Clinical trial NCT01163032: Efficacy and Safety of Tasimelteon Compared With Placebo in Totally Blind Subjects With Non-24-Hour Sleep-Wake Disorder
Official title: A Multicenter, Randomized, Double-Mask, Placebo-Controlled, Parallel Study to Investigate the Efficacy and Safety of 20 mg Tasimelteon Versus Placebo in Totally Blind Subjects With N24HSWD Followed by an OLE Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-24-Hour Sleep-Wake Disorder
Keywords: Blindness
Eye Diseases
Nap Disorders
Circadian Rhythm Disorders
Sleep disorders
Circadian Rhythm Sleep Disorders
Dyssomnias
Nervous System Diseases
Lead sponsor: Vanda Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-07-15
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of a six month double-mask treatment of tasimelteon or placebo in male and female subjects with Non-24-Hour Sleep-Wake Disorder

Detailed description: Non-24-Hour Sleep-Wake Disorder (N24HSWD) occurs when individuals, primarily those without light perception, are unable to synchronize their endogenous circadian pacemaker to the 24-hour light-dark cycle, and the timing of their circadian rhythm instead reflects the intrinsic period of their endogenous circadian pacemaker. As a result, the circadian rhythm of sleep-wake propensity in these individuals moves gradually later and later each day if there circadian period is \> 24 hours and earlier and earlier if \< 24 hours. These individuals will be able to sleep well at night when their sleep-wake propensity rhythm is approximately aligned with the 24-hour light-dark and social cycle. However, after a short time, the endogenous sleep-wake propensity rhythm and the 24-hour light-dark cycle will move out of synchrony with each other, and they may have difficulty falling asleep until well into the night. In addition to problems sleeping at the desired time, the subjects experience daytime sleepiness and daytime napping.

This will be a multicenter, randomized, double-masked, placebo-controlled, parallel study. The study has two phases: the pre-randomization phase followed by either the randomization phase or the open-label extension (OLE). The pre-randomization phase comprises a screening visit where subject's initial eligibility will be evaluated, a circadian period (τ) estimation segment, and a variable-length in-phase transition segment in which subjects will wait to start treatment until their circadian phase is aligned with their target bedtime. Subjects that meet all entry criteria for the study will enter the randomization phase. During the randomization phase, subjects will be asked to take either 20 mg tasimelteon or placebo approximately 1 hour prior to their target bedtime for 26 weeks in a double-masked fashion. Subjects who have a τ greater than 24.0 and meet all entry criteria but that are ineligible for the randomization phase due to their τ estimate may be given the opportunity to participate in the OLE phase. During the OLE phase, subjects will take open-label 20mg tasimelteon for 26 weeks.

Eligibility criteria: Inclusion Criteria:

* Ability and acceptance to provide informed consent;
* No perception of light by the subject's own report;
* Diagnosis of N24HSWD as determined by:

  1. 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
  2. Urinary aMT6s demonstrates a progressive delay of the aMT6 acrophase time.
* Willing and able to comply with study requirements and restrictions including a commitment to a fixed 9-hour sleep opportunity during the study;
* Fluent in English;

Exclusion Criteria:

* 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;
* Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable;
* 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;
* History of intolerance and/or hypersensitivity to melatonin or melatonin agonists;
* 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;
* Unable to perform calls to the study IVR system to report questionnaire results;
* Exposure to any investigational drug, including placebo, within 30 days or 5 half lives (whichever was longer) of screening;
* Use of central nervous system prescription or OTC medications, other than melatonin, that affects the sleep-wake cycle
* Use of melatonin or melatonin agonist

