A study comparing 20 mg tasimelteon and placebo in the treatment of blind individuals with no light perception having problems in synchronizing their internal clock with the 24- hour light-dark cycle

• Conditions: Blind males or females with no conscious light perception and the complaint of a sleep-wake disorder associated with Non-24 Hour Sleep-Wake Disorder.; MedDRA version: 14.1Level: PTClassification code 10009191Term: Circadian rhythm sleep disorderSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Body processes [G] - Biological Phenomena [G16]

• Registration Number: EUCTR2011-000281-35-DE
• Lead Sponsor: Vanda Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-03-02
• Last Update Posted: 7 January 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 84

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 (i.e., surgically sterilized, if procedure was done 6 months before screening or subject is postmenopausal, without menses for 1 year before screening), or females of child-bearing potential using 2 independent barrier methods of birth control (i.e., condoms, diaphragm, spermicidal agents, cervical cap) for a period of 35 days before the first dosing, during the study and for one month after the last dose and must have a negative at the screening and baseline visits;
Note: Hormonal contraception is not considered a reliable method of birth control in this study.
Note: For patients over 55 years of age at the screening visit absence of menses for 1 year before screening is sufficient to establish the postmenopausal status. The postmenopausal status of a patient under 55 years of age at the screening visit will be confirmed by measuring the following hormones:
Follicle-stimulating hormone (FSH) =40 mIU/mL
Estradiol = 30 pg/mL (110.1 pmol/L)
5. Willing to comply with study requirements and restrictions including commitment to a fixed 9-hour sleep opportunity during the study;
6. Fluent in English or German respectively;
7. No perception of light by the subject’s own report;
8. Tau length of = 24.25 and the lower bound of 95% CI > 24.0 and the upper bound of 95% CI < 24.9 based on urinary aMT6s rhythms;
9. Diagnosis of N24HSWD as determined by:
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 and
b. Urinary aMT6s demonstrates a progressive delay of the aMT6 acrophase time.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

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. Subjects who take NSAIDs daily and would not interrupt their use for the 48-hour urine collections and the 24 hours preceding them;
4. History of intolerance and/or hypersensitivity to melatonin or melatonin agonists;
5. 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
o 12-ounces of beer
o 8-ounces of malt liquor
o 5-ounces of wine
o 1.5-ounces or a shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey);
6. Subjects having any suicidal ideation of type 4 or 5 on the C-SSRS at Screening or Baseline;
7. 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;
8. Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable;
9. Subjects who have estimated creatinine clearance (CLcr; based on the Cockcroft-Gault equation) = to 55 mL/min;
10. 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;
11. Indication of impaired liver function (values for AST, ALT or bilirubin > 2 times Upper Limit of Normal);
12. Pregnant or lactating females;
13. 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.
14. Smoke more than 10 cigarettes/day;
15. 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;
16. Participation in a previous tasimelteon (aka VEC-162 or BMS-214778) trial;
17. Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever was longer) of screening;
18. 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
19. Use of melatonin or melatonin agonist within 1 week of the tau identification segment;
20. Unable to perform calls to the study IVR system to report questionnaire results;
21. Any other sound medical reason as determined by the clinical investigator.
22. Legal incompetence or limited legal competence, detainment in an institution for official or legal reasons.

Study & Design

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