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The purpose of this study is to assess the safety and efficacy of VEC-162 compared to matching placebo on circadian phase shift and sleep parameters.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VEC-162 | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Circadian Phase Shift | Exposure response to VEC-162 on induction of circadian phase shift as measured by Dim Light Melatonin Onset (DLMO) was defined as the time change between Night 3 and Night 4 when melatonin production reached 25% of the maximum melatonin concentration. Samples below LOQ of the melatonin assay were assigned 5 pg/ml. | Night 3 and Night 4 |
| Mean Sleep Efficiency | Exposure response was measured by comparing the change in sleep efficiencies of VEC-162 and placebo treated subjects upon a sleep schedule phase advance. Sleep efficiency (total time asleep divided by the time allowed as an opportunity for sleep in a period multiplied by 100%, where time allowed for sleep was 8 hours or 480 minutes) was measured objectively by overnight polysomnographic recordings. Sleep efficiency was also compared in parts of the night by dividing the full night into thirds. | Night 4 and Night 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | Wake After Sleep Onset is defined as the total time that is scored as awake in a PSG occurring between sleep onset and lights-on prompt. Latency to Persistent Sleep is defined as the number of epochs (one 30-second interval of the sleep episode) from the beginning of the recording (lights-out) to the start of persistent sleep (first 20 consecutive non-wake state) divided by 2. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marlene Dressman, PhD | Vanda Pharmaceuticals Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanda Investigational Site | Boston | Massachusetts | United States | |||
| Vanda Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19054552 | Derived | Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB. Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials. Lancet. 2009 Feb 7;373(9662):482-91. doi: 10.1016/S0140-6736(08)61812-7. Epub 2008 Dec 4. |
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Number of Enrolled Subjects = 45 Number of Enrollment Failures = 6
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Randomized to Placebo |
| FG001 | 10 mg VEC-162 | Randomized to 10 mg VEC-162 |
| FG002 | 20 mg VEC-162 | Randomized to 20 mg VEC-162 |
| FG003 | 50 mg VEC-162 | Randomized to 50 mg VEC-162 |
| FG004 | 100 mg VEC-162 | Randomized to 100 mg VEC-162 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Randomized to Placebo |
| BG001 | 10 mg VEC-162 | Randomized to 10 mg VEC-162 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Circadian Phase Shift | Exposure response to VEC-162 on induction of circadian phase shift as measured by Dim Light Melatonin Onset (DLMO) was defined as the time change between Night 3 and Night 4 when melatonin production reached 25% of the maximum melatonin concentration. Samples below LOQ of the melatonin assay were assigned 5 pg/ml. | Posted | Mean | Standard Deviation | Hours | Night 3 and Night 4 |
|
1st dose to 30 days following last administration of study treatment
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Randomized to Placebo |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (7.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marlene Dressman, Ph.D. | Vanda Pharmaceuticals Inc. | 202-734-3462 | marelene.dressman@vandapharma.com |
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| ID | Term |
|---|---|
| D020178 | Sleep Disorders, Circadian Rhythm |
| ID | Term |
|---|---|
| D021081 | Chronobiology Disorders |
| D009422 | Nervous System Diseases |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
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| Night 2 and Night 4 |
| VEC-162 AUC | Night 4 |
| VEC-162 Cmax | Night 4 |
| VEC-162 Tmax | Night 4 |
| Detroit |
| Michigan |
| United States |
| BG002 |
| 20 mg VEC-162 |
Randomized to 20 mg VEC-162 |
| BG003 | 50 mg VEC-162 | Randomized to 50 mg VEC-162 |
| BG004 | 100 mg VEC-162 | Randomized to 100 mg VEC-162 |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Randomized to 20 mg VEC-162 |
| OG003 | 50 mg VEC-162 | Randomized to 50 mg VEC-162 |
| OG004 | 100 mg VEC-162 | Randomized to 100 mg VEC-162 |
|
|
| Primary | Mean Sleep Efficiency | Exposure response was measured by comparing the change in sleep efficiencies of VEC-162 and placebo treated subjects upon a sleep schedule phase advance. Sleep efficiency (total time asleep divided by the time allowed as an opportunity for sleep in a period multiplied by 100%, where time allowed for sleep was 8 hours or 480 minutes) was measured objectively by overnight polysomnographic recordings. Sleep efficiency was also compared in parts of the night by dividing the full night into thirds. | *N = 6 for 3rd Third of Night Efficiency and N=8 for 1st Third of Night Efficiency **N = 7 for 3rd Third of Night Efficiency | Posted | Mean | Standard Deviation | % points | Night 4 and Night 2 |
|
|
|
| Secondary | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | Wake After Sleep Onset is defined as the total time that is scored as awake in a PSG occurring between sleep onset and lights-on prompt. Latency to Persistent Sleep is defined as the number of epochs (one 30-second interval of the sleep episode) from the beginning of the recording (lights-out) to the start of persistent sleep (first 20 consecutive non-wake state) divided by 2. | *Placebo N = 7 and 100 mg VEC-162 N = 7 | Posted | Mean | Standard Deviation | minutes | Night 2 and Night 4 |
|
|
|
| Secondary | VEC-162 AUC | Posted | Mean | Standard Deviation | ng*hr/mL | Night 4 |
|
|
|
| Secondary | VEC-162 Cmax | Posted | Mean | Standard Deviation | ng/mL | Night 4 |
|
|
|
| Secondary | VEC-162 Tmax | Posted | Mean | Standard Deviation | hour | Night 4 |
|
|
|
| 0 |
| 8 |
| 8 |
