null hypothesis and an assumed SD of 45 minutes, a sample size of 54 completed patients was calculated to provide 90% power to detect a mean treatment difference of 20 minutes.	Mixed Models Analysis	This hierarchical, 2-sided testing procedure maintained the overall level of significance at approximately 0.05.	0.0077	Change from baseline in mean WASO3-7 compared values for the 20-mg dose vs. placebo. If that comparison demonstrated superiority of the 20-mg dose, then results for the 15-mg dose vs. placebo were compared; if significant, then 10-mg vs. placebo.	Mean Difference (Net)	-9.153	Standard Error of the Mean	2.422	2-Sided	95	-15.857	-2.448	Adjusted mean differences were analyzed via general linear model that used change from baseline as response variable and included effects for patient, period, sequence, and treatment. A negative mean change from baseline indicates an improvement	No	Superiority or Other

Secondary

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.

Intention to Treat population

Posted

Mean

Standard Error

Minutes

Constantly throughout the 8 hour sleep period

ID	Title	Description
OG000	Placebo	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo in place of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two placebo tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG001	10 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 10mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 10 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG002	15 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 15mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 15 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG003	20 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 20mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two 10 mg SKP-1041 tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Units	Counts
Participants	OG00067 OG00167 OG00267 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-44.65± 2.715(-50.005 to -39.293) OG001-50.25± 2.755(-55.688 to -44.819) OG002-51.56± 2.757(56.999 to 46.123)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Literature-based estimates of WASO (Wake After Sleep Onset) SD (Standard Deviation) range from 39 to 45 minutes. Null hypothesis: difference between mean WASO3-7 values for placebo and the 15-mg SKP-1041 dose level equals 0. By using a 2-sided, 1-sample t test at the 5% level of significance of this null hypothesis and an assumed SD of 45 minutes, a sample size of 54 completed patients was calculated to provide 90% power to detect a mean treatment difference of 20 minutes.	Mixed Models Analysis	No adjustment for multiple testing was made for secondary efficacy endpoints.	0.1476	Adjusted mean differences were analyzed via general linear model that used change from baseline as response variable and included effects for patient, period, sequence, and treatment.	Mean Difference (Net)	-5.604	Standard Error of the Mean	2.755	2-Sided	95	-13.208	2.000

Secondary

Total Sleep Time 3-7 Hours Post-dose

Total Sleep Time during hours 3-7 (inclusive) post-dose

Intention to Treat population (all randomized patients)

Posted

Mean

Standard Error

Minutes

hours 3-7 (inclusive) post-dose

ID	Title	Description
OG000	Placebo (Sugar Pill)	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo in place of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two placebo tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG001	10 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 10mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 10 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG002	15 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 15mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 15 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG003	20 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 20mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two 10 mg SKP-1041 tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Units	Counts
Participants	OG00067 OG00167 OG00267 OG003

Title

Denominators

Categories

Title	Measurements
	OG00039.03± 2.365 OG00147.86± 2.400 OG00249.46± 2.401 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The adjusted mean differences were analyzed by using a general linear model that used change from baseline as the response variable and included effects for patient, period, sequence, and treatment.	Mixed Models Analysis		0.0092	All aspects of the study's primary endpoint were statistically significant, and no adjustment for multiple testing was made for secondary efficacy endpoints.	Mean Difference (Net)	8.831	Standard Error of the Mean	2.400	2-Sided	95	2.208	15.454			A positive mean difference from baseline indicates an improvement.	No

Secondary

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)

Intention to Treat dataset (all randomized patients)

Posted

Mean

Standard Error

Number of awakenings

hours 3-7 (inclusive) post-dose

ID	Title	Description
OG000	Placebo	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo in place of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two placebo tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG001	10 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 10mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 10 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG002	15 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 15mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 15 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG003	20 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 20mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two 10 mg SKP-1041 tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Units	Counts
Participants	OG00067 OG00167 OG00267 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.40± 0.240 OG001-1.96± 0.244 OG002-2.43± 0.244 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This endpoint summarizes the number of times during Hours 3 7, after onset of persistent sleep, that there was a wake entry of at least 2 epochs duration. To be counted, each entry must have been separated by a sleep stage of 2, 3 4, or rapid eye movement.	Mixed Models Analysis	No adjustment for multiple testing was made for secondary efficacy endpoints.	0.1005	Adjusted mean differences were analyzed with a general linear model that used change from baseline as the response variable and included effects for patient, period,sequence, and treatment.	Mean Difference (Net)	-0.562	Standard Error of the Mean	0.244	2-Sided	95	-1.235	0.110			A negative mean change from baseline indicates an improvement.

