Pharmacodynamics and Efficacy of MK-7288 in Adults With Sleep Apnea (MK-7288-010)

Study Overview
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Brief Summary
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This is a study of the safety and efficacy of MK-7288 for the treatment of excessive daytime sleepiness (EDS) in participants with obstructive sleep apnea (OSA)/hypopnea syndrome (HS) who are compliant with effective nasal continuous positive airway pressure (nCPAP) therapy. The goal of this study is to determine the effect of MK-7288 after single dose administration on promoting wakefulness as measured by sleep latency on Maintenance of Wakefulness Tests, and on driving performance as measured by standard deviation of lane position in simulated driving (country vigilance driving).

Official Title
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An Active-Comparator Controlled Single Dose Study to Evaluate the Pharmacodynamics/Efficacy of MK-7288 in Sleep Apnea Patients

Conditions
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Apnea, Sleep

Intervention / Treatment
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* Drug: MK-7288
* Drug: Placebo to MK-7288
* Drug: Modafinil
* Drug: Placebo to modafinil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants are of non-child-bearing potential. Male participants who have female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study. Participant has an International Classification of Sleep Disorders diagnosis of Obstructive Sleep Apnea/Hypopnea Syndrome. Participant has excessive daytime sleepiness. Participant has been using nCPAP treatment for at least 2 months. Participant reported total sleep time of >6 hours on at least 4 out of 7 nights each week Participant is willing to stay at the sleep laboratory for 5 overnight stays. Participant is willing to limit caffeine and alcohol consumption during the study. Participant has a valid driver's license in the past 5 years and has had at least 1 year of driving experience within the past 3 years. Participant's regular bedtime is between 9:00 p.m. and 12:00 a.m. Exclusion Criteria: Participant has a history of cancer. Participant has any history of a significant neurological disorder. Participant has moderate or severe persistent asthma. Participant has a history of any of the following sleep disorders: narcolepsy, primary insomnia, Circadian rhythm sleep disorder, shift work sleep disorder, parasomnia including nightmare disorder, sleep terror disorder, rapid eye movement (REM) behavioral disorder, and sleepwalking disorder, periodic limb movement disorder, or restless leg syndrome. Participant consumes more than 10 cigarettes a day or routinely smokes during the night. Participant, in the opinion of the investigator, has a history or current evidence of any condition, therapy, lab abnormality or circumstances that might confound the results of the study, or interfere with participation for the full duration of the study.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-7288 10mg/Pbo/MK-7288 20mg/Modafinil<br>Participants received single doses of study drug in the following order: MK-7288 10 mg in Treatment Period 1, Placebo (Pbo) in Treatment Period 2, MK-7288 20 mg in Treatment Period 3 and Modafinil 200 mg in Treatment Period 4. The first 3 treatment periods were followed by a 7-day washout period. | Drug: MK-7288<br>* one or two 10 mg capsules, orally, single dose<br>Drug: Placebo to MK-7288<br>* one or two capsules, orally, single dose<br>Drug: Modafinil<br>* two 100 mg tablets, orally, single dose<br>* Other names: PROVIGIL®;Drug: Placebo to modafinil<br>* two 100 mg tablets, orally, single dose<br>|
| Experimental: MK-7288 20mg/MK-7288 10mg/Modafinil/Pbo<br>Participants received single doses of study drug in the following order: MK-7288 20 mg in Treatment Period 1, MK-7288 10 mg in Treatment Period 2, Modafinil 200 mg in Treatment Period 3 and Placebo in Treatment Period 4. The first 3 treatment periods were followed by a 7-day washout period. | Drug: MK-7288<br>* one or two 10 mg capsules, orally, single dose<br>Drug: Placebo to MK-7288<br>* one or two capsules, orally, single dose<br>Drug: Modafinil<br>* two 100 mg tablets, orally, single dose<br>* Other names: PROVIGIL®;Drug: Placebo to modafinil<br>* two 100 mg tablets, orally, single dose<br>|
