Trial Outcomes & Findings for A Study of LY2624803 in Japanese Participants With Transient Insomnia (NCT NCT01784614)
NCT ID: NCT01784614
Last Updated: 2016-01-28
Results Overview
WASO was calculated as total time in awake epochs between sleep onset time (first stage 2 epoch) and the end of the primary recording period (8 hours after lights -off). Data presented are Geometric Least Squares (LS) means. Geometric LS mean was calculated using mixed models analysis. The model included factors for treatment, treatment sequence, period and participants.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
8 hours in Periods 1, 2 and 3
Results posted on
2016-01-28
Participant Flow
This was a double-blind, randomized, placebo-controlled, 4-period cross-over study. The first 3 of which were used for polysomnography (PSG) measurements, and the fourth period was used to determine plasma concentrations of LY2624803 to estimate pharmacokinetic (PK) parameters.
Participant milestones
| Measure |
Cohort 1
Period 1: Single dose of 1 placebo capsule plus placebo solution administered orally.
Period 2: Single dose of one 1.0 milligram (mg) LY2624803 capsule plus placebo solution administered orally.
Period 3: Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 4: Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally.
There was at least 7 days washout between each period.
|
Cohort 2
Period 1: Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 2: Single dose of 1 placebo capsule plus placebo solution administered orally.
Period 3: Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 4: Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally.
There was at least 7 days washout between each period.
|
Cohort 3
Period 1: Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 2: Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 3: Single dose of 1 placebo capsule plus placebo solution administered orally.
Period 4: Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally.
There was at least 7 days washout between each period.
|
Cohort 4
Period 1: Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 2: Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 3: Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 4: Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally.
There was at least 7 days washout between each period.
|
Cohort 5
Period 1: Single dose of 1 placebo capsule plus placebo solution administered orally.
Period 2: Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 3: Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 4: Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally.
There was at least 7 days washout between each period.
|
Cohort 6
Period 1: Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 2: Single dose of 1 placebo capsule plus placebo solution administered orally.
Period 3: Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally.
Period 4: Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally.
There was at least 7 days washout between each period.
|
Cohort 7
Period 1: Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 2: Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally.
Period 3: Single dose of 1 placebo capsule plus placebo solution administered orally.
Period 4: Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally.
There was at least 7 days washout between each period.
|
Cohort 8
Period 1: Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally.
Period 2: Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 3: Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally.
Period 4: Single dose of 1.0 mg LY2624803 solution plus 1 placebo capsule administered orally.
There was at least 7 days washout between each period.
|
|---|---|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
3
|
3
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Period 1
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
3
|
2
|
|
Period 2
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
3
|
2
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
3
|
2
|
3
|
3
|
3
|
3
|
3
|
2
|
|
Period 3
COMPLETED
|
3
|
2
|
3
|
3
|
3
|
3
|
3
|
2
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
3
|
2
|
3
|
3
|
3
|
3
|
3
|
2
|
|
Period 4
COMPLETED
|
3
|
2
|
3
|
3
|
3
|
3
|
3
|
2
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of LY2624803 in Japanese Participants With Transient Insomnia
Baseline characteristics by cohort
| Measure |
Overall
n=24 Participants
Single dose of 0.1 mg LY2624803 oral solution plus 1 placebo capsule, one 1.0, 3.0 or 6.0 mg LY2624803 capsule plus placebo solution administered orally in up to 2 of 4 periods or 1 placebo capsule plus placebo solution administered orally in up to 1 of 4 periods.
There was at least 7 days washout between each period.
|
|---|---|
|
Age, Continuous
|
54.1 years
STANDARD_DEVIATION 14.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 hours in Periods 1, 2 and 3Population: All randomized participants who received at least 1 dose of study drug and had PSG measurements in Periods 1, 2 and 3.
WASO was calculated as total time in awake epochs between sleep onset time (first stage 2 epoch) and the end of the primary recording period (8 hours after lights -off). Data presented are Geometric Least Squares (LS) means. Geometric LS mean was calculated using mixed models analysis. The model included factors for treatment, treatment sequence, period and participants.
