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Pharmacodynamics and Efficacy of MK-7288 in Adults With Sleep Apnea (MK-7288-010)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01092780
First received: March 23, 2010
Last updated: March 22, 2016
Last verified: March 2016
  Purpose
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).

Condition Intervention Phase
Apnea, Sleep
Drug: MK-7288
Drug: Placebo to MK-7288
Drug: Modafinil
Drug: Placebo to modafinil
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: An Active-Comparator Controlled Single Dose Study to Evaluate the Pharmacodynamics/Efficacy of MK-7288 in Sleep Apnea Patients

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Mean Sleep Latency Score on the Maintenance of Wakefulness Test (MWT) for Participants Taking MK-7288 Versus Placebo [ Time Frame: 1, 3, 5 and 7 hours post dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2, 4 and 6 hours post dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 36 days ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1, 3, 5 and 7 hours post dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1, 3, 5 and 7 hours post dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2, 4 and 6 hours post dose ] [ Designated as safety issue: No ]
    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.


Enrollment: 56
Study Start Date: May 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-7288 10mg/Pbo/MK-7288 20mg/Modafinil
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.
Drug: MK-7288
one or two 10 mg capsules, orally, single dose
Drug: Placebo to MK-7288
one or two capsules, orally, single dose
Drug: Modafinil
two 100 mg tablets, orally, single dose
Other Name: PROVIGIL®
Drug: Placebo to modafinil
two 100 mg tablets, orally, single dose
Experimental: MK-7288 20mg/MK-7288 10mg/Modafinil/Pbo
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.
Drug: MK-7288
one or two 10 mg capsules, orally, single dose
Drug: Placebo to MK-7288
one or two capsules, orally, single dose
Drug: Modafinil
two 100 mg tablets, orally, single dose
Other Name: PROVIGIL®
Drug: Placebo to modafinil
two 100 mg tablets, orally, single dose
Experimental: Modafinil/MK-7288 20mg/Pbo/MK-7288 10mg
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.
Drug: MK-7288
one or two 10 mg capsules, orally, single dose
Drug: Placebo to MK-7288
one or two capsules, orally, single dose
Drug: Modafinil
two 100 mg tablets, orally, single dose
Other Name: PROVIGIL®
Drug: Placebo to modafinil
two 100 mg tablets, orally, single dose
Experimental: Pbo/Modafinil/MK-7288 10 mg/MK-7288 20mg
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.
Drug: MK-7288
one or two 10 mg capsules, orally, single dose
Drug: Placebo to MK-7288
one or two capsules, orally, single dose
Drug: Modafinil
two 100 mg tablets, orally, single dose
Other Name: PROVIGIL®
Drug: Placebo to modafinil
two 100 mg tablets, orally, single dose

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092780

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01092780     History of Changes
Other Study ID Numbers: 7288-010  MK-7288-010 
Study First Received: March 23, 2010
Results First Received: February 18, 2016
Last Updated: March 22, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Modafinil
Armodafinil
Wakefulness-Promoting Agents
Central Nervous System Stimulants
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016