Trial Outcomes & Findings for Single Dose Study in Healthy Participants to Investigate the Safety and Absorption of LY2584702 (NCT NCT01372085)
NCT ID: NCT01372085
Last Updated: 2019-01-22
Results Overview
The Cmax following a single oral dose of LY2584702 test formulation \[TF (tablet)\] or reference formulation \[RF (capsule)\] is reported.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
29 participants
Primary outcome timeframe
Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose]
Results posted on
2019-01-22
Participant Flow
Part A: single period, single dose pilot assessed safety, tolerability. Part B: 4-period crossover evaluated bioavailability of 2 drug formulations. Part B, Period (P) 4 participants (pts) separated into 2 cohorts, received drug under fed (P4a) or fasted (P4b) conditions. Pts who withdrew or were withdrawn prior to completing P3 were replaced.
Participant milestones
| Measure |
LY2584702
Participants enrolled in Part A of the study received a single dose of 25 milligrams (mg) LY2584702 (LY) reference formulation \[RF (capsule)\] in a fasted state on Day 1.
|
Placebo
Participants enrolled in Part A of the study received placebo in a fasted state on Day 1.
|
10 mg LY TF, Placebo, 50 mg LY TF, 50 mg LY TF Fed
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 test formulation \[TF (tablet)\], placebo, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
Placebo, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed
Participants enrolled in Part B of the study received a single dose of placebo, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
Placebo, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted
Participants enrolled in Part B of the study received a single dose of placebo, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, Placebo Fasted
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and placebo in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, Placebo, 200 mg LY TF Fasted
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and placebo in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
200 mg LY TF Fasted
Participant enrolled in Part B, Period 4b of the study received a single dose of 200 mg LY2584702 TF in a fasted state on Day 1.
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First Intervention (Period 1)
STARTED
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8
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2
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2
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1
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3
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5
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3
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First Intervention (Period 1)
COMPLETED
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8
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5
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3
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1
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1
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0
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First Intervention (Period 1)
NOT COMPLETED
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0
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0
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0
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0
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Washout Period 1
STARTED
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Washout Period 1
COMPLETED
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Washout Period 1
NOT COMPLETED
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Second Intervention (Period 2)
STARTED
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Second Intervention (Period 2)
COMPLETED
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Second Intervention (Period 2)
NOT COMPLETED
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Washout Period 2
STARTED
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5
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Washout Period 2
COMPLETED
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Washout Period 2
NOT COMPLETED
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Third Intervention (Period 3)
STARTED
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7
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Third Intervention (Period 3)
COMPLETED
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0
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2
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2
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7
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Third Intervention (Period 3)
NOT COMPLETED
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0
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Washout Period 3
STARTED
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2
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7
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Washout Period 3
COMPLETED
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0
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Washout Period 3
NOT COMPLETED
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0
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2
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Forth Intervention (Period 4a/4b)
STARTED
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2
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Forth Intervention (Period 4a/4b)
COMPLETED
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2
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5
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Forth Intervention (Period 4a/4b)
NOT COMPLETED
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0
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0
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Reasons for withdrawal
| Measure |
LY2584702
Participants enrolled in Part A of the study received a single dose of 25 milligrams (mg) LY2584702 (LY) reference formulation \[RF (capsule)\] in a fasted state on Day 1.
|
Placebo
Participants enrolled in Part A of the study received placebo in a fasted state on Day 1.
|
10 mg LY TF, Placebo, 50 mg LY TF, 50 mg LY TF Fed
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 test formulation \[TF (tablet)\], placebo, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
Placebo, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed
Participants enrolled in Part B of the study received a single dose of placebo, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
Placebo, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted
Participants enrolled in Part B of the study received a single dose of placebo, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, Placebo Fasted
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and placebo in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, Placebo, 200 mg LY TF Fasted
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and placebo in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
200 mg LY TF Fasted
Participant enrolled in Part B, Period 4b of the study received a single dose of 200 mg LY2584702 TF in a fasted state on Day 1.
