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 Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of MK0249 in treating refractory excessive daytime sleepiness (EDS) in patients with Obstructive Sleep Apnea/Hypopnea Syndrome (OSA/HS) using nasal continuous positive airway pressure (nCPAP) therapy.

Official Title
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Phase IIa, Randomized, Double-blind, Placebo-controlled, 3-period Crossover, Adaptive Dose Design, Clinical Trial to Evaluate Safety & Efficacy of MK0249 in Treating Refractory Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea/Hypopnea Syndrome Appropriately Using nCPAP Therapy.

Conditions
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Sleep Apnea, Obstructive, Hypopnea Syndrome, Excessive Daytime Sleepiness

Intervention / Treatment
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* Drug: Comparator: MK0249
* Drug: Comparator: placebo
* Drug: Comparator: modafinil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is male or female and is at least 18 years old and less than 65 years old Patient must have a diagnosis of Obstructive Sleep Apnea/Hypopnea Syndrome Patient has been using nCPAP treatment for at least 2 months prior to Visit 1 Patient is willing to stay at a sleep laboratory for 4 full days and nights for observation and assessments Patient is willing to refrain from napping for the duration of the study Exclusion Criteria: Patient is pregnant, breastfeeding, or planning to become pregnant within the next 4 months Patient is or has participated in a study with an investigational compound or device within 30 days of signing the informed consent Patient has had asthma-related visit to the emergency room or hospitalization within 6 months of Visit 1 Patient has donated or received blood products within 8 weeks of signing consent or is planning on doing either for the 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: 1<br>Arm 1: Treatment period 1: MK0249; Treatment period 2: Placebo; Treatment period 3: modafinil | Drug: Comparator: MK0249<br>* Patients will be assigned to receive MK0249 film coated tablet (FCT). The doses of MK0249 that are included for possible investigation (depending upon an adaptive allocation process) are 3 mg, 5 mg, 8 mg, 10 mg, and 12 mg. Study medication will be taken for 14 days, during each of the 3 treatment periods, by mouth (po) once a day (qd).<br>Drug: Comparator: placebo<br>* Placebo; Patients will be assigned to receive placebo, across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>Drug: Comparator: modafinil<br>* Patients will be assigned to receive modafinil 200mg oral compressed tablet (OCT), across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>|
| Experimental: 2<br>Arm 2: Treatment period 1: Placebo; Treatment period 2: modafinil; Treatment period 3: MK0249 | Drug: Comparator: MK0249<br>* Patients will be assigned to receive MK0249 film coated tablet (FCT). The doses of MK0249 that are included for possible investigation (depending upon an adaptive allocation process) are 3 mg, 5 mg, 8 mg, 10 mg, and 12 mg. Study medication will be taken for 14 days, during each of the 3 treatment periods, by mouth (po) once a day (qd).<br>Drug: Comparator: placebo<br>* Placebo; Patients will be assigned to receive placebo, across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>Drug: Comparator: modafinil<br>* Patients will be assigned to receive modafinil 200mg oral compressed tablet (OCT), across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>|
| Experimental: 3<br>Arm 3: Treatment period 1: modafinil; Treatment period 2: MK0249; Treatment period 3: Placebo | Drug: Comparator: MK0249<br>* Patients will be assigned to receive MK0249 film coated tablet (FCT). The doses of MK0249 that are included for possible investigation (depending upon an adaptive allocation process) are 3 mg, 5 mg, 8 mg, 10 mg, and 12 mg. Study medication will be taken for 14 days, during each of the 3 treatment periods, by mouth (po) once a day (qd).<br>Drug: Comparator: placebo<br>* Placebo; Patients will be assigned to receive placebo, across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>Drug: Comparator: modafinil<br>* Patients will be assigned to receive modafinil 200mg oral compressed tablet (OCT), across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>|
| Experimental: 4<br>Arm 4: Treatment period 1: MK0249; Treatment period 2: modafinil; Treatment period 3: Placebo | Drug: Comparator: MK0249<br>* Patients will be assigned to receive MK0249 film coated tablet (FCT). The doses of MK0249 that are included for possible investigation (depending upon an adaptive allocation process) are 3 mg, 5 mg, 8 mg, 10 mg, and 12 mg. Study medication will be taken for 14 days, during each of the 3 treatment periods, by mouth (po) once a day (qd).<br>Drug: Comparator: placebo<br>* Placebo; Patients will be assigned to receive placebo, across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>Drug: Comparator: modafinil<br>* Patients will be assigned to receive modafinil 200mg oral compressed tablet (OCT), across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>|
