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)

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.

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.

Study Overview

• Status: Terminated
• Conditions: Sleep Apnea, Obstructive; Hypopnea Syndrome; Excessive Daytime Sleepiness
• Intervention / Treatment: Drug: Comparator: MK0249; Drug: Comparator: placebo; Drug: Comparator: modafinil

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Arm 1: Treatment period 1: MK0249; Treatment period 2: Placebo; Treatment period 3: modafinil	Drug: Comparator: MK0249; 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).; Drug: Comparator: placebo; 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.; Drug: Comparator: modafinil; 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.
Experimental: 2; Arm 2: Treatment period 1: Placebo; Treatment period 2: modafinil; Treatment period 3: MK0249	Drug: Comparator: MK0249; 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).; Drug: Comparator: placebo; 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.; Drug: Comparator: modafinil; 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.
Experimental: 3; Arm 3: Treatment period 1: modafinil; Treatment period 2: MK0249; Treatment period 3: Placebo	Drug: Comparator: MK0249; 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).; Drug: Comparator: placebo; 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.; Drug: Comparator: modafinil; 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.
Experimental: 4; Arm 4: Treatment period 1: MK0249; Treatment period 2: modafinil; Treatment period 3: Placebo	Drug: Comparator: MK0249; 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).; Drug: Comparator: placebo; 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.; Drug: Comparator: modafinil; 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.
Experimental: 5; Arm 5: Treatment period 1: Placebo; Treatment period 2: MK0249; Treatment period 3: modafinil	Drug: Comparator: MK0249; 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).; Drug: Comparator: placebo; 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.; Drug: Comparator: modafinil; 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.
Experimental: 6; Arm 6: Treatment period 1: modafinil; Treatment period 2: Placebo; Treatment period 3: MK0249	Drug: Comparator: MK0249; 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).; Drug: Comparator: placebo; 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.; Drug: Comparator: modafinil; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Herring WJ, Liu K, Hutzelmann J, Snavely D, Snyder E, Ceesay P, Lines C, Michelson D, Roth T. Alertness and psychomotor performance effects of the histamine-3 inverse agonist MK-0249 in obstructive sleep apnea patients on continuous positive airway pressure therapy with excessive daytime sleepiness: a randomized adaptive crossover study. Sleep Med. 2013 Oct;14(10):955-63. doi: 10.1016/j.sleep.2013.04.010. Epub 2013 Aug 3.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: January 10, 2008
• First Submitted That Met QC Criteria: February 11, 2008
• First Posted (Estimate): February 21, 2008

Study Record Updates

• Last Update Posted (Estimate): May 13, 2015
• Last Update Submitted That Met QC Criteria: April 27, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disease; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Syndrome; Apnea; Disorders of Excessive Somnolence; Sleepiness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: 0249-015; 2007_602