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) - Full Text View

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00620659

Purpose

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.

Condition	Intervention	Phase
Sleep Apnea, Obstructive Hypopnea Syndrome Excessive Daytime Sleepiness	Drug: Comparator: MK0249 Drug: Comparator: placebo Drug: Comparator: modafinil	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	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.

Resource links provided by NLM:

MedlinePlus related topics: Sleep Apnea

Drug Information available for: Modafinil

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Mean of Average Maintenance of Wakefulness Test Early for The Mode Dose of MK0249 Versus Placebo [ Time Frame: At Week 2 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Mean of Average Maintenance of Wakefulness Test Early for the Mode Dose of MK0249 Versus Modafinil [ Time Frame: At Week 2 ] [ Designated as safety issue: No ]
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.
Mean of Average Maintenance of Wakefulness Test Early for Top 2 Doses Pooled of MK0249 Versus Modafinil [ Time Frame: At Week 2 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
Epworth Sleepiness Scale (ESS) Score for the Mode Dose of MK0249 Versus Placebo [ Time Frame: At Week 2 ] [ Designated as safety issue: No ]
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).

Enrollment:	125
Study Start Date:	February 2008
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility

Ages Eligible for Study:	18 Years to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620659

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

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

Additional relevant MeSH terms:

Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders

Nervous System Diseases
Modafinil
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on February 09, 2012