Efficacy and Safety of Tasimelteon Compared With Placebo in Totally Blind Subjects With Non-24-Hour Sleep-Wake Disorder

NCT01163032 | Completed Phase 3 Results

• 1 other identifier: VP-VEC-162-3201
• Study Type: interventional
• Target: 136
• Locations: 2 countries
• Sites: 28

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

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

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients Entrained as Assessed by Urinary aMT6

  Entrainment is a measure of synchronization of the master body clock to the 24-hour day. The circadian period (τ) was calculated using urinary aMT6s collected over four 48 hour periods , collected approximately 1 week apart for 4 separate weeks, during the screening and month 1 of the randomization phase of the trial. Entrainment was defined as having a post-baseline τ value less than 24.1 and a 95% CI that included 24.0.

  1 month

• Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 3 on N24CRS

  Clinical response is defined as the coincident demonstration of entrainment (aMT6) and a score ≥ 3 on the Non-24 Clinical Response Scale (N24CRS). N24CRS measures improvement in sleep-wake measures and overall functioning (LQ-nTST, UQ-dTSD, MoST and CGI-C). Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: \>45 minutes increase in average nighttime sleep duration; UQ-dTSD: \>45 minutes decrease in average daytime sleep duration; MoST: \>30 minutes increase and a standard deviation \<2 hours during double-masked phase (6 months); CGI-C: \<2.0 from the average of D112 and Day 183 compared to baseline For patients randomized to tasimelteon 20 mg and who also participated in the screening phase of Study 3203 (month 7 of treatment), the screening τ from Study 3203 was used if the patient did not become entrained in Study 3201 but did become entrained during the screening phase of Study 3203.

  6 months

Secondary Outcomes (7)

• Proportion of Patients Entrained as Assessed by Urinary Cortisol

  1 month

• Average Clinical Global Impression of Change (CGI-C)

  Day 112 and 183

• Proportion of Responders With a Combined Sleep/Wake Response for LQ-nTST (≥ 90 Minutes) and UQ-dTSD (≤ 90 Minutes)

  6 months

• Average Lower Quartile of Nights of Nighttime Total Sleep Time (LQ-nTST)

  6 months

• Average Upper Quartile of Days of Subjective Daytime Sleep Duration (UQ-dTSD)

  6 months

Other Outcomes (3)

• Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 2 on N24CRS

  6 months

• Proportion of Patients With a Clinical Response (Score of ≥ 3 on N24CRS)

  6 months

• Proportion of Patients With a Clinical Response (Score of ≥ 2 on N24CRS)

  6 months

Study Arms (2)

tasimelteon

EXPERIMENTAL

20 mg tasimelteon capsules, PO daily for 6 months

Drug: tasimelteon

placebo

PLACEBO COMPARATOR

Placebo capsules, PO daily for 6 months

Drug: Placebo

Interventions

tasimelteon DRUG

20 mg tasimelteon capsules, PO daily for 6 months

Also known as: VEC-162

tasimelteon

Placebo DRUG

Placebo capsules, PO daily for 6 months

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanda Pharmaceuticals: lead

Study Sites (28)

Pulmonary Associates, PA

Phoenix, Arizona, 85006, United States

Location

SDS Clinical Trials Inc.

Orange, California, 92868, United States

Location

VA Palo Alto Health Care System/PAIRE (San Fransisco Bay Area)

Palo Alto, California, 94304, United States

Location

St. Johns Sleep Disorder Center - St. Johns Medical Plaza

Santa Monica, California, 90404, United States

Location

Radiant Research - Denver

Denver, Colorado, 80239, United States

Location

PAB Clinical Research Inc.

Brandon, Florida, 33511, United States

Location

Kendall South Medical Center, Inc.

Miami, Florida, 33175, United States

Location

Ocean Sleep Disorders Center - Ormond Beach

Ormond Beach, Florida, 32174, United States

Location

Sleep Disorders Center Of Georgia

Atlanta, Georgia, 30342, United States

Location

Suburban Lung Associates SC (Chicago Metropolitan Area)

Elk Grove Village, Illinois, 60007, United States

Location

The Center for Sleep and Wake Disorders (Washington, D.C. Metropolitan Area)

Chevy Chase, Maryland, 20815, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Michigan Head-Pain Neurological Institute

Ann Arbor, Michigan, 48104, United States

Location

St. Luke's Sleep Medicine and Research Center (St. Louis Metropolitan Area)

Chesterfield, Missouri, 63017, United States

Location

New York Eye and Ear Infirmary

New York, New York, 10003, United States

Location

Tri-State Sleep Disorders Center

Cincinnati, Ohio, 45246, United States

Location

Ohio Sleep Medicine Institute (Columbus Metropolitan Area)

Dublin, Ohio, 43017, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Columbia Research Group Inc.

Portland, Oregon, 97239, United States

Location

Center For Sleep Medicine at Chestnut Hill Hospital

Philadelphia, Pennsylvania, 19118, United States

Location

Consolidated Clinical trials

Pittsburgh, Pennsylvania, 15221, United States

Location

SleepMed, Inc. - Columbia

Columbia, South Carolina, 29201, United States

Location

Todd J. Swick, M.D., P.A.

Houston, Texas, 77063, United States

Location

Advanced Sleep Research GmbH

Berlin, 10117, Germany

Location

Bergmannsheil University Hospital - Medical Clinic III

Bochum, 44789, Germany

Location

Klinische-Forschung Hannover Mitte

Hanover, 30159, Germany

Location

Universitaetsklinikum Glesen and Marburg gmbH/Schlaflabor - Sleep Lab University Marburg

Marburg, 35043, Germany

Location

Bonomed Studiezentrum

Munich, 80331, Germany

Location

Related Publications (1)

• 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.

  PMID: 26466871 DERIVED

MeSH Terms

Conditions

Sleep Disorders, Circadian Rhythm; Blindness; Eye Diseases; Chronobiology Disorders; Sleep Wake Disorders; Dyssomnias; Nervous System Diseases

Interventions

tasimelteon

Condition Hierarchy (Ancestors)

Occupational Diseases; Mental Disorders; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Marlene Dressman, Ph.D.
• Organization: Vanda Pharmaceuticals Inc.

marlene.dressman@vandapharma.com

202-734-3462

Study Officials

• Vanda Pharmaceuticals

  Vanda Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 15, 2010
• Study Start: August 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: October 16, 2014
• Results First Posted: October 16, 2014

Record last verified: 2014-10

Locations

DE (5); US (23)