Outcome measures
| Measure |
0.1 mg LY2624803
n=8 Participants
Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally in Periods 1, 2 and 3.
|
1.0 mg LY2624803
n=17 Participants
Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
3.0 mg LY2624803
n=16 Participants
Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
6.0 mg LY2624803
n=8 Participants
Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
Placebo
n=17 Participants
Single dose of 1 placebo capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
|---|---|---|---|---|---|
|
Wake After Sleep Onset (WASO) With LY2624803 Compared to Placebo
|
58.88 minutes (min)
Interval 33.32 to 104.05
|
40.70 minutes (min)
Interval 25.67 to 64.54
|
32.27 minutes (min)
Interval 20.27 to 51.37
|
18.42 minutes (min)
Interval 10.44 to 32.51
|
61.10 minutes (min)
Interval 38.6 to 96.72
|
SECONDARY outcome
Timeframe: 8 hours in Periods 1, 2 and 3Population: All randomized participants who received at least 1 dose of study drug and had PSG measurements in Periods 1, 2 and 3.
LPS is defined as the latency from the lights-off time to the first stage 2 sleep followed by at least 10 consecutive minutes of sleep epochs. Data presented are Geometric LS means. Geometric LS mean was calculated using mixed models analysis. The model included factors for treatment, treatment sequence, period and participants.
Outcome measures
| Measure |
0.1 mg LY2624803
n=8 Participants
Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally in Periods 1, 2 and 3.
|
1.0 mg LY2624803
n=17 Participants
Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
3.0 mg LY2624803
n=16 Participants
Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
6.0 mg LY2624803
n=8 Participants
Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
Placebo
n=17 Participants
Single dose of 1 placebo capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
|---|---|---|---|---|---|
|
Latency to Persistent Sleep (LPS)
|
14.30 min
Interval 7.41 to 27.59
|
8.39 min
Interval 5.41 to 13.02
|
7.84 min
Interval 5.01 to 12.28
|
7.27 min
Interval 3.78 to 13.99
|
10.40 min
Interval 6.72 to 16.09
|
SECONDARY outcome
Timeframe: 8 hours in Periods 1, 2 and 3Population: All randomized participants who received at least 1 dose of study drug and had PSG measurements in Periods 1, 2 and 3.
TST is defined as the total time in sleep epochs from sleep onset time to the end of the primary recording period (8 hours after lights -off). LS mean was calculated using mixed models analysis. The model included factors for treatment, treatment sequence, period and participants.
Outcome measures
| Measure |
0.1 mg LY2624803
n=8 Participants
Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally in Periods 1, 2 and 3.
|
1.0 mg LY2624803
n=17 Participants
Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
3.0 mg LY2624803
n=16 Participants
Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
6.0 mg LY2624803
n=8 Participants
Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
Placebo
n=17 Participants
Single dose of 1 placebo capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
|---|---|---|---|---|---|
|
Total Sleep Time (TST)
|
374.37 min
Interval 333.21 to 415.53
|
404.35 min
Interval 373.53 to 435.17
|
420.65 min
Interval 389.43 to 451.88
|
452.09 min
Interval 411.06 to 493.12
|
373.78 min
Interval 343.12 to 404.44
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 10, 12, 18, and 42 hours post-dose in Period 4Population: All randomized participants who received a single oral dose of LY2624803 in Period 4 and had evaluable PK data.
Outcome measures
| Measure |
0.1 mg LY2624803
n=6 Participants
Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally in Periods 1, 2 and 3.
|
1.0 mg LY2624803
n=5 Participants
Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
3.0 mg LY2624803
n=6 Participants
Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
6.0 mg LY2624803
n=5 Participants
Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
Placebo
Single dose of 1 placebo capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
|---|---|---|---|---|---|
|
PK: Maximum Plasma Concentration (Cmax) of LY2624803 After Single Oral Dose in Period 4
|
4.88 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 10
|
43.8 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 10
|
146 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 13
|
251 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 9
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 10, 12, 18, and 42 hours post-dose in Period 4Population: All randomized participants who received a single oral dose of LY2624803 in Period 4 and had evaluable PK data.
