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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vanda Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01163032
First received: July 2, 2010
Last updated: May 20, 2013
Last verified: May 2013
History of Changes
  Purpose

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


Condition Intervention Phase
Non-24-Hour Sleep-Wake Disorder
 Drug: tasimelteon
Drug: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Vanda Pharmaceuticals:

Primary Outcome Measures:
  • To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the proportion of entrainment. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    To determine the efficacy of tasimelteon in entraining the endogenous circadian melatonin rhythm to the 24 hour period in patients with N24HSWD.

  • To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the proportion of responders. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    (A step-down objective)To determine the efficacy of tasimelteon in subjects that are both entrained and have a significant improvement from screening in key clinical measure(s).


Secondary Outcome Measures:
  • To determine the efficacy of tasimelteon in improving subjective nighttime total sleep time (nTST) in subjects withN24HSWD [ Time Frame: circadian cycle ] [ Designated as safety issue: No ]
  • To determine the efficacy of tasimelteon in reducing subjective daytime sleep duration in subjects withN24HSWD [ Time Frame: circadian cycle ] [ Designated as safety issue: No ]
  • To assess the effects of tasimelteon to treat N24HSWD as measured by a Clinical Global Impression of Change (CGI-C). [ Time Frame: Monthly ] [ Designated as safety issue: No ]
  • To assess the effect of tasimelteon on measures of endocrine function. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • To explore the safety and tolerability of multiple oral doses of tasimelteon. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Subtype 1: To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the proportion of subtype I responders. [ Time Frame: circadian cycle ] [ Designated as safety issue: No ]
    Subtype I responders are defined as individuals whose endogenous circadian melatonin rhythm is entrained to the 24 hour period and have a significant improvement from screening in the lower quartile of nights of subjective nighttime total sleep time.

  • Subtype II: To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the proportion of subtype II responders. [ Time Frame: circadian cycle ] [ Designated as safety issue: No ]
    Subtype II responders are defined as individuals whose endogenous circadian melatonin rhythm is entrained to the 24 hour period and have a significant improvement from screening in the upper quartile of days of subjective daytime sleep duration.

  • Subtype III: To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the proportion of subtype III responders [ Time Frame: circadian cycle ] [ Designated as safety issue: No ]
    Subtype III responders are defined as individuals whose endogenous circadian melatonin rhythm is entrained to the 24 hour period and have a significant improvement from screening in the midpoint of sleep timing.

  • Subtype IV: To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the proportion of subtype IV responders. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Subtype IV responders are defined as individuals whose endogenous circadian melatonin rhythm is entrained to the 24 hour period and have a significant improvement from screening in the Clinical Global Impression of Change.

  • To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the proportion of entrainment as assessed by urinary cortisol. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • To assess the association between treatment response and the baseline excretion rate of urinary 6-sulfatoxymelatonin in tasimelteon-treated subjects with N24HSWD. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the change from screening in the midpoint of sleep timing. [ Time Frame: circadian cycle ] [ Designated as safety issue: No ]
  • To assess the efficacy of tasimelteon in subjects with N24HSWD as measured by the proportion of entrainment as assessed by urinary analytes under circadian control. [ Time Frame: circadian cycle ] [ Designated as safety issue: No ]

Enrollment: 84
Study Start Date: August 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tasimelteon
20 mg tasimelteon capsules, PO daily for 6 months
 Drug: tasimelteon
20 mg tasimelteon capsules, PO daily for 6 months
Other Name: VEC-162
Placebo Comparator: placebo
Placebo capsules, PO daily for 6 months
 Drug: Placebo
Placebo capsules, PO daily for 6 months

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 tau 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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01163032

  Show 31 Study Locations
Sponsors and Collaborators
Vanda Pharmaceuticals
Investigators
Study Director: Vanda Pharmaceuticals Vanda Pharmaceuticals
  More Information

No publications provided

Responsible Party: Vanda Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01163032     History of Changes
Other Study ID Numbers: VP-VEC-162-3201
Study First Received: July 2, 2010
Last Updated: May 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanda Pharmaceuticals:
Blindness
Eye Diseases
Nap Disorders
Circadian Rhythm Disorders
 Sleep disorders
Circadian Rhythm Sleep Disorders
Dyssomnias
Nervous System Diseases

Additional relevant MeSH terms:
Sleep Disorders, Circadian Rhythm
Sleep Disorders
Parasomnias
Chronobiology Disorders
Nervous System Diseases
 Dyssomnias
Occupational Diseases
Mental Disorders
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on May 23, 2013