Treatment of Refractory Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea/Hypopnea Syndrome (OSA/HS) Using Nasal Continuous Positive Airway Pressure (nCPAP) Therapy (0249-015) - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Conditions:	Sleep Apnea, Obstructive Hypopnea Syndrome Excessive Daytime Sleepiness
Interventions:	Drug: Comparator: MK0249 Drug: Comparator: placebo Drug: Comparator: modafinil

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The majority of patients were recruited from investigators' own databases at 24 sites in the United States. The primary therapy period was 13-Mar-2008 to 25-Feb-2009.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants maintained sleep and sleepiness diaries during a 7- to 10-day placebo run-in period. They used a nasal continuous positive airway pressure (nCPAP) device to monitor their CPAP use. At the end of the run-in period, participants stayed overnight at the clinic for nighttime polysomnography and if eligible, were randomized the next morning

Reporting Groups

	Description
MK0249/Placebo/Modafinil	Eligible participants were equally randomized to 1 of 6 treatment sequences: MK0249/Placebo/Modafinil, Placebo/Modafinil/MK0249, Modafinil/MK0249/Placebo, MK0249/Modafinil/Placebo, Placebo/MK0249/Modafinil, Modafinil/Placebo/MK0249. The dose of the MK0249 was determined according to a predefined adaptive algorithm. Treatment period was determined by the sequence to which the participant was randomized. Each treatment period was followed by a 7-day placebo washout period. MK0249 was provided as 1 mg and 5 mg tablets. Modafinil was provided as 100 mg tablets. Matching placebo tablets were provided for the MK0249 1 and 5 mg tablets and for the modafinil 100 mg tablet.
Placebo/Modafinil/MK0249	Eligible participants were equally randomized to 1 of 6 treatment sequences: MK0249/Placebo/Modafinil, Placebo/Modafinil/MK0249, Modafinil/MK0249/Placebo, MK0249/Modafinil/Placebo, Placebo/MK0249/Modafinil, Modafinil/Placebo/MK0249. The dose of the MK0249 was determined according to a predefined adaptive algorithm. Treatment period was determined by the sequence to which the participant was randomized. Each treatment period was followed by a 7-day placebo washout period. MK0249 was provided as 1 mg and 5 mg tablets. Modafinil was provided as 100 mg tablets. Matching placebo tablets were provided for the MK0249 1 and 5 mg tablets and for the modafinil 100 mg tablet.
Modafinil/MK0249/Placebo	Eligible participants were equally randomized to 1 of 6 treatment sequences: MK0249/Placebo/Modafinil, Placebo/Modafinil/MK0249, Modafinil/MK0249/Placebo, MK0249/Modafinil/Placebo, Placebo/MK0249/Modafinil, Modafinil/Placebo/MK0249. The dose of the MK0249 was determined according to a predefined adaptive algorithm. Treatment period was determined by the sequence to which the participant was randomized. Each treatment period was followed by a 7-day placebo washout period. MK0249 was provided as 1 mg and 5 mg tablets. Modafinil was provided as 100 mg tablets. Matching placebo tablets were provided for the MK0249 1 and 5 mg tablets and for the modafinil 100 mg tablet.
MK0249/Modafinil/Placebo	Eligible participants were equally randomized to 1 of 6 treatment sequences: MK0249/Placebo/Modafinil, Placebo/Modafinil/MK0249, Modafinil/MK0249/Placebo, MK0249/Modafinil/Placebo, Placebo/MK0249/Modafinil, Modafinil/Placebo/MK0249. The dose of the MK0249 was determined according to a predefined adaptive algorithm. Treatment period was determined by the sequence to which the participant was randomized. Each treatment period was followed by a 7-day placebo washout period. MK0249 was provided as 1 mg and 5 mg tablets. Modafinil was provided as 100 mg tablets. Matching placebo tablets were provided for the MK0249 1 and 5 mg tablets and for the modafinil 100 mg tablet.
Placebo/MK0249/Modafinil	Eligible participants were equally randomized to 1 of 6 treatment sequences: MK0249/Placebo/Modafinil, Placebo/Modafinil/MK0249, Modafinil/MK0249/Placebo, MK0249/Modafinil/Placebo, Placebo/MK0249/Modafinil, Modafinil/Placebo/MK0249. The dose of the MK0249 was determined according to a predefined adaptive algorithm. Treatment period was determined by the sequence to which the participant was randomized. Each treatment period was followed by a 7-day placebo washout period. MK0249 was provided as 1 mg and 5 mg tablets. Modafinil was provided as 100 mg tablets. Matching placebo tablets were provided for the MK0249 1 and 5 mg tablets and for the modafinil 100 mg tablet.
Modafinil/Placebo/MK0249	Eligible participants were equally randomized to 1 of 6 treatment sequences: MK0249/Placebo/Modafinil, Placebo/Modafinil/MK0249, Modafinil/MK0249/Placebo, MK0249/Modafinil/Placebo, Placebo/MK0249/Modafinil, Modafinil/Placebo/MK0249. The dose of the MK0249 was determined according to a predefined adaptive algorithm. Treatment period was determined by the sequence to which the participant was randomized. Each treatment period was followed by a 7-day placebo washout period. MK0249 was provided as 1 mg and 5 mg tablets. Modafinil was provided as 100 mg tablets. Matching placebo tablets were provided for the MK0249 1 and 5 mg tablets and for the modafinil 100 mg tablet.

