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: February 26, 2014
Last verified: February 2014

July 2, 2010
February 26, 2014
August 2010
November 2012   (final data collection date for primary outcome measure)
  • 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).
Subjective average total night time sleep [ Time Frame: Weeks 3-6 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01163032 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Subjective average total daytime sleep [ Time Frame: Weeks 3-6 and 23-26 ] [ Designated as safety issue: No ]
  • Subjective average total night time sleep [ Time Frame: Weeks 23-26 ] [ Designated as safety issue: No ]
  • Clinical Global Impression of Change [ Time Frame: Months 2, 4, 6, 9, 11, and 12 of treatment ] [ Designated as safety issue: No ]
  • Stabilization of phase relationship between circadian melatonin rhythm and the timing of sleep [ Time Frame: Weeks 4, 6, and 24 ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

    the recording of adverse events (AEs), clinical laboratory evaluations including endocrine hormones, vital signs, and electrocardiograms(ECGs).

    The Columbia Suicide Severity Rating Scale (C-SSRS) will be used to assess suicidal behavior and ideation.

  • Withdrawal [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    Assesment of withdrawal will be measured by the Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ)
  • Post-treatment effect [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    Subjective sleep questionnaires administered upon treatment cessation will be used to assess Post-treatment Effect.
Not Provided
Not Provided
 
Efficacy and Safety of Tasimelteon Compared With Placebo in Totally Blind Subjects With Non-24-Hour Sleep-Wake Disorder
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

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Non-24-Hour Sleep-Wake Disorder
  • Drug: tasimelteon
    20 mg tasimelteon capsules, PO daily for 6 months
    Other Name: VEC-162
  • Drug: Placebo
    Placebo capsules, PO daily for 6 months
  • Experimental: tasimelteon
    20 mg tasimelteon capsules, PO daily for 6 months
    Intervention: Drug: tasimelteon
  • Placebo Comparator: placebo
    Placebo capsules, PO daily for 6 months
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
84
November 2012
November 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany
 
NCT01163032
VP-VEC-162-3201
No
Vanda Pharmaceuticals
Vanda Pharmaceuticals
Not Provided
Study Director: Vanda Pharmaceuticals Vanda Pharmaceuticals
Vanda Pharmaceuticals
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP