MedDRA version: 18.1 Level: PT Classification code 10040984 Term: Sleep disorder System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Trade Name: HELTLIOZ®
Product Name: Tasimelteon (HELTLIOZ®)
Product Code: VEC-162
Pharmaceutical Form: Capsule
Pharmaceutical form of th
Sponsors
Vanda Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability and acceptance to provide written informed consent 2. Men or women between 18 – 75 years, inclusive 3. Body Mass Index (BMI) of = 18 and = 30 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 6 months before screening), or females of child-bearing potential using an acceptable method 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 pregnancy test at the screening and baseline and D1 visits; 5. 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. Valid passport for international travel and fluent in English 6. In good health as determined by a medical and psychiatric history, physical examination, Electrocardiogram, and serum chemistry and hematology 7. Willing to comply with study procedures and restrictions with fixed sleep time and wake time during the study and to attend regularly scheduled clinic visits as specified in this protocol 8. Has negative urine test result for selected substances of abuse at V2- through the end of the randomization phase 9. Has not used pharmacological sleep assistance more than 4 times/month during the 3 months prior to screening 10. Must have discontinued use of all pharmacological sleep aids beginning 1 week prior to Visit 2 and for the duration of the trial 11. Must have a target daily bedtime that on average occurs between 21:00 and 24:00 12. History of sleep disturbances associated with jet lag symptoms at least once in the last five years, as defined in the International Classification of Sleep Disorders (ICSD-3) 13. Must have =60% Sleep Efficiency during the first two thirds of the 8-hour sleep period after a 5-8 hour phase advance of their sleep-wake schedule conducted during a diagnostic PSG while in screening 14. Actigraphy must demonstrate, on average, that the total sleep time each night is between 7 to 9 hours during screening 15. Actigraphy must demonstrate, on average, the subject’s habitual bedtime does not differ by more than 2 hours during screening 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 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1. History of primary insomnia or any circadian rhythm sleep disorder, other than jet lag, as defined by ICSD-3 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. Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable 4. History of intolerance and/or hypersensitivity to melatonin or melatonin agonists 5. Indication of impaired liver function (values for enzymes aspartate transaminase (AST) and alanine transaminase (ALT) or bilirubin > Upper Limit of Normal) 6. 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 7. Major surgery, trauma (including broken pelvis/legs), illness (e.g. sepsis, stroke) or immobile for 3 or more days within the past month 8. Current smoker or quit smoking within the last 30 days 9. Active cancer or cancer treatment within the past 6 months 10. Central venous catheter in place or within the past month 11. History of pulmonary embolism /deep vein thrombosis (DVT) or short term blood thinner treatment as an outpatient (e.g. Coumadin, Lovenox, heparin) 12. History or family history of thrombosis or hypercoagulable state (e.g. Factor V Leiden, Factor VIII deficiency, Protein C & S deficiency) 13. Pregnancy or recent pregnancy (within 6 weeks) 14. History of restless leg syndrome, sleep apnea, or periodic limb movement disorder and or have current diagnosis as confirmed by the diagnostic PSG at V2 15. Habitual bedtime varies by more than two hours, on average 16. History or evidence of excessive daytime sleepiness as determined by a score of more than 10 on the Epworth Sleepiness Scale; 17. History of drug or alcohol abuse as defined in DSM-V, 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) 18. Traveled more than three time zones 2 weeks prior to the screening visit until the travel period. 19. Traveled outside the origination time zone within 1 week before the end of the screening period. 20. An average bedtime that varies more than 2 hours per week than the target bedtime during the weeks between the diagnostic PSG and the baseline visit based on patient reported sleep diaries and actigraphy. 21. 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. 22. Participation in a previous tasimelteon (aka VEC-162 or BMS-214778) trial 23. Use of any investigational drug, including placebo, central nervous system medication, or any other prescription or OTC medication tha
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess the effects of tasimelteon 20 mg on nighttime sleep parameters as measured by Polysomnography (PSG) after transmeridian travel on the worst night. - Step-down Primary: To assess the effects of tasimelteon 20 mg as measured by the reduction in the proportion of patients with disturbed sleep after transmeridian travel on the worst night ; Secondary Objective: Key secondary objectives: 1. To evaluate tasimelteon 20 mg for treatment of excessive daytime sleepiness associated with Jet Lag Disorder due to transmeridian travel as measured by Maintenance of Wakefulness Test (MWT). 2. To assess the effects of tasimelteon 20 mg on subjective assessments of daytime sleepiness as measured by the Karolinska Sleepiness Scale (KSS) on the worst day. 3. To assess the effects of tasimelteon 20 mg on objective assessments of Latency to Persistent Sleep (LPS) on the worst night. ; Primary end point(s): The primary efficacy endpoint is defined as the first two thirds of the night (TST2/3) on the worst of 3 nights of sleep calculated from Total Sleep Time as measured by polysomnography. The primary null hypothesis is that there is no difference in TST2/3 between subjects receiving tasimelteon and subjects receiving placebo. TST2/3 will be assessed by analysis of covariance, with treatment group, clinical site, baseline and time zone as a main effect. The primary efficacy analysis will be based on the ITT population. If the primary null hypothesis is rejected at an alpha level of 0.05, then the step-down primary null hypothesis will also be tested at an alpha level of 0.05 to assess the efficacy of tasimelteon versus placebo as measured by the reduction in the proportion of patients with disturbed sleep on the worst night. The step-down primary endpoint will be summarized and analyzed by a two-sided unconditional exact test, B | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary/secondary efficacy outcomes include: • MWT score • PGI-S score • TSTfn, LPS, SE and WASO as measured by PSG • TSTs, SL, SQs as measured by Sleep Diaries KSS score • JLQ score For the continuous key secondary or secondary efficacy variables, descriptive statistics will be presented by treatment group, and the scores will be summarized and analyzed in a manner similar to that for the primary endpoint. Categorical variables will also be summarized and evaluated. Details of the analysis and the multiplicity adjustment for the key secondary endpoints and analysis will be described in the SAP. | — |
Countries
France, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactSenior Director
Medpace UK
Outcome results
None listed