Withdrawal Study to Demonstrate the Maintenance Effect in the Treatment of Non-24-Hour Sleep-Wake Disorder
|ClinicalTrials.gov Identifier: NCT01430754|
Recruitment Status : Completed
First Posted : September 8, 2011
Results First Posted : October 10, 2014
Last Update Posted : October 10, 2014
|Condition or disease||Intervention/treatment||Phase|
|Non-24-Hour Sleep-Wake Disorder||Drug: tasimelteon Drug: Placebo||Phase 3|
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 in study VP-VEC-162-3201 that meet the entry criteria for this study will be eligible for the run-in phase The run-in phase comprises a screening visit where subject's initial eligibility will be evaluated. Subjects that meet the inclusion/exclusion criteria at screening will enter the run-in phase and will be dosed with 20 mg of tasimelteon daily for 6 weeks. The tau estimation phase (48 hour urine collection samples to evaluate response to tasimelteon) will follow the run-in phase and will last approximately 6 weeks long. The randomized withdrawal phase comprises approximately eight weeks of treatment with either placebo or tasimelteon 20 mg taken approximately 1 hour prior to their target bedtime in a double-masked fashion.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized Withdrawal Study to Demonstrate the Maintenance of Effect of 20 mg Tasimelteon in the Treatment of N24HSWD|
|Study Start Date :||September 2011|
|Actual Primary Completion Date :||December 2012|
|Actual Study Completion Date :||December 2012|
20 mg tasimelteon capsules
20 mg tasimelteon capsules, daily
Other Name: VEC-162
Placebo Comparator: Placebo
Placebo capsules, daily
- Maintenance of Entrainment (aMT6s) 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 aMT6s 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01430754
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|Study Director:||Vanda Pharmaceuticals||Vanda Pharmaceuticals|