Primary outcomes:
measure: Proportion of Patients Entrained as Assessed by Urinary aMT6
timeFrame: 1 month
measure: Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 3 on N24CRS
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of Patients Entrained as Assessed by Urinary Cortisol
timeFrame: 1 month
measure: Average Clinical Global Impression of Change (CGI-C)
timeFrame: Day 112 and 183
measure: Proportion of Responders With a Combined Sleep/Wake Response for LQ-nTST (≥ 90 Minutes) and UQ-dTSD (≤ 90 Minutes)
timeFrame: 6 months
measure: Average Lower Quartile of Nights of Nighttime Total Sleep Time (LQ-nTST)
timeFrame: 6 months
measure: Average Upper Quartile of Days of Subjective Daytime Sleep Duration (UQ-dTSD)
timeFrame: 6 months
measure: Average Midpoint of Sleep (MoST)
timeFrame: 6 months
measure: Number of Patients With a Treatment Emergent Adverse Event (Open Label Extension Phase Only)
timeFrame: 6 months
Other outcomes:
measure: Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 2 on N24CRS
timeFrame: 6 months
measure: Proportion of Patients With a Clinical Response (Score of ≥ 3 on N24CRS)
timeFrame: 6 months
measure: Proportion of Patients With a Clinical Response (Score of ≥ 2 on N24CRS)
timeFrame: 6 months
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Orange
country: United States
facility: SDS Clinical Trials Inc.
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System/PAIRE (San Fransisco Bay Area)
state: California
city: Santa Monica
country: United States
facility: St. Johns Sleep Disorder Center - St. Johns Medical Plaza
state: California
city: Denver
country: United States
facility: Radiant Research - Denver
state: Colorado
city: Brandon
country: United States
facility: PAB Clinical Research Inc.
state: Florida
city: Miami
country: United States
facility: Kendall South Medical Center, Inc.
state: Florida
city: Ormond Beach
country: United States
facility: Ocean Sleep Disorders Center - Ormond Beach
state: Florida
city: Atlanta
country: United States
facility: Sleep Disorders Center Of Georgia
state: Georgia
city: Elk Grove Village
country: United States
facility: Suburban Lung Associates SC (Chicago Metropolitan Area)
state: Illinois
city: Chevy Chase
country: United States
facility: The Center for Sleep and Wake Disorders (Washington, D.C. Metropolitan Area)
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head-Pain Neurological Institute
state: Michigan
city: Chesterfield
country: United States
facility: St. Luke's Sleep Medicine and Research Center (St. Louis Metropolitan Area)
state: Missouri
city: New York
country: United States
facility: New York Eye and Ear Infirmary
state: New York
city: Cincinnati
country: United States
facility: Tri-State Sleep Disorders Center
state: Ohio
city: Dublin
country: United States
facility: Ohio Sleep Medicine Institute (Columbus Metropolitan Area)
state: Ohio
city: Oklahoma city
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Portland
country: United States
facility: Columbia Research Group Inc.
state: Oregon
city: Philadelphia
country: United States
facility: Center For Sleep Medicine at Chestnut Hill Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Consolidated Clinical trials
state: Pennsylvania
city: Columbia
country: United States
facility: SleepMed, Inc. - Columbia
state: South Carolina
city: Houston
country: United States
facility: Todd J. Swick, M.D., P.A.
state: Texas
city: Berlin
country: Germany
facility: Advanced Sleep Research GmbH
city: Bochum
country: Germany
facility: Bergmannsheil University Hospital - Medical Clinic III
city: Hannover
country: Germany
facility: Klinische-Forschung Hannover Mitte
city: Marburg
country: Germany
facility: Universitaetsklinikum Glesen and Marburg gmbH/Schlaflabor - Sleep Lab University Marburg
city: Munich
country: Germany
facility: Bonomed Studiezentrum
Study officials:
affiliation: Vanda Pharmaceuticals
name: Vanda Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Lockley SW, Dressman MA, Licamele L, Xiao C, Fisher DM, Flynn-Evans EE, Hull JT, Torres R, Lavedan C, Polymeropoulos MH. Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials. Lancet. 2015 Oct 31;386(10005):1754-64. doi: 10.1016/S0140-6736(15)60031-9. Epub 2015 Aug 4.