Outcome measures
| Measure |
0.1 mg LY2624803
n=6 Participants
Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally in Periods 1, 2 and 3.
|
1.0 mg LY2624803
n=5 Participants
Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
3.0 mg LY2624803
n=6 Participants
Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
6.0 mg LY2624803
n=5 Participants
Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
Placebo
Single dose of 1 placebo capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
|---|---|---|---|---|---|
|
PK: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of LY2624803 After Single Oral Dose in Period 4
|
79.0 nanograms•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 39
|
714 nanograms•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 20
|
2240 nanograms•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 34
|
4220 nanograms•hour/milliliter (ng•hr/mL)
Geometric Coefficient of Variation 24
|
—
|
Adverse Events
0.1 mg LY2624803 - Periods 1-3
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
1.0 mg LY2624803 - Periods 1-3
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
3.0 mg LY2624803 - Periods 1-3
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
6.0 mg LY2624803 - Periods 1-3
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo - Periods 1-3
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
0.1 mg LY2624803 - Period 4
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
1.0 mg LY2624803 - Period 4
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
3.0 mg LY2624803 - Period 4
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
6 mg LY2624803 - Period 4
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
0.1 mg LY2624803 - Periods 1-3
n=9 participants at risk
Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally in Periods 1, 2 and 3.
|
1.0 mg LY2624803 - Periods 1-3
n=17 participants at risk
Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
3.0 mg LY2624803 - Periods 1-3
n=17 participants at risk
Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
6.0 mg LY2624803 - Periods 1-3
n=8 participants at risk
Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
Placebo - Periods 1-3
n=18 participants at risk
Single dose of 1 placebo capsule plus placebo solution administered orally in Periods 1, 2 and 3.
|
0.1 mg LY2624803 - Period 4
n=6 participants at risk
Single dose of 0.1 mg LY2624803 solution plus 1 placebo capsule administered orally in Period 4.
|
1.0 mg LY2624803 - Period 4
n=5 participants at risk
Single dose of one 1.0 mg LY2624803 capsule plus placebo solution administered orally in Period 4.
|
3.0 mg LY2624803 - Period 4
n=6 participants at risk
Single dose of one 3.0 mg LY2624803 capsule plus placebo solution administered orally in Period 4.
|
6 mg LY2624803 - Period 4
n=5 participants at risk
Single dose of one 6.0 mg LY2624803 capsule plus placebo solution administered orally in Period 4.
|
|---|---|---|---|---|---|---|---|---|---|
|
Eye disorders
Conjunctivitis
|
0.00%
0/9
|
0.00%
0/17
|
5.9%
1/17 • Number of events 1
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/9
|
5.9%
1/17 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
0.00%
0/8
|
5.6%
1/18 • Number of events 1
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
20.0%
1/5 • Number of events 1
|
|
General disorders
Feeling abnormal
|
11.1%
1/9 • Number of events 1
|
0.00%
0/17
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/9
|
0.00%
0/17
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
20.0%
1/5 • Number of events 1
|
0.00%
0/6
|
20.0%
1/5 • Number of events 1
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/9
|
0.00%
0/17
|
5.9%
1/17 • Number of events 1
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
Injury, poisoning and procedural complications
Muscle strain
|
11.1%
1/9 • Number of events 1
|
0.00%
0/17
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/9
|
0.00%
0/17
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
20.0%
1/5 • Number of events 1
|
0.00%
0/6
|
0.00%
0/5
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9
|
0.00%
0/17
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
20.0%
1/5 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/9
|
5.9%
1/17 • Number of events 1
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
Nervous system disorders
Poor quality sleep
|
0.00%
0/9
|
5.9%
1/17 • Number of events 1
|
0.00%
0/17
|
0.00%
0/8
|
11.1%
2/18 • Number of events 3
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
Nervous system disorders
Somnolence
|
0.00%
0/9
|
0.00%
0/17
|
0.00%
0/17
|
0.00%
0/8
|
5.6%
1/18 • Number of events 1
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.1%
1/9 • Number of events 1
|
0.00%
0/17
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Upper airway obstruction
|
0.00%
0/9
|
5.9%
1/17 • Number of events 1
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/5
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/9
|
0.00%
0/17
|
0.00%
0/17
|
0.00%
0/8
|
0.00%
0/18
|
0.00%
0/6
|
20.0%
1/5 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/5
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60