|
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Washout Period 2
Physician Decision
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0
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0
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0
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0
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1
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0
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0
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0
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0
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0
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Washout Period 3
Withdrawal by Subject
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0
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0
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0
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0
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0
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2
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0
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0
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0
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0
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Baseline Characteristics
Single Dose Study in Healthy Participants to Investigate the Safety and Absorption of LY2584702
Baseline characteristics by cohort
| Measure |
Part A (LY2584702)
n=8 Participants
Participants enrolled in Part A of the study received a single dose of 25 milligrams (mg) LY2584702 (LY) reference formulation \[RF (capsule)\] in a fasted state on Day 1.
|
Part A (Placebo)
n=2 Participants
Participants enrolled in Part A of the study received placebo in a fasted state on Day 1.
|
10 mg LY TF, Placebo, 50 mg LY TF, 50 mg LY TF Fed
n=2 Participants
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 test formulation \[TF (tablet)\], placebo, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
Placebo, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed
n=1 Participants
Participants enrolled in Part B of the study received a single dose of placebo, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
Placebo, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted
n=3 Participants
Participants enrolled in Part B of the study received a single dose of placebo, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed
n=7 Participants
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted
n=3 Participants
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, 50 mg LY TF, Placebo Fasted
n=1 Participants
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and placebo in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
10 mg LY TF, 50 mg LY RF, Placebo, 200 mg LY TF Fasted
n=1 Participants
Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and placebo in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods.
|
200 mg LY TF Fasted
n=1 Participants
Participant enrolled in Part B, Period 4b of the study received a single dose of 200 mg LY2584702 TF in a fasted state on Day 1.
|
Total
n=29 Participants
Total of all reporting groups
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|---|---|---|---|---|---|---|---|---|---|---|---|
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Age, Continuous
|
31.9 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
24 years
STANDARD_DEVIATION 4.2 • n=7 Participants
|
44 years
STANDARD_DEVIATION 25.5 • n=5 Participants
|
39 years
n=4 Participants
|
28 years
STANDARD_DEVIATION 8.2 • n=21 Participants
|
34 years
STANDARD_DEVIATION 6.1 • n=8 Participants
|
34 years
STANDARD_DEVIATION 8.9 • n=8 Participants
|
28 years
n=24 Participants
|
35 years
n=42 Participants
|
28 years
n=42 Participants
|
32.6 years
STANDARD_DEVIATION 8.8 • n=42 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
29 Participants
n=42 Participants
|
|
Race/Ethnicity, Customized
Asian
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
29 Participants
n=42 Participants
|
|
Region of Enrollment
Singapore
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
29 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose]Population: Randomized participants in Part A or B of the study who had evaluable Cmax data.
The Cmax following a single oral dose of LY2584702 test formulation \[TF (tablet)\] or reference formulation \[RF (capsule)\] is reported.
Outcome measures
| Measure |
25 mg LY2584702 RF Fasted
n=8 Participants
Participants received a 25 milligram (mg) LY2584702 RF orally in a fasted state on Day 1 in Part A of the study.
|
10 mg LY2584702 TF Fasted
n=12 Participants
Participants received 10 mg of LY2584702 TF orally in a fasted state, in Period 1, Day 1 of Part B of the study.
|
50 mg LY2584702 RF Fasted
n=14 Participants
Participants received 50 mg of LY2584702 RF orally in a fasted state, in Period 2, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fasted
n=16 Participants
Participants received 50 mg of LY2584702 TF orally in a fasted state, in Period 3, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fed
n=8 Participants
Participants received 50 mg of LY2584702 TF orally in a fed state, in Period 4a, Day 1 of Part B of the study.
|
200 mg LY2584702 TF Fasted
n=7 Participants
Participants received 200 mg of LY2584702 TF orally in a fasted state, in Period 4b, Day 1 of Part B of the study.
|
|---|---|---|---|---|---|---|
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Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)
|
266.83 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 71
|
198.22 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 26
|
481.11 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 39
|
668.87 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 26
|
794.13 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 27
|
1486.5 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 11
|
SECONDARY outcome
Timeframe: Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose]Population: Randomized participants in Part A or B of the study who had evaluable AUC data.