| 8 |
| EG001 | 10 mg VEC-162 | Randomized to 10 mg VEC-162 | 0 | 9 | 8 | 9 |
| EG002 | 20 mg VEC-162 | Randomized to 20 mg VEC-162 | 0 | 8 | 7 | 8 |
| EG003 | 50 mg VEC-162 | Randomized to 50 mg VEC-162 | 0 | 7 | 7 | 7 |
| EG004 | 100 mg VEC-162 | Randomized to 100 mg VEC-162 | 0 | 7 | 7 | 7 |
| Eosinophilia | Blood and lymphatic system disorders | MedDRA (7.0) | Systematic Assessment |
|
| Conjunctival Hyperaemia | Eye disorders | MedDRA (7.0) | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | MedDRA (7.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (7.0) | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (7.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (7.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (7.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (7.0) | Systematic Assessment |
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| Abdominal Tenderness | Gastrointestinal disorders | MedDRA (7.0) | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA (7.0) | Systematic Assessment |
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| Application Site Irritation | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Injection Site Pain | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Injection Site Bruising | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Application Site Pain | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Feeling Hot | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Application Site Reaction | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Asthenia | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Chest Pain | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Injection Site Anaesthesia | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Injection Site Burning | General disorders | MedDRA (7.0) | Systematic Assessment |
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| Injection Site Discomfort | General disorders | MedDRA (7.0) | Systematic Assessment |
|
| Injection Site Erythema | General disorders | MedDRA (7.0) | Systematic Assessment |
|
| Injection Site Irritation | General disorders | MedDRA (7.0) | Systematic Assessment |
|
| Injection Site Movement Impairment | General disorders | MedDRA (7.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (7.0) | Systematic Assessment |
|
| Herpes Simplex | Infections and infestations | MedDRA (7.0) | Systematic Assessment |
|
| Haematocrit Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Haemoglobin Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Blood Pressure Systolic Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| White Blood Cell Count Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Blood Pressure Diastolic Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Blood Pressure Diastolic Increased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Neutrophil Count Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Alanine Aminotransferase Increased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Blood Phosphorus Increased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Blood Potassium Increased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Blood Pressure Systolic Increased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Electrocardiogram Abnormal | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Eosinophil Count Increased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Heart Rate Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Heart Rate Increased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Lymphocyte Count Increased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Monocyte Count Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Platelet Count Decreased | Investigations | MedDRA (7.0) | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (7.0) | Systematic Assessment |
|
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA (7.0) | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (7.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (7.0) | Systematic Assessment |
|
| Musculoskeletal Stiffness | Musculoskeletal and connective tissue disorders | MedDRA (7.0) | Systematic Assessment |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA (7.0) | Systematic Assessment |
|
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA (7.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (7.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (7.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (7.0) | Systematic Assessment |
|
| Syncope Vasovagal | Nervous system disorders | MedDRA (7.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (7.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (7.0) | Systematic Assessment |
|
| Nervousness | Psychiatric disorders | MedDRA (7.0) | Systematic Assessment |
|
| Abnormal Dreams | Psychiatric disorders | MedDRA (7.0) | Systematic Assessment |
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| Mental Disorder | Psychiatric disorders | MedDRA (7.0) | Systematic Assessment |
|
| Sleep Disorder | Psychiatric disorders | MedDRA (7.0) | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA (7.0) | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (7.0) | Systematic Assessment |
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| Vaginal Discharge | Reproductive system and breast disorders | MedDRA (7.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (7.0) | Systematic Assessment |
|
| Pharyngolaryngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (7.0) | Systematic Assessment |
|
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (7.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (7.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (7.0) | Systematic Assessment |
|
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| D009784 |
| Occupational Diseases |
| D001523 | Mental Disorders |
| 1st Third of the Night (% points) |
|
| 2nd Third of the Night (% points) |
|
| 3rd Third of the NIght (% points) |
|
| WASO* |
|