Circadian Rhythm Sleep Disorders
Conditions
Brief summary
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.
Interventions
DRUGVEC-162
Sponsors
Vanda Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* No medical, psychiatric, or sleep disorders * Ability to provide written informed consent
Exclusion criteria
* Lifetime history of night shift work * Evidence of any sleep disorder * Psychiatric or neurological disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Circadian Phase Shift | Night 3 and Night 4 | 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. |
| Mean Sleep Efficiency | Night 4 and Night 2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | Night 2 and Night 4 | 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. |
| VEC-162 AUC | Night 4 | — |
| VEC-162 Cmax | Night 4 | — |
| VEC-162 Tmax | Night 4 | — |
Countries
United States
Participant flow
Pre-assignment details
Number of Enrolled Subjects = 45 Number of Enrollment Failures = 6
Participants by arm
| Arm | Count |
|---|---|
| Placebo Randomized to Placebo | 8 |
| 10 mg VEC-162 Randomized to 10 mg VEC-162 | 9 |
| 20 mg VEC-162 Randomized to 20 mg VEC-162 | 8 |
| 50 mg VEC-162 Randomized to 50 mg VEC-162 | 7 |
| 100 mg VEC-162 Randomized to 100 mg VEC-162 | 7 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | 10 mg VEC-162 | 20 mg VEC-162 | 50 mg VEC-162 | 100 mg VEC-162 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 27.5 years STANDARD_DEVIATION 6.7 | 31.8 years STANDARD_DEVIATION 7.4 | 32.5 years STANDARD_DEVIATION 9.6 | 27.4 years STANDARD_DEVIATION 6.2 | 30.4 years STANDARD_DEVIATION 9.5 | 30.0 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 4 Participants | 3 Participants | 3 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 8 / 9 | 7 / 8 | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 9 | 0 / 8 | 0 / 7 | 0 / 7 |
Outcome results
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.
Time frame: Night 3 and Night 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Circadian Phase Shift | -0.48 Hours | Standard Deviation 0.84 |
| 10 mg VEC-162 | Circadian Phase Shift | 0.18 Hours | Standard Deviation 2.48 |
| 20 mg VEC-162 | Circadian Phase Shift | -1.14 Hours | Standard Deviation 0.46 |
| 50 mg VEC-162 | Circadian Phase Shift | -0.50 Hours | Standard Deviation 0.32 |
| 100 mg VEC-162 | Circadian Phase Shift | -2.74 Hours | Standard Deviation 1.95 |
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.
Time frame: Night 4 and Night 2
Population: \*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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Sleep Efficiency | Full Night (% points) | -20.27 % points | Standard Deviation 18.72 |
| Placebo | Mean Sleep Efficiency | 1st Third of the Night (% points) | -12.30 % points | Standard Deviation 14.51 |
| Placebo | Mean Sleep Efficiency | 2nd Third of the Night (% points) | -34.92 % points | Standard Deviation 38.23 |
| Placebo | Mean Sleep Efficiency | 3rd Third of the NIght (% points) | -8.06 % points | Standard Deviation 29.69 |
| 10 mg VEC-162 | Mean Sleep Efficiency | Full Night (% points) | -7.77 % points | Standard Deviation 14.98 |
| 10 mg VEC-162 | Mean Sleep Efficiency | 3rd Third of the NIght (% points) | -10.51 % points | Standard Deviation 35.17 |
| 10 mg VEC-162 | Mean Sleep Efficiency | 1st Third of the Night (% points) | -0.47 % points | Standard Deviation 12.39 |
| 10 mg VEC-162 | Mean Sleep Efficiency | 2nd Third of the Night (% points) | -12.64 % points | Standard Deviation 13.83 |
| 20 mg VEC-162 | Mean Sleep Efficiency | 3rd Third of the NIght (% points) | -7.09 % points | Standard Deviation 26.24 |
| 20 mg VEC-162 | Mean Sleep Efficiency | 1st Third of the Night (% points) | -7.81 % points | Standard Deviation 14.52 |