AUC from time 0 to the time of the last quantifiable concentration \[AUC(0-tlast)\] and AUC from time 0 to infinity \[AUC(0-inf)\] following a single oral dose of LY2584702 test formulation \[TF (tablet)\] or reference formulation \[RF (capsule)\] is reported.
Outcome measures
| Measure |
25 mg LY2584702 RF Fasted
n=8 Participants
Participants received a 25 milligram (mg) LY2584702 RF orally in a fasted state on Day 1 in Part A of the study.
|
10 mg LY2584702 TF Fasted
n=12 Participants
Participants received 10 mg of LY2584702 TF orally in a fasted state, in Period 1, Day 1 of Part B of the study.
|
50 mg LY2584702 RF Fasted
n=14 Participants
Participants received 50 mg of LY2584702 RF orally in a fasted state, in Period 2, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fasted
n=16 Participants
Participants received 50 mg of LY2584702 TF orally in a fasted state, in Period 3, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fed
n=8 Participants
Participants received 50 mg of LY2584702 TF orally in a fed state, in Period 4a, Day 1 of Part B of the study.
|
200 mg LY2584702 TF Fasted
n=7 Participants
Participants received 200 mg of LY2584702 TF orally in a fasted state, in Period 4b, Day 1 of Part B of the study.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics, Area Under the Concentration-Time Curve (AUC)
AUC(0-tlast)
|
1740 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 63
|
1070 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 26
|
3310 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 43
|
4210 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 25
|
5560 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 30
|
10300 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 20
|
|
Pharmacokinetics, Area Under the Concentration-Time Curve (AUC)
AUC(0-inf)
|
1860 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 58
|
1110 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 27
|
3530 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 43
|
4430 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 25
|
5620 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 29
|
10900 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 20
|
SECONDARY outcome
Timeframe: Part B: Baseline [Periods 1 and 4a (Day -1)], Periods 3, 4a (Day 1). Lipid concentration measurements were performed at time point 0 and 1 hour (h), 3 h, 4 h, 6 h, 10 h, and 24 h.Population: Randomized participants (pts) in Part B of study who had both baseline and postdose total cholesterol measurements. Pts not analyzed for baseline-adjusted change-from-predose total cholesterol levels after single dose placebo, 10-mg, or 200-mg LY2584702 TF or 25-mg or 50-mg LY2584702 RF since they weren't administered in both fasted and fed state.
Baseline-adjusted change-from-predose in lipid concentrations were measured to assess the LY2584702 effect on lipids under different fed states. The 50-milligram (mg) LY2584702 test formulation \[TF (tablet)\] was the only dose and formulation administered in both the fasted and fed states for comparison. Therefore, changes in total cholesterol after single oral doses of placebo, 10-mg, or 200-mg LY2584702 TF or 25-mg or 50-mg LY2584702 reference formulation \[RF (capsule)\] were not calculated. The baseline-adjusted change-from-predose in total cholesterol levels in the fasted and fed state following a single 50-mg LY2584702 TF dose is reported. Baseline was Day -1 of Period 1 for Period 3 fasted state and baseline was Day -1 of Period 4a for Period 4a fed state. Least squares (LS) means was calculated using mixed model repeating measures (MMRM) and adjusted for treatment, time, treatment by time, and participant.
Outcome measures
| Measure |
25 mg LY2584702 RF Fasted
n=13 Participants
Participants received a 25 milligram (mg) LY2584702 RF orally in a fasted state on Day 1 in Part A of the study.
|
10 mg LY2584702 TF Fasted
n=8 Participants
Participants received 10 mg of LY2584702 TF orally in a fasted state, in Period 1, Day 1 of Part B of the study.
|
50 mg LY2584702 RF Fasted
Participants received 50 mg of LY2584702 RF orally in a fasted state, in Period 2, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fasted
Participants received 50 mg of LY2584702 TF orally in a fasted state, in Period 3, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fed
Participants received 50 mg of LY2584702 TF orally in a fed state, in Period 4a, Day 1 of Part B of the study.