Participant Flow for 5 periods

Period 1: Treatment Period 1

	MK0249/Placebo/Modafinil	Placebo/Modafinil/MK0249	Modafinil/MK0249/Placebo	MK0249/Modafinil/Placebo	Placebo/MK0249/Modafinil	Modafinil/Placebo/MK0249
STARTED	21	21	21	21	21	20
COMPLETED	18	21	20	18 ^[1]	20	20
NOT COMPLETED	3	0	1	3	1	0
Adverse Event	1	0	0	3	0	0
Protocol Violation	1	0	0	0	0	0
Withdrawal by Subject	1	0	1	0	1	0

[1]	1 patient discontinued from MK0249, but continued in following periods, & completed the study

Period 2: Placebo Washout Period 1

	MK0249/Placebo/Modafinil	Placebo/Modafinil/MK0249	Modafinil/MK0249/Placebo	MK0249/Modafinil/Placebo	Placebo/MK0249/Modafinil	Modafinil/Placebo/MK0249
STARTED	18	21	20	19	20	20
COMPLETED	18	21	20	18	20	20
NOT COMPLETED	0	0	0	1	0	0
Withdrawal by Subject	0	0	0	1	0	0

Period 3: Treatment Period 2

	MK0249/Placebo/Modafinil	Placebo/Modafinil/MK0249	Modafinil/MK0249/Placebo	MK0249/Modafinil/Placebo	Placebo/MK0249/Modafinil	Modafinil/Placebo/MK0249
STARTED	18	21	20	18	20	20
COMPLETED	18	18	19	18	15	20
NOT COMPLETED	0	3	1	0	5	0
Adverse Event	0	3	0	0	2	0
Withdrawal by Subject	0	0	1	0	3	0

Period 4: Placebo Washout Period 2

	MK0249/Placebo/Modafinil	Placebo/Modafinil/MK0249	Modafinil/MK0249/Placebo	MK0249/Modafinil/Placebo	Placebo/MK0249/Modafinil	Modafinil/Placebo/MK0249
STARTED	18	18	19	18	15	20
COMPLETED	16	18	19	18	15	20
NOT COMPLETED	2	0	0	0	0	0
Adverse Event	2	0	0	0	0	0

Period 5: Treatment Period 3

	MK0249/Placebo/Modafinil	Placebo/Modafinil/MK0249	Modafinil/MK0249/Placebo	MK0249/Modafinil/Placebo	Placebo/MK0249/Modafinil	Modafinil/Placebo/MK0249
STARTED	16	18	19	18	15	20
COMPLETED	16	16	19	17	15	20
NOT COMPLETED	0	2	0	1	0	0
Adverse Event	0	2	0	0	0	0
Withdrawal by Subject	0	0	0	1	0	0

Baseline Characteristics

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Reporting Groups

	Description
All Randomized Participants	All participants randomized in study

Baseline Measures

	All Randomized Participants
Number of Participants [units: participants]	125
Age [units: years] Mean ± Standard Deviation	48.6 ± 8.5
Gender [units: participants]
Female	25
Male	100
Race/Ethnicity, Customized [units: participants]
White	102
Black or African American	19
American Indian or Alaska Native	1
Asian	3

Outcome Measures

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1. Primary:

Mean of Average Maintenance of Wakefulness Test Early for The Mode Dose of MK0249 Versus Placebo [ Time Frame: At Week 2 ]

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2. Secondary:

Mean of Average Maintenance of Wakefulness Test Early for the Mode Dose of MK0249 Versus Modafinil [ Time Frame: At Week 2 ]

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3. Secondary:

Mean of Average Maintenance of Wakefulness Test Early for Top 2 Doses Pooled of MK0249 Versus Modafinil [ Time Frame: At Week 2 ]

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4. Secondary:

Clinical Global Impressions Scale of Severity Score as it Relates to Excessive Daytime Sleepiness (CGIS-EDS) for the Mode Dose of MK0249 Versus Placebo [ Time Frame: At Week 2 ]

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5. Secondary:

Epworth Sleepiness Scale (ESS) Score for the Mode Dose of MK0249 Versus Placebo [ Time Frame: At Week 2 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Vice President of Late Stage Development
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@spcorp.com

No publications provided

Responsible Party:	Vice President of Late Stage Development, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00620659 History of Changes
Other Study ID Numbers:	MK-0249-015, 2007_602
Study First Received:	January 10, 2008
Results First Received:	October 13, 2010
Last Updated:	January 27, 2011
Health Authority:	United States: Food and Drug Administration