Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

Condition(s) targeted: Healthy Volunteers

Intervention: Almorexant (Drug); Almorexant (Drug); Zolpidem 10mg (Drug); Placebo (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Northern California Institute of Research and Education

Official(s) and/or principal investigator(s):
Thomas Neylan, M.D., Principal Investigator, Affiliation: Northern California Institute of Research and Education

Overall contact:
Mindy Sivasubramanian, M.S., Phone: 888-308-1807, Email: sleepaidstudy@ncire.org

In recent years, there has been increased focus on cognitive side effects of sleep-inducing medications that may contribute to unusual behavior during unexpected awakenings during the night. Concerns regarding these side effects have led to a class Food and Drug Administration (FDA) warning for all sleep-inducing medications. Almorexant is an experimental sleep-inducing medication in a new class of medications that is being extensively developed by multiple pharmaceutical companies. Medications in this class block wake/arousal centers in the brain that function with proteins called hypocretins. The goal of this study is to evaluate the impact on cognitive performance of almorexant vs. zolpidem (an approved sleep aid) or placebo.

Official title: Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Primary outcome: A comparison between dosing groups on performance on neurocognitive measures

Detailed description: Up to 216 healthy volunteers will be enrolled to participate in the 10 day study. After

screening procedures have been completed (at SFVAMC), Days 1 - 7 will take place in

subjects' homes, where their sleep/wake activity will be monitored. Days 8 - 10 will take

place at Moffitt Hospital. On Day 10, subjects will take one dose of either almorexant 100mg, almorexant 200mg, zolpidem 10mg, or placebo. Cognitive tests will be administered to

subjects throughout Day 10. Subjects will return for follow-up safety labs within 5 - 12

days of dosing with study medication. Based on animal studies, it is anticipated that subjects who take almorexant will be less cognitively impaired than those who take zolpidem.

Minimum age: 19 Years. Maximum age: 39 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Physically healthy male and female subjects between the ages of 18 and 39

- Typical bedtime between 10pm and 12am; typical wake time between 6am and 8am

- Body Mass Index (BMI) >18 and < 28 kg/m2;

Exclusion Criteria:

- Diagnosis of a sleep disorder within two years of screening or currently

- Sleep Apnea

- A current or lifetime diagnosis of any psychiatric disorder with psychotic features,

major depression, bipolar disorder, panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, dysthymia, or agoraphobia without panic disorder

- A current diagnosis of alcohol or substance abuse or dependence or a history of

alcohol or substance abuse or dependence within the past year

- Subjects who are pregnant, lactating, or planning to become pregnant or subjects who

are not willing to use an acceptable form of birth control during the study;

- Lifetime history of brain injury (including concussions, mild traumatic brain

injuries, or loss of consciousness for ≥ 10 minutes which resulted in the development of persistent symptoms lasting ≥ 1 month), stroke, brain hemorrhage, seizures (not including infantile febrile seizures), epilepsy, or brain infection caused by meningitis, encephalitis, or any other infectious agent.

- Systemic illness affecting central nervous system (CNS) function;

- Cardiovascular disease (to include but not limited to arrhythmias, valvular heart

disease, congestive heart failure, myocardial infarction or family history of sudden cardiac death), hypertension, or hypercholesterolemia;

- Asthma or other reactive airway diseases;

- Hepatic impairment (Child-Pugh A, B, C);

- Any other chronic or unstable medical conditions;

- Current use of statins, ketoconazole, prescription or over-the-counter medications or

herbal supplements containing psychoactive properties or stimulants in the judgment of the Investigator-Sponsor or Medical Monitor;

- Treatment with another investigational drug;

- Current daily use of any other medication unless specifically approved by the

Principal Investigator;

- Consumption of grapefruit (including grapefruit juice) or treatment with moderate or

strong inhibitors of cytochrome P450 3A4 (CYP3A4) within one week prior to randomization;

- Treatment with drugs metabolized by CYP2D6 isoenzyme with a narrow therapeutic index

within one week prior to randomization;

- Self-reported regular nicotine use within the past 30 days involving > 4 cigarettes

per week or > 2 cigarettes per day;

- Self-reported consumption of alcohol within the past 30 days of >14 standard drinks

per week or ≥ 5 standard drinks on any day (men), or > 7 standard drinks per week or ≥ 4 standard drinks on any day (women).

- Use of opioids, benzodiazepines, amphetamines, cocaine, cannabis, or any other

illicit drugs within 30 days of screening by self report or a urine toxicology screen;

- Known liver disease or abnormal liver function tests assessed at the time of

screening;

- Self-reported regular caffeine use in excess of 200 mg per day on average within six

months of screening;

- Habitual long sleepers ( > 9 hours) or short sleepers (< 5 hours);

- Shift work within one month prior to the screening visit or planned shift work during

the study;

- Travel of > 3 time zones within one week prior to the screening visit or any other

visit;

- Known hypersensitivity or contraindication to any excipients of the drug formulation.

Mindy Sivasubramanian, M.S., Phone: 888-308-1807, Email: sleepaidstudy@ncire.org

San Francisco Veterans Affairs Medical Center, San Francisco, California 94121, United States; Recruiting
Thomas Neylan, M.D., Principal Investigator

Starting date: May 2011
Last updated: August 11, 2011