Trial Outcomes & Findings for Withdrawal Study to Demonstrate the Maintenance Effect in the Treatment of Non-24-Hour Sleep-Wake Disorder (NCT NCT01430754)
NCT ID: NCT01430754
Last Updated: 2014-10-10
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
20 participants
Primary outcome timeframe
Approximately 12 weeks
Results posted on
2014-10-10
Participant Flow
Patients who met the I/E criteria were treated with tasimelteon 20 mg for 6 wks during run-in. Entrained patients were randomized to tasimelteon 20 mg or placebo for the remainder of the study.
Participant milestones
| Measure |
Tasimelteon
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|
|
Run-In Phase
STARTED
|
57
|
0
|
|
Run-In Phase
Entrained - After Run-In Phase
|
24
|
0
|
|
Run-In Phase
COMPLETED
|
20
|
0
|
|
Run-In Phase
NOT COMPLETED
|
37
|
0
|
|
Randomized Phase
STARTED
|
10
|
10
|
|
Randomized Phase
COMPLETED
|
10
|
10
|
|
Randomized Phase
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Tasimelteon
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|
|
Run-In Phase
Circadian Period Ineligible
|
24
|
0
|
|
Run-In Phase
Protocol Violation
|
6
|
0
|
|
Run-In Phase
Adverse Event
|
2
|
0
|
|
Run-In Phase
Other
|
2
|
0
|
|
Run-In Phase
Withdrawal by Subject
|
2
|
0
|
|
Run-In Phase
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Withdrawal Study to Demonstrate the Maintenance Effect in the Treatment of Non-24-Hour Sleep-Wake Disorder
Baseline characteristics by cohort
| Measure |
Run-In - Not Randomized
n=37 Participants
20 mg tasimelteon capsules
tasimelteon: 20 mg capsules, daily
|
Tasimelteon (Randomized)
n=10 Participants
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo (Randomized)
n=10 Participants
Placebo capsules
Placebo: Placebo capsules, daily
|
Total
n=57 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
52.4 years
STANDARD_DEVIATION 13.18 • n=5 Participants
|
51.3 years
STANDARD_DEVIATION 12.87 • n=7 Participants
|
52.1 years
STANDARD_DEVIATION 12.01 • n=5 Participants
|
52.1 years
STANDARD_DEVIATION 12.71 • n=4 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Approximately 12 weeksEntrainment 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.
Outcome measures
| Measure |
Tasimelteon
n=10 Participants
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
n=10 Participants
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|
|
Maintenance of Entrainment (aMT6s) in Subjects With N24HSWD.
|
9 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Approximately 12 weeksEntrainment 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.
Outcome measures
| Measure |
Tasimelteon
n=10 Participants
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
n=10 Participants
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|
|
Maintenance of Entrainment (Cortisol) in Subjects With N24HSWD
|
8 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Approximately 12 weeksLQ-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.
Outcome measures
| Measure |
Tasimelteon
n=10 Participants
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
n=10 Participants
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|
|
Change From Run-In in Subjective Nighttime Total Sleep Time in Lower Quartile of Days (LQ-nTST) During the Randomized Phase
|
-6.74 minutes
Standard Error 18.986
|
-73.74 minutes
Standard Error 18.986
|
SECONDARY outcome
Timeframe: Approximately 12 weeksUQ-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.
Outcome measures
| Measure |
Tasimelteon
n=10 Participants
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
n=10 Participants
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|
|
Change From Run-In in Total Daytime Sleep Duration in Lower Quartile of Days (UQ-dTSD) During the Randomized Phase
|
-9.31 minutes
Standard Error 17.253
|
49.95 minutes
Standard Error 17.253
|
SECONDARY outcome
Timeframe: Approximately 12 weeksMidpoint 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.
