Apnea, Sleep
Conditions
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).
Interventions
DRUGPlacebo to modafinil
two 100 mg tablets, orally, single dose
DRUGMK-7288
one or two 10 mg capsules, orally, single dose
DRUGPlacebo to MK-7288
one or two capsules, orally, single dose
DRUGModafinil
two 100 mg tablets, orally, single dose
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Sleep Latency Score on the Maintenance of Wakefulness Test (MWT) for Participants Taking MK-7288 Versus Placebo | 1, 3, 5 and 7 hours post dose | 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 | 2, 4 and 6 hours post dose | 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) | Up to 36 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Mean Sleep Latency Score on the MWT for Participants Taking MK-7288 Versus Modafinil | 1, 3, 5 and 7 hours post dose | 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 | 1, 3, 5 and 7 hours post dose | 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 | 2, 4 and 6 hours post dose | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All participants who were randomized in the study. | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Washout Period 1 | Adverse Event | 0 | 1 | 0 | 0 |
| Washout Period 1 | Noncompliance with nCPAP | 1 | 0 | 0 | 0 |
| Washout Period 2 | Adverse Event | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Continuous | 50.0 Years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 54 | 29 / 55 | 12 / 53 | 5 / 52 |
| serious Total, serious adverse events | 1 / 54 | 1 / 55 | 0 / 53 | 0 / 52 |
Outcome results
Primary
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.
Time frame: 2, 4 and 6 hours post dose
Population: The PP population consisted of all participants who were compliant with the protocol and had available data from at least one treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-7288 10 mg | Mean Score on Standard Deviation of Lane Position (SDLP) Driving Test for Participants Taking MK-7288 Versus Placebo | 0.31 Meters |
| MK-7288 20 mg | Mean Score on Standard Deviation of Lane Position (SDLP) Driving Test for Participants Taking MK-7288 Versus Placebo | 0.32 Meters |
| Modafinil 200 mg | Mean Score on Standard Deviation of Lane Position (SDLP) Driving Test for Participants Taking MK-7288 Versus Placebo | 0.32 Meters |
| Placebo | Mean Score on Standard Deviation of Lane Position (SDLP) Driving Test for Participants Taking MK-7288 Versus Placebo | 0.39 Meters |
Comparison: Difference in LS means95% CI: [-0.1, -0.05]
Comparison: Difference in LS means95% CI: [-0.09, -0.05]
Primary
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.
Time frame: 1, 3, 5 and 7 hours post dose
Population: The Per-Protocol (PP) population consisted of all participants who were compliant with the protocol and had available data from at least one treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-7288 10 mg | Mean Sleep Latency Score on the Maintenance of Wakefulness Test (MWT) for Participants Taking MK-7288 Versus Placebo | 18.66 Minutes |
| MK-7288 20 mg | Mean Sleep Latency Score on the Maintenance of Wakefulness Test (MWT) for Participants Taking MK-7288 Versus Placebo | 18.62 Minutes |
| Modafinil 200 mg | Mean Sleep Latency Score on the Maintenance of Wakefulness Test (MWT) for Participants Taking MK-7288 Versus Placebo | 20.71 Minutes |
| Placebo | Mean Sleep Latency Score on the Maintenance of Wakefulness Test (MWT) for Participants Taking MK-7288 Versus Placebo | 10.50 Minutes |
Comparison: Difference in least squares (LS) means95% CI: [6.11, 10.2]
Comparison: Difference in LS means95% CI: [6.07, 10.15]
Primary
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.
Time frame: Up to 36 days
Population: All Participants as Treated (APaT) population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-7288 10 mg | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | Clinical AE | 30 Participants |
| MK-7288 10 mg | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | Laboratory AE | 1 Participants |
| MK-7288 20 mg | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | Laboratory AE | 1 Participants |
| MK-7288 20 mg | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | Clinical AE | 37 Participants |
| Modafinil 200 mg | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | Clinical AE | 16 Participants |
| Modafinil 200 mg | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | Laboratory AE | 0 Participants |
| Placebo | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | Clinical AE | 12 Participants |
| Placebo | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | Laboratory AE | 1 Participants |
Secondary
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.
Time frame: 2, 4 and 6 hours post dose
Population: The PP population consisted of all participants who were compliant with the protocol and had available data from at least one treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-7288 10 mg | Mean Score on SDLP Driving Test for Participants Taking Modafinil Versus Placebo | 0.31 Meters |
| MK-7288 20 mg | Mean Score on SDLP Driving Test for Participants Taking Modafinil Versus Placebo | 0.32 Meters |
| Modafinil 200 mg | Mean Score on SDLP Driving Test for Participants Taking Modafinil Versus Placebo | 0.32 Meters |
| Placebo | Mean Score on SDLP Driving Test for Participants Taking Modafinil Versus Placebo | 0.39 Meters |
Comparison: Difference in LS means90% CI: [-0.08, -0.05]
Secondary
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.
Time frame: 1, 3, 5 and 7 hours post dose
Population: The PP population consisted of all participants who were compliant with the protocol and had available data from at least one treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-7288 10 mg | Mean Sleep Latency Score on the MWT for Participants Taking MK-7288 Versus Modafinil | 18.66 Minutes |
| MK-7288 20 mg | Mean Sleep Latency Score on the MWT for Participants Taking MK-7288 Versus Modafinil | 18.62 Minutes |
| Modafinil 200 mg | Mean Sleep Latency Score on the MWT for Participants Taking MK-7288 Versus Modafinil | 20.71 Minutes |
| Placebo | Mean Sleep Latency Score on the MWT for Participants Taking MK-7288 Versus Modafinil | 10.50 Minutes |
Comparison: Difference in LS means90% CI: [-3.76, -0.35]
Comparison: Difference in LS means90% CI: [-3.79, -0.4]
Secondary
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.
Time frame: 1, 3, 5 and 7 hours post dose
Population: The PP population consisted of all participants who were compliant with the protocol and had available data from at least one treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-7288 10 mg | Mean Sleep Latency Score on the MWT for Participants Taking Modafinil Versus Placebo | 18.66 Minutes |
| MK-7288 20 mg | Mean Sleep Latency Score on the MWT for Participants Taking Modafinil Versus Placebo | 18.62 Minutes |
| Modafinil 200 mg | Mean Sleep Latency Score on the MWT for Participants Taking Modafinil Versus Placebo | 20.71 Minutes |
| Placebo | Mean Sleep Latency Score on the MWT for Participants Taking Modafinil Versus Placebo | 10.50 Minutes |
90% CI: [8.49, 11.92]