Secondary

Subjective Wake Time After Sleep Onset (sWASO)

Subjective wake time after sleep onset sourced from the Morning Sleep Questionnaire self-assessment

All Efficacy Analyses were performed on the Intention to Treat (ITT) population (all randomized patients).

Posted

Mean

Standard Error

minutes

9 hours after tablet ingestion

ID	Title	Description
OG000	Placebo	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo in place of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two placebo tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG001	10 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 10mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 10 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG002	15 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 15mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 15 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG003	20 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 20mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two 10 mg SKP-1041 tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Units	Counts
Participants	OG00067 OG00167 OG00267 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-14.05± 4.873 OG001-22.50± 4.869 OG002-12.68± 4.937 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Study was powered on the primary endpoint. Data for sWASO were sourced from Question 5 of the Morning Sleep Questionnaire. Its analysis follows a general linear model change from baseline as response variable including effects for patient, period, sequence, and treatment.	Mixed Models Analysis	No adjustment for multiple testing was made for secondary efficacy endpoints.	0.2190	Mean (SEM) = adjusted mean change from baseline in each group (and standard error of the mean) and P value = P value for the comparison of the SEM of the active group with that of the placebo group.	Mean Difference (Net)	-8.452	Standard Error of the Mean	0.2190	2-Sided	95	-21.980	5.077

Secondary

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.

Intention to Treat population (all randomized patients)

Posted

Mean

Standard Error

percentage change from mean baseline

9 hours after tablet ingestion

ID	Title	Description
OG000	Placebo	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo in place of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two placebo tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG001	10 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 10mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 10 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG002	15 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 15mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 15 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG003	20 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 20mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two 10 mg SKP-1041 tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Units	Counts
Participants	OG00067 OG00167 OG00267 OG003

Title

Denominators

Categories

Title	Measurements
	OG0008.56± 1.434 OG0019.26± 1.469 OG0026.59± 1.523 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Adjusted mean differences were analyzed by using a general linear model that used change from baseline as the response variable.	Mixed Models Analysis		0.6433	Analysis included effects for patient, period, sequence and treatment.	Mean Difference (Net)	0.560	Standard Error of the Mean	1.469	2-Sided	95	-1.823	2.943			A positive mean difference from baseline indicates improvement.	No	Superiority or Other

Secondary

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.

Intention to Treat population (all randomized patients)

Posted

Mean

Standard Error

units on a scale change from baseline

9 hours post-dose

ID	Title	Description
OG000	Placebo	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo in place of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two placebo tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG001	10 mg SKP=1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 10mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 10 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG002	15 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 15mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 15 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG003	20 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 20mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two 10 mg SKP-1041 tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Units	Counts
Participants	OG00067 OG00167 OG00267 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.23± 0.268 OG0010.71± 0.256 OG0020.40± 0.259 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The adjusted mean differences were analyzed with a general linear model that used change from baseline as the response variable and included effects for patient, period, sequence and treatment.	Mixed Models Analysis		0.0914		Mean Difference (Net)	0.450	Standard Error of the Mean	0.256	2-Sided	95	-0.073	0.972			A positive mean change from baseline indicates an improvement.	No	Superiority or Other

Secondary

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.

Safety population (patients exposed to that given treatment)

Posted

Mean

Standard Error

mm change from baseline

9 hours after tablet ingestion

ID	Title	Description
OG000	Placebo (Sugar Pill)	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive placebo in place of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two placebo tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG001	10 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 10 mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 10 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG002	15 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 15mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. One 15 mg SKP-1041 tablet and one placebo tablet were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.
OG003	20 mg SKP-1041	Each patient was assigned at some point in their randomized crossover sequence of four treatment arms to receive 20mg of the investigational zaleplon delayed and sustained release SKP-1041 tablets. Two 10 mg SKP-1041 tablets were administered orally at bedtime for each of two consecutive nights during the Sleep Study. Afterward, patients were released from the sleep laboratory, washed out at home for 4-7 days, and returned to the sleep lab for the next treatment in their randomized sequence.

Units	Counts
Participants	OG00066 OG00165 OG00265 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003.48± 2.195 OG0013.83± 1.818 OG0023.55± 2.422 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	The Model included effects for patient, period, sequence and treatment.	0.7190	Adjusted mean differences were analyzed in a general linear model that used change from baseline as the response variable.	Mean Difference (Net)	0.710	Standard Error of the Mean	1.818	2-Sided	95	-3.175	4.595			A positive mean change from baseline indicates improvement.	No	Superiority or Other

Secondary

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).

