Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 τ 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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tasimelteon | Experimental | 20 mg tasimelteon capsules, PO daily for 6 months |
|
| placebo | Placebo Comparator | Placebo capsules, PO daily for 6 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tasimelteon | Drug | 20 mg tasimelteon capsules, PO daily for 6 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Entrained as Assessed by Urinary aMT6 | 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 48 hour periods , collected approximately 1 week apart for 4 separate weeks, during the screening and month 1 of the randomization phase of the trial. Entrainment was defined as having a post-baseline τ value less than 24.1 and a 95% CI that included 24.0. | 1 month |
| Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 3 on N24CRS | Clinical response is defined as the coincident demonstration of entrainment (aMT6) and a score ≥ 3 on the Non-24 Clinical Response Scale (N24CRS). N24CRS measures improvement in sleep-wake measures and overall functioning (LQ-nTST, UQ-dTSD, MoST and CGI-C). Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: >45 minutes increase in average nighttime sleep duration; UQ-dTSD: >45 minutes decrease in average daytime sleep duration; MoST: >30 minutes increase and a standard deviation <2 hours during double-masked phase (6 months); CGI-C: <2.0 from the average of D112 and Day 183 compared to baseline For patients randomized to tasimelteon 20 mg and who also participated in the screening phase of Study 3203 (month 7 of treatment), the screening τ from Study 3203 was used if the patient did not become entrained in Study 3201 but did become entrained during the screening phase of Study 3203. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Entrained as Assessed by Urinary Cortisol | 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 48 hour periods, approximately 1 week apart for 4 separate weeks, during the screening and month 1 of the randomization phase of the trial. Entrainment was defined as having a post-baseline τ value less than 24.1 and a 95% CI that included 24.0. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 2 on N24CRS | Clinical response is defined as the coincident demonstration of entrainment (aMT6) and a score ≥ 2 on the Non-24 Clinical Response Scale (N24CRS) which includes LQ-nTST, UQ-dTSD, MoST and CGI-C assessments. Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: >45 minutes increase in average nighttime sleep duration; UQ-dTSD: >45 minutes decrease in average daytime sleep duration; MoST: >30 minutes increase and a standard deviation <2 hours during double-masked phase (6 months); CGI-C: <2.0 from the average of D112 and Day 183 compared to baseline For patients randomized to tasimelteon 20 mg and who also participated in the screening phase of Study 3203 (month 7 of treatment), the screening τ from Study 3203 was used if the patient did not become entrained in Study 3201 but did become entrained during the screening phase of Study 3203. |
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:
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:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Vanda Pharmaceuticals | Vanda Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pulmonary Associates, PA | Phoenix | Arizona | 85006 | United States | ||
| SDS Clinical Trials Inc. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26466871 | Derived | Lockley SW, Dressman MA, Licamele L, Xiao C, Fisher DM, Flynn-Evans EE, Hull JT, Torres R, Lavedan C, Polymeropoulos MH. Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials. Lancet. 2015 Oct 31;386(10005):1754-64. doi: 10.1016/S0140-6736(15)60031-9. Epub 2015 Aug 4. |
Not provided
Not provided
Not provided
*Various category for the Randomization Phase: 4 patients in each treatment group discontinued due to study termination by the sponsor and 1 patient in the tasimelteon group discontinued due to travel across multiple time zones
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Tasimelteon (Randomized) | 20 mg tasimelteon capsules, PO daily for 6 months tasimelteon: 20 mg tasimelteon capsules, PO daily for 6 months |
| FG001 | Placebo (Randomized) | Placebo capsules, PO daily for 6 months Placebo: Placebo capsules, PO daily for 6 months |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Randomization Phase |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo capsules, PO daily for 6 months |