Outcome measures
| Measure |
Tasimelteon
n=10 Participants
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
n=10 Participants
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|
|
Change From Run-In in Midpoint of Sleep (MoST) During the Randomized Phase
|
19.99 minutes
Standard Error 8.611
|
-16.05 minutes
Standard Error 8.611
|
SECONDARY outcome
Timeframe: Approximately 8 weeksTime 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.
Outcome measures
| Measure |
Tasimelteon
n=10 Participants
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
n=10 Participants
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|
|
Change From Run-In in Circadian Time to Relapse During the Randomized Phase
|
NA days
Circadian time to relapse never gets as low as 50% (median).
|
24.7 days
Interval 11.1 to 44.4
|
Adverse Events
Total Run-In
Serious events: 1 serious events
Other events: 16 other events
Deaths: 0 deaths
Run-In - Not Randomized
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Tasimelteon
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Total Run-In
n=57 participants at risk
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Run-In - Not Randomized
n=37 participants at risk
20 mg tasimelteon capsules
tasimelteon: 20 mg capsules, daily
|
Tasimelteon
n=10 participants at risk
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
n=10 participants at risk
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Serotonin Syndrome
|
1.8%
1/57 • Number of events 1 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/37 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Injury, poisoning and procedural complications
Procedural Pain
|
0.00%
0/57 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/37 • 1st dose to 30 days following last administration of study treatment
|
10.0%
1/10 • Number of events 1 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Nervous system disorders
Loss of Consciousness
|
0.00%
0/57 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/37 • 1st dose to 30 days following last administration of study treatment
|
10.0%
1/10 • Number of events 1 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
Other adverse events
| Measure |
Total Run-In
n=57 participants at risk
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Run-In - Not Randomized
n=37 participants at risk
20 mg tasimelteon capsules
tasimelteon: 20 mg capsules, daily
|
Tasimelteon
n=10 participants at risk
20 mg tasimelteon capsules
tasimelteon: 20 mg tasimelteon capsules, daily
|
Placebo
n=10 participants at risk
Placebo capsules
Placebo: Placebo capsules, daily
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
7.0%
4/57 • Number of events 4 • 1st dose to 30 days following last administration of study treatment
|
5.4%
2/37 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Investigations
Blood creatine phosphokinase
|
5.3%
3/57 • Number of events 3 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/37 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Investigations
Alanine aminotransferase
|
3.5%
2/57 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/37 • 1st dose to 30 days following last administration of study treatment
|
10.0%
1/10 • Number of events 1 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Investigations
Crystal urine present
|
3.5%
2/57 • Number of events 3 • 1st dose to 30 days following last administration of study treatment
|
5.4%
2/37 • Number of events 3 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Investigations
Protein urine present
|
3.5%
2/57 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
5.4%
2/37 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Nervous system disorders
Headache
|
3.5%
2/57 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
2.7%
1/37 • Number of events 1 • 1st dose to 30 days following last administration of study treatment
|
10.0%
1/10 • Number of events 1 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Nervous system disorders
Somnolence
|
0.00%
0/57 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/37 • 1st dose to 30 days following last administration of study treatment
|
20.0%
2/10 • Number of events 3 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.5%
2/57 • Number of events 4 • 1st dose to 30 days following last administration of study treatment
|
5.4%
2/37 • Number of events 4 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
0.00%
0/57 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/37 • 1st dose to 30 days following last administration of study treatment
|
20.0%
2/10 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Gastrointestinal disorders
Constipation
|
3.5%
2/57 • Number of events 3 • 1st dose to 30 days following last administration of study treatment
|
5.4%
2/37 • Number of events 3 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
3.5%
2/57 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
5.4%
2/37 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Renal and urinary disorders
Urine abnormality
|
3.5%
2/57 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
5.4%
2/37 • Number of events 2 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/57 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/37 • 1st dose to 30 days following last administration of study treatment
|
20.0%
2/10 • Number of events 3 • 1st dose to 30 days following last administration of study treatment
|
0.00%
0/10 • 1st dose to 30 days following last administration of study treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place