|
200 mg LY2584702 TF Fasted
Participants received 200 mg of LY2584702 TF orally in a fasted state, in Period 4b, Day 1 of Part B of the study.
|
|---|---|---|---|---|---|---|
|
Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol)
1-hour postdose
|
-5.62 milligrams per deciliter (mg/dL)
Interval -11.53 to 0.3
|
-2.38 milligrams per deciliter (mg/dL)
Interval -9.91 to 5.16
|
—
|
—
|
—
|
—
|
|
Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol)
3-hours postdose
|
-4.00 milligrams per deciliter (mg/dL)
Interval -9.91 to 1.91
|
-1.75 milligrams per deciliter (mg/dL)
Interval -9.29 to 5.79
|
—
|
—
|
—
|
—
|
|
Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol)
4-hours postdose
|
-4.15 milligrams per deciliter (mg/dL)
Interval -10.07 to 1.76
|
-1.88 milligrams per deciliter (mg/dL)
Interval -9.41 to 5.66
|
—
|
—
|
—
|
—
|
|
Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol)
6-hours postdose
|
-4.77 milligrams per deciliter (mg/dL)
Interval -10.68 to 1.14
|
0.75 milligrams per deciliter (mg/dL)
Interval -6.79 to 8.29
|
—
|
—
|
—
|
—
|
|
Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol)
10-hours postdose
|
-9.23 milligrams per deciliter (mg/dL)
Interval -15.14 to -3.32
|
-5.25 milligrams per deciliter (mg/dL)
Interval -12.79 to 2.29
|
—
|
—
|
—
|
—
|
|
Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol)
24-hours postdose
|
-8.85 milligrams per deciliter (mg/dL)
Interval -14.76 to -2.93
|
-8.75 milligrams per deciliter (mg/dL)
Interval -16.29 to -1.21
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Part A: Baseline [Day 1 (Predose)] and Day 1 (3 h, 4 h, 6 h, and 24 h postdose)Population: Randomized participants in Part A of the study who had both baseline and postdose ECG assessments at each time point. Data was not collected for Placebo group due to insufficient participants (N=2).
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and is calculated from electrocardiogram (ECG) data. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between 2 R waves. Using Fridericia's formula: QTcF = QT/RR\^0.33. The QTcF after single oral doses of LY2584702 reference formulation \[RF (capsule)\] were administered in a fasted state are reported at baseline (Day 1, Predose) and 3 hours (h), 4 h, 6 h, and 24 h postdose.
Outcome measures
| Measure |
25 mg LY2584702 RF Fasted
n=8 Participants
Participants received a 25 milligram (mg) LY2584702 RF orally in a fasted state on Day 1 in Part A of the study.
|
10 mg LY2584702 TF Fasted
Participants received 10 mg of LY2584702 TF orally in a fasted state, in Period 1, Day 1 of Part B of the study.
|
50 mg LY2584702 RF Fasted
Participants received 50 mg of LY2584702 RF orally in a fasted state, in Period 2, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fasted
Participants received 50 mg of LY2584702 TF orally in a fasted state, in Period 3, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fed
Participants received 50 mg of LY2584702 TF orally in a fed state, in Period 4a, Day 1 of Part B of the study.
|
200 mg LY2584702 TF Fasted
Participants received 200 mg of LY2584702 TF orally in a fasted state, in Period 4b, Day 1 of Part B of the study.
|
|---|---|---|---|---|---|---|
|
Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Predose (Baseline)
|
402.8 milliseconds (ms)
Standard Deviation 14.4
|
—
|
—
|
—
|
—
|
—
|
|
Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
3-hours postdose
|
394.8 milliseconds (ms)
Standard Deviation 12.6
|
—
|
—
|
—
|
—
|
—
|
|
Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
4-hours postdose
|
396.6 milliseconds (ms)
Standard Deviation 10.7
|
—
|
—
|
—
|
—
|
—
|
|
Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
6-hours postdose
|
395.7 milliseconds (ms)
Standard Deviation 12.8
|
—
|
—
|
—
|
—
|
—
|
|
Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
24-hours postdose
|
396.1 milliseconds (ms)
Standard Deviation 10.6
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Part B: Baseline [Period 1 (Day -1)] and Periods 1 to 4 (Day 1). Electrocardiograms (ECG) were performed at time point 0 and 3 h, 4 h, 6 h, and 24 h.Population: Randomized participants in Part B of the study who had both baseline and postdose ECG assessments at each time point.
