Back to resultsPharmacodynamics and Efficacy of MK-7288 in Adults With Sleep Apnea (MK-7288-010)
Primary Purpose
Apnea, Sleep
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-7288
Placebo to MK-7288
Modafinil
Placebo to modafinil
Sponsored by
About this trial
This is an interventional treatment trial for Apnea, Sleep
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
MK-7288 10mg/Pbo/MK-7288 20mg/Modafinil
MK-7288 20mg/MK-7288 10mg/Modafinil/Pbo
Modafinil/MK-7288 20mg/Pbo/MK-7288 10mg
Pbo/Modafinil/MK-7288 10 mg/MK-7288 20mg
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
NCT ID
NCT01092780
First Posted
March 23, 2010
Last Updated
October 8, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01092780
Brief Title
Pharmacodynamics and Efficacy of MK-7288 in Adults With Sleep Apnea (MK-7288-010)
Official Title
An Active-Comparator Controlled Single Dose Study to Evaluate the Pharmacodynamics/Efficacy of MK-7288 in Sleep Apnea Patients
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
May 26, 2010 (Actual)
Primary Completion Date
May 31, 2011 (Actual)
Study Completion Date
May 31, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Apnea, Sleep
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK-7288 10mg/Pbo/MK-7288 20mg/Modafinil
Arm Type
Experimental
Arm Description
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.
Arm Title
MK-7288 20mg/MK-7288 10mg/Modafinil/Pbo
Arm Type
Experimental
Arm Description
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.
Arm Title
Modafinil/MK-7288 20mg/Pbo/MK-7288 10mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Pbo/Modafinil/MK-7288 10 mg/MK-7288 20mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MK-7288
Intervention Description
one or two 10 mg capsules, orally, single dose
Intervention Type
Drug
Intervention Name(s)
Placebo to MK-7288
Intervention Description
one or two capsules, orally, single dose
Intervention Type
Drug
Intervention Name(s)
Modafinil
Other Intervention Name(s)
PROVIGIL®
Intervention Description
two 100 mg tablets, orally, single dose
Intervention Type
Drug
Intervention Name(s)
Placebo to modafinil
Intervention Description
two 100 mg tablets, orally, single dose
Primary Outcome Measure Information:
Title
Mean Sleep Latency Score on the Maintenance of Wakefulness Test (MWT) for Participants Taking MK-7288 Versus Placebo
Description
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.
Time Frame
1, 3, 5 and 7 hours post dose
Title
Mean Score on Standard Deviation of Lane Position (SDLP) Driving Test for Participants Taking MK-7288 Versus Placebo
Description
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.
Time Frame
2, 4 and 6 hours post dose
Title
Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs)
Description
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.
Time Frame
Up to 36 days
Secondary Outcome Measure Information:
Title
Mean Sleep Latency Score on the MWT for Participants Taking MK-7288 Versus Modafinil
Description
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.
Time Frame
1, 3, 5 and 7 hours post dose
Title
Mean Sleep Latency Score on the MWT for Participants Taking Modafinil Versus Placebo
Description
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.
Time Frame
1, 3, 5 and 7 hours post dose
Title
Mean Score on SDLP Driving Test for Participants Taking Modafinil Versus Placebo
Description
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.
Time Frame
2, 4 and 6 hours post dose
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:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
24122944
Citation
Sun H, MacLeod C, Mostoller K, Mahon C, Han L, Renger JJ, Ma J, Brown KR, Schulz V, Kay GG, Herring WJ, Lines C, Rosen LB, Murphy MG, Wagner JA. Early-stage comparative effectiveness: randomized controlled trial with histamine inverse agonist MK-7288 in excessive daytime sleepiness patients. J Clin Pharmacol. 2013 Dec;53(12):1294-302. doi: 10.1002/jcph.182. Epub 2013 Oct 4.
Results Reference
result
Learn more about this trial
Pharmacodynamics and Efficacy of MK-7288 in Adults With Sleep Apnea (MK-7288-010)
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