| Experimental: Modafinil/MK-7288 20mg/Pbo/MK-7288 10mg<br>Participants received single doses of study drug in the following order: Modafinil 200 mg in Treatment Period 1, MK-7288 20 mg in Treatment Period 2, Placebo in Treatment Period 3 and MK-7288 10 mg in Treatment Period 4. The first 3 treatment periods were followed by a 7-day washout period. | Drug: MK-7288<br>* one or two 10 mg capsules, orally, single dose<br>Drug: Placebo to MK-7288<br>* one or two capsules, orally, single dose<br>Drug: Modafinil<br>* two 100 mg tablets, orally, single dose<br>* Other names: PROVIGIL®;Drug: Placebo to modafinil<br>* two 100 mg tablets, orally, single dose<br>|
| Experimental: Pbo/Modafinil/MK-7288 10 mg/MK-7288 20mg<br>Participants received single doses of study drug in the following order: Placebo in Treatment Period 1, Modafinil 200 mg in Treatment Period 2, MK-7288 10 mg in Treatment Period 3 and MK-7288 20 mg in Treatment Period 4. The first 3 treatment periods were followed by a 7-day washout period. | Drug: MK-7288<br>* one or two 10 mg capsules, orally, single dose<br>Drug: Placebo to MK-7288<br>* one or two capsules, orally, single dose<br>Drug: Modafinil<br>* two 100 mg tablets, orally, single dose<br>* Other names: PROVIGIL®;Drug: Placebo to modafinil<br>* two 100 mg tablets, orally, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sleep Latency Score on the Maintenance of Wakefulness Test (MWT) for Participants Taking MK-7288 Versus Placebo | Study drug was administered at 08:00. MWT, an objective measure of the participant's ability to maintain wakefulness, was administered at 09:00, 11:00, 13:00 and 15:00. A least squares (LS) mean of the 4 MWTs performed at 09:00, 11:00, 13:00 and 15:00 was calculated. Latency for each MWT is defined as the time to onset of the first 16 continuous seconds of any stage of sleep; if no sleep has been observed according to these rules, then the latency is defined as 30 minutes. A higher MWT value is considered a better outcome. | 1, 3, 5 and 7 hours post dose | 
| Mean Score on Standard Deviation of Lane Position (SDLP) Driving Test for Participants Taking MK-7288 Versus Placebo | Study drug was administered at 08:00. Driving performance was measured by the SDLP test which is a 45-minute driving simulation country vigilance test and was performed by participants at 10:00, 12:00 and 14:00. An LS mean of the 2 SDLP driving test results performed at 10:00 and 14:00 was calculated. A lower value is considered a better outcome. | 2, 4 and 6 hours post dose | 
| Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the study drug, is also an AE. | Up to 36 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sleep Latency Score on the MWT for Participants Taking MK-7288 Versus Modafinil | Study drug was administered at 08:00. MWT, an objective measure of the participant's ability to maintain wakefulness, was administered at 09:00, 11:00, 13:00 and 15:00. A least squares (LS) mean of the 4 MWTs performed at 09:00, 11:00, 13:00 and 15:00 was calculated. Latency for each MWT is defined as the time to onset of the first 16 continuous seconds of any stage of sleep; if no sleep has been observed according to these rules, then the latency is defined as 30 minutes. A higher MWT value is considered a better outcome. | 1, 3, 5 and 7 hours post dose | 
| Mean Sleep Latency Score on the MWT for Participants Taking Modafinil Versus Placebo | Study drug was administered at 08:00. MWT, an objective measure of the participant's ability to maintain wakefulness, was administered at 09:00, 11:00, 13:00 and 15:00. A least squares (LS) mean of the 4 MWTs performed at 09:00, 11:00, 13:00 and 15:00 was calculated. Latency for each MWT is defined as the time to onset of the first 16 continuous seconds of any stage of sleep; if no sleep has been observed according to these rules, then the latency is defined as 30 minutes. A higher MWT value is considered a better outcome. | 1, 3, 5 and 7 hours post dose | 
| Mean Score on SDLP Driving Test for Participants Taking Modafinil Versus Placebo | Study drug was administered at 08:00. Driving performance was measured by the SDLP test which is a 45-minute driving simulation country vigilance test and was performed by participants at 10:00, 12:00 and 14:00. An LS mean of the 2 SDLP driving test results performed at 10:00 and 14:00 was calculated. A lower value is considered a better outcome. | 2, 4 and 6 hours post dose |