search
Back to results

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)

Primary Purpose

Sleep Apnea, Obstructive, Hypopnea Syndrome, Excessive Daytime Sleepiness

Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Comparator: MK0249
Comparator: placebo
Comparator: modafinil
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Apnea, Obstructive

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    1

    2

    3

    4

    5

    6

    Arm Description

    Arm 1: Treatment period 1: MK0249; Treatment period 2: Placebo; Treatment period 3: modafinil

    Arm 2: Treatment period 1: Placebo; Treatment period 2: modafinil; Treatment period 3: MK0249

    Arm 3: Treatment period 1: modafinil; Treatment period 2: MK0249; Treatment period 3: Placebo

    Arm 4: Treatment period 1: MK0249; Treatment period 2: modafinil; Treatment period 3: Placebo

    Arm 5: Treatment period 1: Placebo; Treatment period 2: MK0249; Treatment period 3: modafinil

    Arm 6: Treatment period 1: modafinil; Treatment period 2: Placebo; Treatment period 3: MK0249

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    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.
    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).

    Full Information

    First Posted
    January 10, 2008
    Last Updated
    April 27, 2015
    Sponsor
    Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00620659
    Brief Title
    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)
    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.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2015
    Overall Recruitment Status
    Terminated
    Study Start Date
    February 2008 (undefined)
    Primary Completion Date
    February 2009 (Actual)
    Study Completion Date
    February 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Sleep Apnea, Obstructive, Hypopnea Syndrome, Excessive Daytime Sleepiness

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    125 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    1
    Arm Type
    Experimental
    Arm Description
    Arm 1: Treatment period 1: MK0249; Treatment period 2: Placebo; Treatment period 3: modafinil
    Arm Title
    2
    Arm Type
    Experimental
    Arm Description
    Arm 2: Treatment period 1: Placebo; Treatment period 2: modafinil; Treatment period 3: MK0249
    Arm Title
    3
    Arm Type
    Experimental
    Arm Description
    Arm 3: Treatment period 1: modafinil; Treatment period 2: MK0249; Treatment period 3: Placebo
    Arm Title
    4
    Arm Type
    Experimental
    Arm Description
    Arm 4: Treatment period 1: MK0249; Treatment period 2: modafinil; Treatment period 3: Placebo
    Arm Title
    5
    Arm Type
    Experimental
    Arm Description
    Arm 5: Treatment period 1: Placebo; Treatment period 2: MK0249; Treatment period 3: modafinil
    Arm Title
    6
    Arm Type
    Experimental
    Arm Description
    Arm 6: Treatment period 1: modafinil; Treatment period 2: Placebo; Treatment period 3: MK0249
    Intervention Type
    Drug
    Intervention Name(s)
    Comparator: MK0249
    Intervention Description
    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).
    Intervention Type
    Drug
    Intervention Name(s)
    Comparator: placebo
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Comparator: modafinil
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Mean of Average Maintenance of Wakefulness Test Early for The Mode Dose of MK0249 Versus Placebo
    Description
    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.
    Time Frame
    At Week 2
    Secondary Outcome Measure Information:
    Title
    Mean of Average Maintenance of Wakefulness Test Early for the Mode Dose of MK0249 Versus Modafinil
    Description
    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.
    Time Frame
    At Week 2
    Title
    Mean of Average Maintenance of Wakefulness Test Early for Top 2 Doses Pooled of MK0249 Versus Modafinil
    Description
    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.
    Time Frame
    At Week 2
    Title
    Clinical Global Impressions Scale of Severity Score as it Relates to Excessive Daytime Sleepiness (CGIS-EDS) for the Mode Dose of MK0249 Versus Placebo
    Description
    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.
    Time Frame
    At Week 2
    Title
    Epworth Sleepiness Scale (ESS) Score for the Mode Dose of MK0249 Versus Placebo
    Description
    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).
    Time Frame
    At Week 2

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    64 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    23920422
    Citation
    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.
    Results Reference
    result

    Learn more about this trial

    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)

    We'll reach out to this number within 24 hrs