Withdrawal Study to Demonstrate the Maintenance Effect in the Treatment of Non-24-Hour Sleep-Wake Disorder
Condition: Non-24-Hour Sleep-Wake Disorder
MeSH terms: Sleep Wake Disorders; Sleep Disorders, Circadian Rhythm
Intervention: tasimelteon; Placebo
Intervention description: 20 mg tasimelteon capsules, daily; Placebo capsules, daily
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Healthy volunteers: No
Keywords: Blindness; Eye Diseases; Nap Disorders; Circadian Rhythm Disorders; Sleep Disorders; Circadian Rhythm Sleep Disorders; Dyssomnias; Nervous System Diseases

Summary:

      The purpose of this study is to evaluate the maintenance effect and safety of 20 mg
      tasimelteon versus placebo in subjects suffering from Non-24-Hour Sleep-Wake Disorder.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Ability and acceptance to provide informed consent;

          2. Males, non-fecund females (i.e., surgically sterilized, if procedure was done 6 months
             before screening or subject is postmenopausal, without menses for 6 months before
             screening), or females of child-bearing potential using an acceptable method of birth
             control for a period of 35 days before the first dosing and must have a negative
             pregnancy test at the screening and baseline visits; Note: Women using hormonal
             methods of birth control must use an additional method of birth control during the
             study and for one month after the last dose.

          3. Willing and able to comply with study requirements and restrictions including a
             commitment to a fixed 9-hour sleep opportunity during the study;

          4. Diagnosis of N24HSWD in a previous clinical trial as measured by a tau value of > 24.1
             and the lower bound of the 95% CI is > 24.

        Exclusion Criteria:

          1. History (within the 12 months prior to screening) of psychiatric disorders including
             Major Depressive Disorder, Generalized Anxiety Disorder, Axis II Disorders, delirium
             or any other psychiatric disorder, that is not being successfully treated or has not
             been resolved and that in the opinion of the clinical investigator would affect
             participation in the study or full compliance with study procedures;

          2. History of intolerance and/or hypersensitivity to melatonin or melatonin agonists;

          3. History of drug or alcohol abuse as defined in DSM-IV, Diagnostic Criteria for Drug
             and Alcohol Abuse, within the 12 months prior to screening and/or regular consumption
             of alcoholic drinks (> 2 drinks/day or > 14 drinks/week);

             a. Note: A standard drink is equal to 13.7 grams (0.6 ounces) of pure alcohol or

               -  12-ounces of beer

               -  8-ounces of malt liquor

               -  5-ounces of wine

               -  1.5-ounces or a "shot" of 80-proof distilled spirits or liquor (e.g., gin, rum,
                  vodka, or whiskey);

          4. Subject is at risk of suicide, in the opinion of the Investigator. Evidence of suicide
             risk could include any suicide attempt within the past year or any other suicidal
             behavior within the past year;

          5. Current clinically significant cardiovascular, respiratory, neurologic, hepatic,
             hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently
             controlled and stable;

          6. Subjects who have estimated creatinine clearance (CLcr; based on the Cockcroft-Gault
             equation) ≤ to 55 mL/min;

          7. Clinically significant deviation from normal in clinical laboratory results, vital
             signs measurements, or physical examination findings at screening as determined by the
             clinical investigator;

          8. Indication of impaired liver function (values for AST, ALT or bilirubin > 2 times
             Upper Limit of Normal);

          9. Pregnant or lactating females;

         10. A positive test for drugs of abuse at the screening visit; Note: A positive drug
             screen at Visit 1 needs to be discussed with the medical monitor and will be evaluated
             on a case-by-case basis.

         11. Smoke more than 10 cigarettes/day;

         12. Worked night, rotating, or split (period of work, followed by break, and then return
             to work) shift work within 1 month of the screening visit or plan to work these shifts
             during the study;

         13. Unwilling or unable to follow the medication restrictions described in Section 8.2.,
             or unwilling or unable to sufficiently wash-out from use of a restricted medication

         14. Unable to perform calls to the study IVR system to report questionnaire results;

         15. Any other sound medical reason as determined by the clinical investigator;

         16. Legal incompetence or limited legal competence, detainment in an institution for
             official or legal reasons.