| Experimental: 5<br>Arm 5: Treatment period 1: Placebo; Treatment period 2: MK0249; Treatment period 3: modafinil | Drug: Comparator: MK0249<br>* Patients will be assigned to receive MK0249 film coated tablet (FCT). The doses of MK0249 that are included for possible investigation (depending upon an adaptive allocation process) are 3 mg, 5 mg, 8 mg, 10 mg, and 12 mg. Study medication will be taken for 14 days, during each of the 3 treatment periods, by mouth (po) once a day (qd).<br>Drug: Comparator: placebo<br>* Placebo; Patients will be assigned to receive placebo, across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>Drug: Comparator: modafinil<br>* Patients will be assigned to receive modafinil 200mg oral compressed tablet (OCT), across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>|
| Experimental: 6<br>Arm 6: Treatment period 1: modafinil; Treatment period 2: Placebo; Treatment period 3: MK0249 | Drug: Comparator: MK0249<br>* Patients will be assigned to receive MK0249 film coated tablet (FCT). The doses of MK0249 that are included for possible investigation (depending upon an adaptive allocation process) are 3 mg, 5 mg, 8 mg, 10 mg, and 12 mg. Study medication will be taken for 14 days, during each of the 3 treatment periods, by mouth (po) once a day (qd).<br>Drug: Comparator: placebo<br>* Placebo; Patients will be assigned to receive placebo, across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>Drug: Comparator: modafinil<br>* Patients will be assigned to receive modafinil 200mg oral compressed tablet (OCT), across 3 treatment periods. Study medication will be taken for 14 days, during each of the 3 treatment periods, po qd.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of Average Maintenance of Wakefulness Test Early for The Mode Dose of MK0249 Versus Placebo | The Maintenance of Wakefulness Test (MWT) is an objective assessment of sleepiness that measures the ability of a patient to remain awake. The primary endpoint was the mean of sleep latency (average of the first 4 MWTs which were at 0900, 1100, 1300, and 1500), where latency for each MWT was defined as the time to onset of the first 16 continuous seconds of any stage of sleep; if no sleep was observed according to these rules, then latency was defined as 30 minutes. The comparison was for the mode dose of MK0249 versus placebo. | At Week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of Average Maintenance of Wakefulness Test Early for the Mode Dose of MK0249 Versus Modafinil | The Maintenance of Wakefulness Test (MWT) is an objective assessment of sleepiness that measures the ability of a patient to remain awake. The primary endpoint was the mean of sleep latency (average of the first 4 MWTs which were at 0900, 1100, 1300, and 1500), where latency for each MWT was defined as the time to onset of the first 16 continuous seconds of any stage of sleep; if no sleep was observed according to these rules, then latency was defined as 30 minutes. The comparison was for the mode dose of MK0249 versus modafinil. | At Week 2 | 
| Mean of Average Maintenance of Wakefulness Test Early for Top 2 Doses Pooled of MK0249 Versus Modafinil | The Maintenance of Wakefulness Test (MWT) is an objective assessment of sleepiness that measures the ability of a patient to remain awake. The primary endpoint was the mean of sleep latency (average of the first 4 MWTs which were at 0900, 1100, 1300, and 1500), where latency for each MWT was defined as the time to onset of the first 16 continuous seconds of any stage of sleep; if no sleep was observed according to these rules, then latency was defined as 30 minutes. The comparison was for the top 2 doses pooled of MK0249 versus modafinil. | At Week 2 | 
| Clinical Global Impressions Scale of Severity Score as it Relates to Excessive Daytime Sleepiness (CGIS-EDS) for the Mode Dose of MK0249 Versus Placebo | Clinical Global Impressions Scale of Severity (CGI-S) is a subscale of the CGI which is a standard psychometric scale used to demonstrate changes and improvements in illness. CGI-S consists of a 7-point scale rated from 1 to 7. The investigator or sponsor-approved clinician judged how ill the patient was with respect to Excessive Daytime Sleepiness (EDS) at the time of the CGI-S rating (CGIS-EDS), with higher scores indicating more severe illness. | At Week 2 | 
| Epworth Sleepiness Scale (ESS) Score for the Mode Dose of MK0249 Versus Placebo | The Epworth Sleepiness Scale (ESS) is a self-administered questionnaire that provides subjective reports that equate with sleep propensity, not with 'subjective sleepiness'. Having a high sleep propensity means having a history of dozing in situations that have a relatively low soporific nature, in which normal subjects seldom doze. The ESS consists of eight items, which are rated from 0 (would never dose) to 3 (high chance of dozing). The ESS score is the total score of the 8 individual items; this total score ranges from 0 to 24 (higher total score is worse). | At Week 2 |