| 20 mg VEC-162 | Mean Sleep Efficiency | 2nd Third of the Night (% points) | -5.11 % points | Standard Deviation 12.78 |
| 20 mg VEC-162 | Mean Sleep Efficiency | Full Night (% points) | -6.68 % points | Standard Deviation 12.69 |
| 50 mg VEC-162 | Mean Sleep Efficiency | Full Night (% points) | -5.87 % points | Standard Deviation 9.89 |
| 50 mg VEC-162 | Mean Sleep Efficiency | 1st Third of the Night (% points) | 0.95 % points | Standard Deviation 7.79 |
| 50 mg VEC-162 | Mean Sleep Efficiency | 3rd Third of the NIght (% points) | -16.48 % points | Standard Deviation 26.25 |
| 50 mg VEC-162 | Mean Sleep Efficiency | 2nd Third of the Night (% points) | -2.10 % points | Standard Deviation 4.14 |
| 100 mg VEC-162 | Mean Sleep Efficiency | 3rd Third of the NIght (% points) | 1.80 % points | Standard Deviation 14.15 |
| 100 mg VEC-162 | Mean Sleep Efficiency | 2nd Third of the Night (% points) | -2.30 % points | Standard Deviation 5.72 |
| 100 mg VEC-162 | Mean Sleep Efficiency | 1st Third of the Night (% points) | -5.63 % points | Standard Deviation 17.71 |
| 100 mg VEC-162 | Mean Sleep Efficiency | Full Night (% points) | -2.02 % points | Standard Deviation 4.94 |
Secondary
VEC-162 AUC
Time frame: Night 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | VEC-162 AUC | 171.73 ng*hr/mL | Standard Deviation 118.51 |
| 10 mg VEC-162 | VEC-162 AUC | 482.00 ng*hr/mL | Standard Deviation 329.48 |
| 20 mg VEC-162 | VEC-162 AUC | 614.34 ng*hr/mL | Standard Deviation 488.08 |
| 50 mg VEC-162 | VEC-162 AUC | 1916.06 ng*hr/mL | Standard Deviation 601.35 |
Secondary
VEC-162 Cmax
Time frame: Night 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | VEC-162 Cmax | 59.10 ng/mL | Standard Deviation 39.22 |
| 10 mg VEC-162 | VEC-162 Cmax | 139.94 ng/mL | Standard Deviation 116.1 |
| 20 mg VEC-162 | VEC-162 Cmax | 166.01 ng/mL | Standard Deviation 164.94 |
| 50 mg VEC-162 | VEC-162 Cmax | 417.80 ng/mL | Standard Deviation 187.19 |
Secondary
VEC-162 Tmax
Time frame: Night 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | VEC-162 Tmax | 1.90 hour | Standard Deviation 1.78 |
| 10 mg VEC-162 | VEC-162 Tmax | 2.04 hour | Standard Deviation 0.9 |
| 20 mg VEC-162 | VEC-162 Tmax | 2.42 hour | Standard Deviation 0.59 |
| 50 mg VEC-162 | VEC-162 Tmax | 3.03 hour | Standard Deviation 1.5 |
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.
Time frame: Night 2 and Night 4
Population: \*Placebo N = 7 and 100 mg VEC-162 N = 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | Latency to Persistent Sleep | 15.13 minutes | Standard Deviation 21.25 |
| Placebo | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | WASO* | 77.00 minutes | Standard Deviation 91.01 |
| 10 mg VEC-162 | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | Latency to Persistent Sleep | -8.25 minutes | Standard Deviation 16.34 |
| 10 mg VEC-162 | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | WASO* | 40.56 minutes | Standard Deviation 67.53 |
| 20 mg VEC-162 | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | Latency to Persistent Sleep | 5.00 minutes | Standard Deviation 11.89 |
| 20 mg VEC-162 | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | WASO* | 31.19 minutes | Standard Deviation 53.8 |
| 50 mg VEC-162 | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | WASO* | 31.21 minutes | Standard Deviation 52.69 |
| 50 mg VEC-162 | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | Latency to Persistent Sleep | -3.71 minutes | Standard Deviation 10.97 |
| 100 mg VEC-162 | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | Latency to Persistent Sleep | -4.17 minutes | Standard Deviation 6.93 |
| 100 mg VEC-162 | Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) | WASO* | 8.50 minutes | Standard Deviation 20.39 |