Clinical Trial: Withdrawal Study to Demonstrate the Maintenance Effect in the Treatment of Non-24-Hour Sleep-Wake Disorder

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Withdrawal Study to Demonstrate the Maintenance of Effect of 20 mg Tasimelteon in the Treatment of N24HSWD

Brief Summary: The purpose of this study is to evaluate the maintenance effect and safety of 20 mg tasimelteon versus placebo in subjects suffering from Non-24-Hour Sleep-Wake Disorder.

Detailed Summary:

Non-24-Hour Sleep-Wake Disorder (N24HSWD) occurs when individuals 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 is < 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. As time progresses, the endogenous circadian rhythm of sleep-wake propensity in these individuals moves further and further away from the 24-hour light-dark cycle and gradually, these individuals are unable to sleep at night and as a result experience extreme sleepiness during the daytime hours and more frequent naps with a longer duration. Eventually, the sleep-wake time moves back into alignment with the social time for sleep and the individuals sleep well at night and have decreased daytime napping. The alignment between their endogenous circadian rhythms and the 24-hour day is temporary as they are continually drifting later and later each day.

This will be a multicenter, randomized withdrawal, double-masked, placebo-controlled, parallel study. The study has three phases: the tasimelteon run-in phase, the tau estimation phase, and the randomized withdrawal phase. Subjects who have participated i
Sponsor: Vanda Pharmaceuticals

Current Primary Outcome: Maintenance of Entrainment (aMT6s) in Subjects With N24HSWD. [ Time Frame: Approximately 12 weeks ]

Original Primary Outcome: Maintenance of circadian rhythm entrainment in subjects with N24HSWD. [ Time Frame: Approximately 12 weeks ]

Current Secondary Outcome:

• Maintenance of Entrainment (Cortisol) in Subjects With N24HSWD [ Time Frame: Approximately 12 weeks ]
  Entrainment is a measure of synchronization of the master body clock to the 24-hour day. The circadian period (τ) was calculated using urinary cortisol collected over four separate 48 hour periods, approximately 1 week apart, during the run-in and randomized phases of the trial. Maintenance of entrainment is defined as the proportion of subjects who become non-entrained to a 24 hour day after randomization to tasimelteon or placebo. Non-entrainment was defined as having a post-baseline τ value ≥ 24.1 or the lower bound of the 95% CI >24.0.
• Change From Run-In in Subjective Nighttime Total Sleep Time in Lower Quartile of Days (LQ-nTST) During the Randomized Phase [ Time Frame: Approximately 12 weeks ]
  LQ-nTST measures the average nighttime sleep during the patient's worst 25% of nights (shortest total nighttime sleep) from run-in and randomized phase. The higher number indicates improvement.
• Change From Run-In in Total Daytime Sleep Duration in Lower Quartile of Days (UQ-dTSD) During the Randomized Phase [ Time Frame: Approximately 12 weeks ]
  UQ-dTSD measures the average daytime sleep during the patient's worst 25% of days (longest total daytime sleep) from run-in and randomized phase. Lower number indicates improvement.
• Change From Run-In in Midpoint of Sleep (MoST) During the Randomized Phase [ Time Frame: Approximately 12 weeks ]
  Midpoint of Sleep Timing (MoST) is the measurement of the average timing of sleep relative to bedtime. The average MoST value will trend to 0 as an individual's sleep becomes more fragmented. Improvement is defined as an increase in the average.
• Change From Run-In in Circadian Time to Relapse During the Randomized Phase [ Time Frame: Approximately 8 weeks ]
  Time to relapse is defined as a 45 minute or greater decrement in the weekly average of subjective nighttime total sleep time (nTST) compared to the Run-in Phase.

Original Secondary Outcome:

• Symptoms of withdrawal after a minimum of three months of tasimelteon treatment assessed by the Benzodiazepine Withdrawal Symptom Questionnaire. [ Time Frame: 2 weeks ]
• Number of participants with Treatment-Emergent Adverse Events [ Time Frame: 6 months ]
  Treatment-emergent adverse events (TEAEs) will be summarized by treatment group, by presenting, for each treatment group, the number and percentage of subjects having any treatment-emergent AE, having an AE in each body system, and having each individual AE.
• Number of participants with changes in Clinical Laboratory Data [ Time Frame: 6 months ]
  Standard Serum Hematology and Chemistry tests will be performed at basline and throughout the study
• Number of participants with newly occurring or worsening ECG abnormalities [ Time Frame: 6 months ]
• Number of participants with clinically notable values for Vital Signs and Body Measurements [ Time Frame: 6 months ]
• Number of participants who report a positive result for the C-SSRS [ Time Frame: 6 months ]

Dates:
Date Received: August 30, 2011
Date Started: September 2011
Date Completion:
Last Updated: October 8, 2014
Last Verified: October 2014