|
| 1 month |
| Average Clinical Global Impression of Change (CGI-C) | CGI-C scores range from 1 (very much improved) to 7 (very much worse). The average post-randomization score was obtained for each patient by averaging the last 2 scheduled assessments (Day D112 and Day D183). Lower number indicates improvement. | Day 112 and 183 |
| Proportion of Responders With a Combined Sleep/Wake Response for LQ-nTST (≥ 90 Minutes) and UQ-dTSD (≤ 90 Minutes) | The sleep/wake response represents measurement of the combined improvement in the nighttime sleep duration and daytime sleep duration. Individuals that have an improvement in nighttime sleep and daytime sleep, defined as an increase of 90 minutes or more in the lower quartile of subjective nighttime total sleep time (LQ-nTST) and a decrease of 90 minutes or more in the upper quartile of daytime total sleep duration (UQ-dTSD) are considered to be a responder. | 6 months |
| Average Lower Quartile of Nights of Nighttime Total Sleep Time (LQ-nTST) | LQ-nTST measures the difference in average nighttime sleep during the patient's worst 25% of nights (shortest total nighttime sleep) between the randomized phase (6 months)and the screening phase (~ 6 weeks). The higher number indicates improvement. | 6 months |
| Average Upper Quartile of Days of Subjective Daytime Sleep Duration (UQ-dTSD) | UQ-dTSD measures the difference in average daytime sleep during the patient's worst 25% of days (longest total daytime sleep) between the randomized phase (6 months) and the screening phase (~ 6 weeks). Lower number indicates improvement. | 6 months |
| Average Midpoint of Sleep (MoST) | Midpoint of Sleep Timing (MoST) is the measurement of the average midpoint of sleep time 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. | 6 months |
| Number of Patients With a Treatment Emergent Adverse Event (Open Label Extension Phase Only) | Adverse events were recorded in the source documents from the time of the patient's informed consent signature until the end of the patient's study participation. An AE was defined as any untoward medical occurrence in a clinical investigation patient who does not necessarily have causal relationship with treatment. | 6 months |
| 6 months |
| Proportion of Patients With a Clinical Response (Score of ≥ 3 on N24CRS) | Non-24 Clinical Response Scale (N24CRS) was a 4-item scale which includes LQ-nTST, UQ-dTSD, MoST and CGI-C assessments. Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: >45 minutes increase in average nighttime sleep duration; UQ-dTSD: >45 minutes decrease in average daytime sleep duration; MoST: >30 minutes increase and a standard deviation <2 hours during double-masked phase (6 months); CGI-C: <2.0 from the average of D112 and Day 183 compared to baseline | 6 months |
| Proportion of Patients With a Clinical Response (Score of ≥ 2 on N24CRS) | Non-24 Clinical Response Scale (N24CRS) was a 4-item scale which includes LQ-nTST, UQ-dTSD, MoST and CGI-C assessments. Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: >45 minutes increase in average nighttime sleep duration; UQ-dTSD: >45 minutes decrease in average daytime sleep duration; MoST: >30 minutes increase and a standard deviation <2 hours during double-masked phase (6 months); CGI-C: <2.0 from the average of D112 and Day 183 compared to baseline | 6 months |
| Orange |
| California |
| 92868 |
| United States |
| VA Palo Alto Health Care System/PAIRE (San Fransisco Bay Area) | Palo Alto | California | 94304 | United States |
| St. Johns Sleep Disorder Center - St. Johns Medical Plaza | Santa Monica | California | 90404 | United States |
| Radiant Research - Denver | Denver | Colorado | 80239 | United States |
| PAB Clinical Research Inc. | Brandon | Florida | 33511 | United States |
| Kendall South Medical Center, Inc. | Miami | Florida | 33175 | United States |
| Ocean Sleep Disorders Center - Ormond Beach | Ormond Beach | Florida | 32174 | United States |
| Sleep Disorders Center Of Georgia | Atlanta | Georgia | 30342 | United States |
| Suburban Lung Associates SC (Chicago Metropolitan Area) | Elk Grove Village | Illinois | 60007 | United States |
| The Center for Sleep and Wake Disorders (Washington, D.C. Metropolitan Area) | Chevy Chase | Maryland | 20815 | United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| Michigan Head-Pain Neurological Institute | Ann Arbor | Michigan | 48104 | United States |