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and is calculated from electrocardiogram (ECG) data. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between 2 R waves. Using Fridericia's formula: QTcF = QT/RR\^0.33. The QTcF after single oral doses of LY2584702 test formulation \[TF (tablet)\], LY2584702 reference formulation \[RF (capsule)\], or placebo were administered in a fasted or fed state are reported at baseline (time-matched Day -1 QTcF) and 3 hours (h), 4 h, 6 h, and 24 h postdose. Day 1, Hour 24 was time-matched with Day-1, Hour 0.
Outcome measures
| Measure |
25 mg LY2584702 RF Fasted
n=12 Participants
Participants received a 25 milligram (mg) LY2584702 RF orally in a fasted state on Day 1 in Part A of the study.
|
10 mg LY2584702 TF Fasted
n=14 Participants
Participants received 10 mg of LY2584702 TF orally in a fasted state, in Period 1, Day 1 of Part B of the study.
|
50 mg LY2584702 RF Fasted
n=16 Participants
Participants received 50 mg of LY2584702 RF orally in a fasted state, in Period 2, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fasted
n=8 Participants
Participants received 50 mg of LY2584702 TF orally in a fasted state, in Period 3, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fed
n=7 Participants
Participants received 50 mg of LY2584702 TF orally in a fed state, in Period 4a, Day 1 of Part B of the study.
|
200 mg LY2584702 TF Fasted
n=8 Participants
Participants received 200 mg of LY2584702 TF orally in a fasted state, in Period 4b, Day 1 of Part B of the study.
|
|---|---|---|---|---|---|---|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day 1, Hour 6
|
413.2 milliseconds (ms)
Standard Deviation 14.8
|
410.6 milliseconds (ms)
Standard Deviation 18.1
|
409.6 milliseconds (ms)
Standard Deviation 14.3
|
414.8 milliseconds (ms)
Standard Deviation 11.5
|
415.6 milliseconds (ms)
Standard Deviation 15.8
|
412.4 milliseconds (ms)
Standard Deviation 16.6
|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day-1, Hour 3 (time-matched baseline)
|
416.1 milliseconds (ms)
Standard Deviation 21.0
|
412.4 milliseconds (ms)
Standard Deviation 19.8
|
413.8 milliseconds (ms)
Standard Deviation 18.2
|
423.3 milliseconds (ms)
Standard Deviation 14.8
|
415.2 milliseconds (ms)
Standard Deviation 22.0
|
415.7 milliseconds (ms)
Standard Deviation 14.2
|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day-1, Hour 0 (time-matched baseline)
|
419.1 milliseconds (ms)
Standard Deviation 21.0
|
413.6 milliseconds (ms)
Standard Deviation 21.5
|
417.1 milliseconds (ms)
Standard Deviation 18.9
|
428.0 milliseconds (ms)
Standard Deviation 11.2
|
415.8 milliseconds (ms)
Standard Deviation 23.5
|
416.4 milliseconds (ms)
Standard Deviation 19.2
|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day 1, Hour 0
|
416.4 milliseconds (ms)
Standard Deviation 17.8
|
413.3 milliseconds (ms)
Standard Deviation 23.0
|
414.4 milliseconds (ms)
Standard Deviation 17.7
|
407.8 milliseconds (ms)
Standard Deviation 16.2
|
413.1 milliseconds (ms)
Standard Deviation 22.1
|
412.1 milliseconds (ms)
Standard Deviation 19.8
|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day 1, Hour 3
|
413.6 milliseconds (ms)
Standard Deviation 17.8
|
410.6 milliseconds (ms)
Standard Deviation 23.2
|
409.2 milliseconds (ms)
Standard Deviation 16.2
|
402.6 milliseconds (ms)
Standard Deviation 10.0
|
409.9 milliseconds (ms)
Standard Deviation 22.1
|
412.3 milliseconds (ms)
Standard Deviation 17.8
|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day-1, Hour 4 (time-matched baseline)
|
415.5 milliseconds (ms)
Standard Deviation 20.6
|
413.1 milliseconds (ms)
Standard Deviation 20.7
|
414.6 milliseconds (ms)
Standard Deviation 18.3
|
420.7 milliseconds (ms)
