Open-label safety study of a 1-year 20 mg dose regimen of tasimelteon for the treatment of Non-24-Hour Sleep-Wake Disorder (N24HSWD) in blind individuals with no light perception.

• Conditions: on-24 Hour Sleep-Wake Disorder; MedDRA version: 12.1Level: LLTClassification code 10013419Term: Disruptions of 24 hour sleep-wake cycle

• Registration Number: EUCTR2010-020912-12-FR
• Lead Sponsor: Vanda Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-12
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Ability and acceptance to provide informed consent;
2.Men or women between 18 – 75 years, inclusive;
3.Body Mass Index (BMI) of = 18 and = 33 kg/m2 (BMI = weight (kg)/ [height (m)]2);
4.Males, non-fecund females, or females of child-bearing potential ( defined as less than 1 year post-menopausal or not surgically sterile ) must be using an acceptable method of birth control (e.g., oral contraceptives, patch, intrauterine device [IUD], diaphragm or condom with spermicidal jelly or foam or abstinence, or cervical cap) for a period of 35 days before the first dosing and must have a negative pregnancy test at the screening and baseline visits;
5.Note: Women using hormonal methods of birth control (e.g. oral contraceptives, patch, and steroids) must use an additional method of birth control during the study and for one month after the last dose.
6.Willing and able to comply with study requirements and restrictions;
7.No perception of light by the patient’s own report;
8.Diagnosis of N24HSWD
a.History (within the last 3 months) of trouble sleeping at night (difficulty initiating sleep or staying asleep), difficulty awakening in the morning, or daytime sleepiness as determined by answering yes to at least one question in the Sleep Complaint Questionnaire;
b.An abnormal phase relationship between the circadian melatonin rhythm and their target sleep-wake cycle is established per urinary aMT6s assessment.
9. Affiliated with or beneficiary of a social security system

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Have a probable diagnosis of a current sleep disorder other than N24HSWD that is the primary cause of the sleep disturbance based on clinical investigator medical judgment;
2. 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 in the opinion of the clinical investigator would affect participation in the study or full compliance with study procedures;
3. History of intolerance and/or hypersensitivity to melatonin or melatonin agonists;
4. 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 (> 40g/day);
5. Patients having any current suicidal ideation of type 4 or 5 on the C-SSRS at Screening or Baseline;
6. Patient 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;
7. Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable;
8. Patients who have estimated creatinine clearance (CLcr; based on the Cockcroft-Gault equation) = to 55 mL/min;
9. Clinically significant deviation from normal in clinical laboratory results, vital signs measurements, or physical examination findings at screening or baseline as determined by the clinical investigator;
10. Indication of impaired liver function (values for AST, ALT or bilirubin > 2 times Upper Limit of Normal);
11. Pregnant or lactating females;
12. A positive test for drugs of abuse at the screening visit;
13. Smoke more than 10 cigarettes/day;
14. Participation in a previous tasimelteon (aka VEC-162 or BMS-214778) trial;
15. Exposure to any investigational drug, including placebo, within 30 days, 5 half-lives, or the exclusion period given by a previous study in which the patient has participated in, whichever of the three scenarios is longer.
16.Use of central nervous system prescription or OTC medications, other than melatonin, that affects the sleep-wake cycle within 3 weeks or 5 half-lives (whichever was longer) of Baseline;
17. Use of melatonin or melatonin agonist within 1 week of the urine collection for the aMT6s assessment;
18. Any other sound medical reason as determined by the clinical investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To characterize the effect of tasimelteon, 20 mg/night for 52 weeks, on standard measures of patients' safety. ;Primary end point(s): Adverse events including suicidal ideation or behavior, changes in vital signs, clinical laboratory evaluations, electrocardiograms and physical exam findings during treatment. ;Secondary Objective: To assess the effect of tasimelteon on patient reported nighttime sleep as measured by a Patient Global Impression of Change (PGI-C). <br><br>To assess the effect of tasimelteon on daytime naps as measured by Patient Global Impression of Change (PGI-C). <br><br>To assess the effects of tasimelteon as measured by a Clinical Global Impression of Change (CGI-C).