| St. Luke's Sleep Medicine and Research Center (St. Louis Metropolitan Area) | Chesterfield | Missouri | 63017 | United States |
| New York Eye and Ear Infirmary | New York | New York | 10003 | United States |
| Tri-State Sleep Disorders Center | Cincinnati | Ohio | 45246 | United States |
| Ohio Sleep Medicine Institute (Columbus Metropolitan Area) | Dublin | Ohio | 43017 | United States |
| Lynn Health Science Institute | Oklahoma City | Oklahoma | 73112 | United States |
| Columbia Research Group Inc. | Portland | Oregon | 97239 | United States |
| Center For Sleep Medicine at Chestnut Hill Hospital | Philadelphia | Pennsylvania | 19118 | United States |
| Consolidated Clinical trials | Pittsburgh | Pennsylvania | 15221 | United States |
| SleepMed, Inc. - Columbia | Columbia | South Carolina | 29201 | United States |
| Todd J. Swick, M.D., P.A. | Houston | Texas | 77063 | United States |
| Advanced Sleep Research GmbH | Berlin | 10117 | Germany |
| Bergmannsheil University Hospital - Medical Clinic III | Bochum | 44789 | Germany |
| Klinische-Forschung Hannover Mitte | Hanover | 30159 | Germany |
| Universitaetsklinikum Glesen and Marburg gmbH/Schlaflabor - Sleep Lab University Marburg | Marburg | 35043 | Germany |
| Bonomed Studiezentrum | Munich | 80331 | Germany |
| FG002 | Open Label Tasimelteon | 20 mg tasimelteon capsules, PO daily for 6 months tasimelteon: 20 mg tasimelteon capsules, PO daily for 6 months |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Open Label Extension Phase |
|
|
52 patients entered the OLE Phase from screening and 3 patients rolled over after completing the Randomization Phase (2:tasimelteon; 1:placebo). For this analysis, 3 patients are included in the randomized arms and not the OLE. A separate analysis has been done for both age and gender for the 3 subjects (Rand to OLE).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tasimelteon (Randomized) | 20 mg tasimelteon capsules, PO daily for 6 months tasimelteon: 20 mg tasimelteon capsules, PO daily for 6 months |
| BG001 | Placebo (Randomized) | Placebo capsules, PO daily for 6 months Placebo: Placebo capsules, PO daily for 6 months |
| BG002 | Open Label Tasimelteon | 20 mg tasimelteon capsules, PO daily for 6 months tasimelteon: 20 mg tasimelteon capsules, PO daily for 6 months |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | N = 2 (tasimelteon randomized then went to OLE) and 1 (placebo randomized then went to OLE) | Mean | Standard Deviation | years |
| ||||||||||||||
| Sex/Gender, Customized | N = 2 (tasimelteon randomized then went to OLE) and 1 (placebo randomized then went to OLE) | Number | participants |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Patients Entrained as Assessed by Urinary aMT6 | 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 48 hour periods , collected approximately 1 week apart for 4 separate weeks, during the screening and month 1 of the randomization phase of the trial. Entrainment was defined as having a post-baseline τ value less than 24.1 and a 95% CI that included 24.0. | Intent-to-Treat (ITT) Population: all subjects randomized into the study that have τ calculated post-randomization. | Posted | Number | percentage of patients | 1 month |
|
|
| |||||||||||||||||||||||||||||
| Primary | Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 3 on N24CRS | Clinical response is defined as the coincident demonstration of entrainment (aMT6) and a score ≥ 3 on the Non-24 Clinical Response Scale (N24CRS). N24CRS measures improvement in sleep-wake measures and overall functioning (LQ-nTST, UQ-dTSD, MoST and CGI-C). Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: >45 minutes increase in average nighttime sleep duration; UQ-dTSD: >45 minutes decrease in average daytime sleep duration; MoST: >30 minutes increase and a standard deviation <2 hours during double-masked phase (6 months); CGI-C: <2.0 from the average of D112 and Day 183 compared to baseline For patients randomized to tasimelteon 20 mg and who also participated in the screening phase of Study 3203 (month 7 of treatment), the screening τ from Study 3203 was used if the patient did not become entrained in Study 3201 but did become entrained during the screening phase of Study 3203. | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Number | percentage of patients | 6 months |
