Safety and Efficacy Study of Dronabinol to Treat Obstructive Sleep Apnea

Study Overview
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Brief Summary
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This is a proof of concept study to determine the safety and efficacy of dronabinol for the treatment of obstructive sleep apnea syndrome (OSA).

Official Title
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Cannabimimetic Treatment of Obstructive Sleep Apnea: A Proof of Concept Trial

Conditions
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Sleep Apnea, Obstructive

Intervention / Treatment
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* Drug: Dronabinol
* Drug: Placebo (for Dronabinol)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult 21 to 64 years of age; 15≤AHI ≤ 50 on screening polysomnogram (PSG) ESS score ≥ 7 Able to understand and complete informed consent and all study assessments and forms, presented in an English-speaking format; Women of child-bearing potential (WCBP) must have a negative urine pregnancy test. In addition sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable or implantable hormonal contraceptive; tubal ligation; intra-uterine devices; barrier contraceptive with spermicide; or vasectomized partner). Exclusion Criteria: Arterial oxygen saturation < 75% for > 5% of sleep period time on screening PSG; Occupation or life situation that may impart risk by study participation (e.g. commercial driver, pilot, police officer, fireman); Motor vehicle accident or near-miss related to sleepiness (self-report) within 2 years of the first dose of study drug (Day 8); Body mass index > 45 kg/m2 Severe obstructive sleep apnea syndrome (OSAS) that, based on the clinical judgment of the Investigator, precludes delaying positive airway pressure treatment; History of shift work or rotating shifts within the month prior to the first dose of study drug (Day 8); Prior upper airway surgery for snoring or OSAS as an adult (≥ 18 years of age); Prior non-invasive treatment for OSAS within 6 months prior to the first dose of study drug (Day 8); Major surgery within 6 months prior to the first dose of study drug (Day 8); Bariatric surgery within 2 years prior to the first dose of study drug (Day 8). If post-bariatric surgery, weight must be stable ±5% (self-report) for at least 6 months prior to first dose of study drug (Day 8). Any form of medically managed weight loss program within 6 months prior to the first dose of study drug (Day 8); Significant defect in nasal patency due to anatomical abnormalities or uncontrolled or recurrent episodes of rhinitis; Any clinically significant unstable or progressive medical condition; Any primary sleep disorder other than OSAS as determined by history, physical examination, or Visit 2 PSG (after 7-day screening run-in period); Clinically significant or uncontrolled: chronic obstructive pulmonary disease (COPD), cardiovascular disease, gastrointestinal, respiratory, pancreatic, hepatic, renal, hematologic, endocrine [including insulin-dependent diabetes mellitus (IDDM)], neurological, urogenital, connective tissue, dermatological, thyroid, or other medical disorder; Any clinically significant psychiatric disorder; History of seizure disorder; Treatment with any prescription antidepressant medication within 1 month prior to the first dose of study drug (Day 8); Treatment with sedatives, hypnotics or other psychoactive drugs within 30 days prior to the first dose of study drug (Day 8); Any complete blood count (CBC) or liver function test (LFT) laboratory value outside the normal range which, in the clinical judgment of the Investigator renders a subject inappropriate for randomization to treatment; Pregnancy [as demonstrated by positive urine human chorionic gonadotropin (hCG) test] or lactation; Allergic to cannabinoids or sesame oil; History of substance abuse (including alcohol abuse or dependence) or laboratory evidence of drug abuse on the Visit 1 drug-screening panel; Use of dietary supplements which in the judgment of the Investigator may impact sleep or breathing behaviors; Average daily caffeine consumption > 500 mg/day ( 5 cups of coffee); Average weekly alcohol consumption > 10 units; Unwillingness to abstain from caffeine and alcohol on all days when overnight or daytime testing will be performed; Participation in any other investigational protocol within the 30 days prior to the first dose of study drug (Day 8); Any condition which, in the opinion of the Investigator, places the patient at unacceptable risk if he or she were to participate in the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar Pill<br>Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in | Drug: Placebo (for Dronabinol)<br> <br> |
| Experimental: 2.5 mg/day<br>Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in | Drug: Dronabinol<br> <br> |
| Experimental: 10 mg/day<br>Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation | Drug: Dronabinol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Apnea/Hypopnea Index (AHI) | Change in AHI derived as: AHI (end of treatment) minus AHI (pre-treatment) | Baseline and Week 6 | 
| Change in Epworth Sleepiness Scale (ESS) | Change in ESS derived as: ESS (end of treatment) minus ESS (pre-treatment). The ESS scale has a range of 0 to 24, with 0 representing the least degree of sleepiness and 24 the greatest degree of sleepiness. There are no subscales. | Baseline and Week 6 | 
| Change in Sleep Latency: Maintenance of Wakefulness Test (MWT) | Change in MWT derived as: MWT (end of treatment) minus MWT (pre-treatment). The Maintenance of Wakefulness Test measures a person's ability to stay awake in a quiet, dark and nonstimulating room for a period of time. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability by Treatment Satisfaction Questionnaire for Medications (TSQM) Overall Score. | The TSQM measures a person's satisfaction with treatment based on a 7-point scale ranging from Extremely Dissatisfied to Extremely Satisfied in response to the question, Taking all things into account, how satisfied or dissatisfied are you with this medication?. | Week 6 | 
| Adverse Events (AEs) | AEs will be evaluated and tracked throughout subject participation (up to 8 weeks) | Up to 8 weeks | 
| Change in Desaturation Time (DT) | Change in DT (total minutes with arterial oxygen saturation below 85% during 8-hour polysomnography) derived as: DT (end of treatment) minus DT (pre-treatment) | 6 weeks |