Pharmacokinetic Population--Patients who completed night 3 of Visit 6 (the PK substudy). Note that these patients had participated in a crossover design across all doses for the sleep study but had PK assessments only for one dose (parallel group design).

Posted

Mean

Standard Error

ng/mL

Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)

Blood samples

Participants

ID	Title	Description
OG000	10 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 10 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG001	15 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 15 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG002	20 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered two 10 mg SKP-1041 tablets at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.

Units	Counts
Participants	OG00017 OG00113 OG00215
Blood samples	OG000

Title

Denominators

Categories

Title	Measurements
	OG00017.9± 1.3 OG00125.3± 2.9 OG00234.4± 4.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	Cmax(ng/mL) [Maximum plasma zaleplon concentration]	ANOVA	F-test 2 degrees of freedom	0.0009		Mean Difference (Net)	8.39			2-Sided							No	Superiority or Other

Secondary

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).

Posted

Mean

Standard Error

ng/mL/mg zaleplon

Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)

Blood Samples

Participants

ID	Title	Description
OG000	10 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 10 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG001	15 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 15 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG002	20 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered two 10 mg SKP-1041 tablets at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.

Units	Counts
Participants	OG00017 OG00113 OG00215
Blood Samples	OG000

Title

Denominators

Categories

Title	Measurements
	OG0001.8± 0.1 OG0011.7± 0.2 OG0021.7± 0.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	Cmax normalized per dose	ANOVA	F-test two degrees of freedom	0.9142		Mean Difference (Net)	0.09				95						No	Superiority or Other

Secondary

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.

Posted

Mean

Standard Error

Hours post-dose

Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)

Blood Samples

Participants

ID	Title	Description
OG000	10 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 10 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG001	15 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 15 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG002	20 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered two 10 mg SKP-1041 tablets at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.

Units	Counts
Participants	OG00017 OG00113 OG00215
Blood Samples	OG000

Title

Denominators

Categories

Title	Measurements
	OG0004± 2.5 OG0014± 2.5 OG0024± 3.6

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	Time (hour)post-dose of maximum plasma zaleplon concentration	ANOVA	F-test 2 degrees of freedom	0.1193		Mean Difference (Net)	2.24				95						No	Superiority or Other

Secondary

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).

Posted

Mean

Standard Error

ng x h/mL

Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)

Blood Samples

Participants

ID	Title	Description
OG000	10 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 10 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG001	15 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 15 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG002	20 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered two 10 mg SKP-1041 tablets at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.

Units	Counts
Participants	OG00017 OG00113 OG00215
Blood Samples	OG000

Title

Denominators

Categories

Title	Measurements
	OG00056.5± 3.9 OG00177.4± 5.6 OG002135.3± 22.0

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	AUC ng*h/mL)	ANOVA	F-test 2 degrees of freedom	0.0003		Mean Difference (Net)	9.85				95						No	Superiority or Other

Secondary

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.

Posted

Mean

Standard Error

ng*h/mL/mg

Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)

Blood Samples

Participants

ID	Title	Description
OG000	10 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 10 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG001	15 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 15 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG002	20 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered two 10 mg SKP-1041 tablets at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.

Units	Counts
Participants	OG00017 OG00113 OG00215
Blood Samples	OG000

Title

Denominators

Categories

Title	Measurements
	OG0005.36± 0.4 OG0015.20± 0.4 OG0026.76± 1.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	AUC/Dose (ng*h/mL/mg)	ANOVA	F-test 2 degrees of freedom	0.2281		Mean Difference (Net)	1.28				95						No	Superiority or Other

Secondary

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).

Posted

Mean

Standard Error

hour

Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7)

Blood Samples

Participants

ID	Title	Description
OG000	10 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 10 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG001	15 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered one placebo and one 15 mg SKP-1041 tablet at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.
OG002	20 mg SKP-1041	The fourth and final treatment period included a third night at the site during which all patients continued to receive the same study medication as on the first 2 nights of this treatment period. Patients randomized to this group were administered two 10 mg SKP-1041 tablets at bedtime for the third time. Blood was drawn from all patients for PK analyses at specific time intervals.

Units	Counts
Participants	OG00017 OG00113 OG00215
Blood Samples	OG000

Title

Denominators

Categories

Title	Measurements
	OG0001.52± 0.05 OG0011.65± 0.17 OG0021.47± 0.09

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	Half-Life (t1/2 in hours) of plasma zaleplon from each of 3 doses of SKP-1041	ANOVA	2 degrees of freedom F-test	0.4835		Mean Difference (Net)	0.74				95						No	Superiority or Other