| |||||||||||||||||||||||||||||||
| Other Pre-specified | Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 2 on N24CRS | Clinical response is defined as the coincident demonstration of entrainment (aMT6) and a score ≥ 2 on the Non-24 Clinical Response Scale (N24CRS) which includes LQ-nTST, UQ-dTSD, MoST and CGI-C assessments. Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: >45 minutes increase in average nighttime sleep duration; UQ-dTSD: >45 minutes decrease in average daytime sleep duration; MoST: >30 minutes increase and a standard deviation <2 hours during double-masked phase (6 months); CGI-C: <2.0 from the average of D112 and Day 183 compared to baseline For patients randomized to tasimelteon 20 mg and who also participated in the screening phase of Study 3203 (month 7 of treatment), the screening τ from Study 3203 was used if the patient did not become entrained in Study 3201 but did become entrained during the screening phase of Study 3203. | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Number | percentage of patients | 6 months |
| |||||||||||||||||||||||||||||||
| Other Pre-specified | Proportion of Patients With a Clinical Response (Score of ≥ 3 on N24CRS) | Non-24 Clinical Response Scale (N24CRS) was a 4-item scale which includes LQ-nTST, UQ-dTSD, MoST and CGI-C assessments. Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: >45 minutes increase in average nighttime sleep duration; UQ-dTSD: >45 minutes decrease in average daytime sleep duration; MoST: >30 minutes increase and a standard deviation <2 hours during double-masked phase (6 months); CGI-C: <2.0 from the average of D112 and Day 183 compared to baseline | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Number | percentage of patients | 6 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Proportion of Patients Entrained as Assessed by Urinary Cortisol | 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 48 hour periods, approximately 1 week apart for 4 separate weeks, during the screening and month 1 of the randomization phase of the trial. Entrainment was defined as having a post-baseline τ value less than 24.1 and a 95% CI that included 24.0. | Intent-to-Treat (ITT) Population: all subjects randomized into the study that have τ calculated post-randomization. | Posted | Number | percentage of patients | 1 month |
|
| ||||||||||||||||||||||||||||||
| Secondary | Average Clinical Global Impression of Change (CGI-C) | CGI-C scores range from 1 (very much improved) to 7 (very much worse). The average post-randomization score was obtained for each patient by averaging the last 2 scheduled assessments (Day D112 and Day D183). Lower number indicates improvement. | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Mean | Standard Error | score | Day 112 and 183 |
|
| |||||||||||||||||||||||||||||
| Secondary | Proportion of Responders With a Combined Sleep/Wake Response for LQ-nTST (≥ 90 Minutes) and UQ-dTSD (≤ 90 Minutes) | The sleep/wake response represents measurement of the combined improvement in the nighttime sleep duration and daytime sleep duration. Individuals that have an improvement in nighttime sleep and daytime sleep, defined as an increase of 90 minutes or more in the lower quartile of subjective nighttime total sleep time (LQ-nTST) and a decrease of 90 minutes or more in the upper quartile of daytime total sleep duration (UQ-dTSD) are considered to be a responder. | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Number | percentage of patients | 6 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Average Lower Quartile of Nights of Nighttime Total Sleep Time (LQ-nTST) | LQ-nTST measures the difference in average nighttime sleep during the patient's worst 25% of nights (shortest total nighttime sleep) between the randomized phase (6 months)and the screening phase (~ 6 weeks). The higher number indicates improvement. | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Mean | Standard Error | minutes | 6 months |
|
| |||||||||||||||||||||||||||||
| Secondary | Average Upper Quartile of Days of Subjective Daytime Sleep Duration (UQ-dTSD) | UQ-dTSD measures the difference in average daytime sleep during the patient's worst 25% of days (longest total daytime sleep) between the randomized phase (6 months) and the screening phase (~ 6 weeks). Lower number indicates improvement. | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Mean | Standard Error | minutes | 6 months |
