Trial Outcomes & Findings for Safety and Efficacy of VEC-162 on Circadian Rhythm in Healthy Adult Volunteers (NCT NCT00490945)

Last Updated: 2014-08-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

Night 3 and Night 4

Results posted on

2014-08-26

Participant Flow

Number of Enrolled Subjects = 45 Number of Enrollment Failures = 6

Participant milestones

Participant milestones
Measure	Placebo Randomized to Placebo	10 mg VEC-162 Randomized to 10 mg VEC-162	20 mg VEC-162 Randomized to 20 mg VEC-162	50 mg VEC-162 Randomized to 50 mg VEC-162	100 mg VEC-162 Randomized to 100 mg VEC-162
Overall Study STARTED	8	9	8	7	7
Overall Study COMPLETED	8	8	8	7	7
Overall Study NOT COMPLETED	0	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Randomized to Placebo	10 mg VEC-162 Randomized to 10 mg VEC-162	20 mg VEC-162 Randomized to 20 mg VEC-162	50 mg VEC-162 Randomized to 50 mg VEC-162	100 mg VEC-162 Randomized to 100 mg VEC-162
Overall Study Adverse Event	0	1	0	0	0

Baseline Characteristics

Safety and Efficacy of VEC-162 on Circadian Rhythm in Healthy Adult Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=8 Participants Randomized to Placebo	10 mg VEC-162 n=9 Participants Randomized to 10 mg VEC-162	20 mg VEC-162 n=8 Participants Randomized to 20 mg VEC-162	50 mg VEC-162 n=7 Participants Randomized to 50 mg VEC-162	100 mg VEC-162 n=7 Participants Randomized to 100 mg VEC-162	Total n=39 Participants Total of all reporting groups
Age, Continuous	27.5 years STANDARD_DEVIATION 6.7 • n=5 Participants	31.8 years STANDARD_DEVIATION 7.4 • n=7 Participants	32.5 years STANDARD_DEVIATION 9.6 • n=5 Participants	27.4 years STANDARD_DEVIATION 6.2 • n=4 Participants	30.4 years STANDARD_DEVIATION 9.5 • n=21 Participants	30.0 years STANDARD_DEVIATION 7.9 • n=8 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	20 Participants n=8 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	19 Participants n=8 Participants

PRIMARY outcome

Timeframe: Night 3 and Night 4

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Randomized to Placebo	10 mg VEC-162 n=8 Participants Randomized to 10 mg VEC-162	20 mg VEC-162 n=7 Participants Randomized to 20 mg VEC-162	50 mg VEC-162 n=4 Participants Randomized to 50 mg VEC-162	100 mg VEC-162 n=5 Participants Randomized to 100 mg VEC-162
Circadian Phase Shift	-0.48 Hours Standard Deviation 0.84	0.18 Hours Standard Deviation 2.48	-1.14 Hours Standard Deviation 0.46	-0.50 Hours Standard Deviation 0.32	-2.74 Hours Standard Deviation 1.95

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants Randomized to Placebo	10 mg VEC-162 n=8 Participants Randomized to 10 mg VEC-162	20 mg VEC-162 n=8 Participants Randomized to 20 mg VEC-162	50 mg VEC-162 n=7 Participants Randomized to 50 mg VEC-162	100 mg VEC-162 n=7 Participants Randomized to 100 mg VEC-162
Mean Sleep Efficiency Full Night (% points)	-20.27 % points Standard Deviation 18.72	-7.77 % points Standard Deviation 14.98	-6.68 % points Standard Deviation 12.69	-5.87 % points Standard Deviation 9.89	-2.02 % points Standard Deviation 4.94
Mean Sleep Efficiency 1st Third of the Night (% points)	-12.30 % points Standard Deviation 14.51	-0.47 % points Standard Deviation 12.39	-7.81 % points Standard Deviation 14.52	0.95 % points Standard Deviation 7.79	-5.63 % points Standard Deviation 17.71
Mean Sleep Efficiency 2nd Third of the Night (% points)	-34.92 % points Standard Deviation 38.23	-12.64 % points Standard Deviation 13.83	-5.11 % points Standard Deviation 12.78	-2.10 % points Standard Deviation 4.14	-2.30 % points Standard Deviation 5.72
Mean Sleep Efficiency 3rd Third of the NIght (% points)	-8.06 % points Standard Deviation 29.69	-10.51 % points Standard Deviation 35.17	-7.09 % points Standard Deviation 26.24	-16.48 % points Standard Deviation 26.25	1.80 % points Standard Deviation 14.15

SECONDARY outcome

Timeframe: Night 2 and Night 4

Population: \*Placebo N = 7 and 100 mg VEC-162 N = 7

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.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Randomized to Placebo	10 mg VEC-162 n=8 Participants Randomized to 10 mg VEC-162	20 mg VEC-162 n=8 Participants Randomized to 20 mg VEC-162	50 mg VEC-162 n=7 Participants Randomized to 50 mg VEC-162	100 mg VEC-162 n=6 Participants Randomized to 100 mg VEC-162
Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) Latency to Persistent Sleep	15.13 minutes Standard Deviation 21.25	-8.25 minutes Standard Deviation 16.34	5.00 minutes Standard Deviation 11.89	-3.71 minutes Standard Deviation 10.97	-4.17 minutes Standard Deviation 6.93
Wake After Sleep Onset (WASO), and Latency to Persistent Sleep (LPS) WASO*	77.00 minutes Standard Deviation 91.01	40.56 minutes Standard Deviation 67.53	31.19 minutes Standard Deviation 53.80	31.21 minutes Standard Deviation 52.69	8.50 minutes Standard Deviation 20.39

SECONDARY outcome

Timeframe: Night 4

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Randomized to Placebo	10 mg VEC-162 n=8 Participants Randomized to 10 mg VEC-162	20 mg VEC-162 n=7 Participants Randomized to 20 mg VEC-162	50 mg VEC-162 n=7 Participants Randomized to 50 mg VEC-162	100 mg VEC-162 Randomized to 100 mg VEC-162
VEC-162 AUC	171.73 ng*hr/mL Standard Deviation 118.51	482.00 ng*hr/mL Standard Deviation 329.48	614.34 ng*hr/mL Standard Deviation 488.08	1916.06 ng*hr/mL Standard Deviation 601.35	—

SECONDARY outcome

Timeframe: Night 4

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Randomized to Placebo	10 mg VEC-162 n=8 Participants Randomized to 10 mg VEC-162	20 mg VEC-162 n=7 Participants Randomized to 20 mg VEC-162	50 mg VEC-162 n=7 Participants Randomized to 50 mg VEC-162	100 mg VEC-162 Randomized to 100 mg VEC-162
VEC-162 Cmax	59.10 ng/mL Standard Deviation 39.22	139.94 ng/mL Standard Deviation 116.10	166.01 ng/mL Standard Deviation 164.94	417.80 ng/mL Standard Deviation 187.19	—

SECONDARY outcome

Timeframe: Night 4