|
| |||||||||||||||||||||||||||||
| Secondary | Average Midpoint of Sleep (MoST) | Midpoint of Sleep Timing (MoST) is the measurement of the average midpoint of sleep time 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. | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Mean | Standard Error | minutes | 6 months |
|
| |||||||||||||||||||||||||||||
| Post-Hoc | Proportion of Responders With a Combined Sleep/Wake Response for LQ-nTST (≥ 45 Minutes) and UQ-dTSD (≤ 45 Minutes) | Responder analysis with responder defined as an increase of 45 minutes or more in (LQ-nTST) and a decrease of 45 minutes or more in (UQ-dTSD). | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Number | percentage of patients | 6 months |
|
| ||||||||||||||||||||||||||||||
| Other Pre-specified | Proportion of Patients With a Clinical Response (Score of ≥ 2 on N24CRS) | Non-24 Clinical Response Scale (N24CRS) was a 4-item scale which includes LQ-nTST, UQ-dTSD, MoST and CGI-C assessments. Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: >45 minutes increase in average nighttime sleep duration; UQ-dTSD: >45 minutes decrease in average daytime sleep duration; MoST: >30 minutes increase and a standard deviation <2 hours during double-masked phase (6 months); CGI-C: <2.0 from the average of D112 and Day 183 compared to baseline | Analysis Population: all patients in the ITT population that had at least 70% of 1 circadian cycle of nighttime total sleep data reported during each phase (screening and post-randomization) | Posted | Number | percentage of patients | 6 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Patients With a Treatment Emergent Adverse Event (Open Label Extension Phase Only) | Adverse events were recorded in the source documents from the time of the patient's informed consent signature until the end of the patient's study participation. An AE was defined as any untoward medical occurrence in a clinical investigation patient who does not necessarily have causal relationship with treatment. | One subject who rolled into the OLE from the randomized phase (tasimelteon) experienced an unrelated TEAE during the OLE phase. | Posted | Number | participants | 6 months |
|
|
1st dose to 30 days following last administration of study treatment
55 subjects enrolled into the Open Label phase (including 3 randomized subjects who rolled into the OLE). One subject enrolled in the Open Label phase but did not take any study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tasimelteon (Randomized) | 20 mg tasimelteon capsules, PO daily for 6 months tasimelteon: 20 mg tasimelteon capsules, PO daily for 6 months | 4 | 42 | 20 | 42 | ||
| EG001 | Placebo (Randomized) | Placebo capsules, PO daily for 6 months Placebo: Placebo capsules, PO daily for 6 months | 2 | 42 | 13 | 42 | ||
| EG002 | Open Label Tasimelteon | 20 mg tasimelteon capsules, PO daily for 6 months tasimelteon: 20 mg tasimelteon capsules, PO daily for 6 months | 2 | 54 | 21 | 54 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Procedural Pain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
| |
| Small Intestinal Obstruction | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Acute Lymphocytic Leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Serotonin Syndrome | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Transient Ischaemic Attack | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Asparate aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Abnormal dreams | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marlene Dressman, Ph.D. | Vanda Pharmaceuticals Inc. | 202-734-3462 | marlene.dressman@vandapharma.com |
| ID | Term |
|---|---|
| D020178 | Sleep Disorders, Circadian Rhythm |
| D001766 | Blindness |
| D005128 | Eye Diseases |
| D021081 | Chronobiology Disorders |
| D012893 | Sleep Wake Disorders |
| D020920 | Dyssomnias |
| D009422 | Nervous System Diseases |
| ID | Term |
|---|---|
| D009784 | Occupational Diseases |
| D001523 | Mental Disorders |
| D014786 | Vision Disorders |
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C478745 | tasimelteon |
Not provided
Not provided
Not provided
| Protocol Violation |
|
| Study Termination |
|
| Unsatisfactory Therapeutic Effect |
|
| Rand to OLE (Male) |
|
| Male |
|
Placebo capsules, PO daily for 6 months
Placebo: Placebo capsules, PO daily for 6 months
|
|
|
|
| Participants |
|
|
|
|
| Participants |
|
|
|
|
|
|
| Participants |
|
|
|