Standard Deviation 10.1
|
418.3 milliseconds (ms)
Standard Deviation 24.2
|
413.4 milliseconds (ms)
Standard Deviation 17.1
|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day 1, Hour 4
|
414.8 milliseconds (ms)
Standard Deviation 17.7
|
412.0 milliseconds (ms)
Standard Deviation 21.0
|
409.2 milliseconds (ms)
Standard Deviation 14.0
|
407.3 milliseconds (ms)
Standard Deviation 12.1
|
413.3 milliseconds (ms)
Standard Deviation 20.4
|
415.2 milliseconds (ms)
Standard Deviation 19.3
|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day-1, Hour 6 (time-matched baseline)
|
417.1 milliseconds (ms)
Standard Deviation 20.6
|
415.0 milliseconds (ms)
Standard Deviation 19.8
|
417.6 milliseconds (ms)
Standard Deviation 19.3
|
420.5 milliseconds (ms)
Standard Deviation 12.5
|
422.3 milliseconds (ms)
Standard Deviation 24.0
|
418.1 milliseconds (ms)
Standard Deviation 16.8
|
|
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
Day 1, Hour 24
|
415.4 milliseconds (ms)
Standard Deviation 19.4
|
408.9 milliseconds (ms)
Standard Deviation 19.0
|
409.1 milliseconds (ms)
Standard Deviation 13.9
|
411.1 milliseconds (ms)
Standard Deviation 13.5
|
409.0 milliseconds (ms)
Standard Deviation 17.9
|
409.0 milliseconds (ms)
Standard Deviation 19.8
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
25 mg LY2584702 RF Fasted
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
10 mg LY2584702 TF Fasted
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
50 mg LY2584702 RF Fasted
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
50 mg LY2584702 TF Fasted
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
50 mg LY2584702 TF Fed
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
200 mg LY2584702 TF Fasted
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=10 participants at risk
Participants received placebo orally in fasted state on Day 1 in Part A and Periods 1 to 4, Day 1 in Part B of the study.
|
25 mg LY2584702 RF Fasted
n=8 participants at risk
Participants received a 25 milligram (mg) LY2584702 reference formulation \[RF (capsule)\] orally in a fasted state on Day 1 in Part A of the study.
|
10 mg LY2584702 TF Fasted
n=12 participants at risk
Participants received 10 mg of LY2584702 test formulation \[TF (tablet)\] orally in a fasted state, in Period 1, Day 1 of Part B of the study.
|
50 mg LY2584702 RF Fasted
n=14 participants at risk
Participants received 50 mg of LY2584702 RF orally in a fasted state, in Period 2, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fasted
n=16 participants at risk
Participants received 50 mg of LY2584702 TF orally in a fasted state, in Period 3, Day 1 of Part B of the study.
|
50 mg LY2584702 TF Fed
n=8 participants at risk
Participants received 50 mg of LY2584702 TF orally in a fed state, in Period 4a, Day 1 of Part B of the study.
|
200 mg LY2584702 TF Fasted
n=7 participants at risk
Participants received 200 mg of LY2584702 TF orally in a fasted state, in Period 4b, Day 1 of Part B of the study.
|
|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Bradycardia
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
14.3%
1/7 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
General disorders
Catheter site haematoma
|
10.0%
1/10 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
General disorders
Catheter site pain
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
General disorders
Catheter site related reaction
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
7.1%
1/14 • Number of events 1
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
General disorders
Fatigue
|
0.00%
0/10
|
0.00%
0/8
|
8.3%
1/12 • Number of events 1
|
0.00%
0/14
|
0.00%
0/16
|
12.5%
1/8 • Number of events 1
|
0.00%
0/7
|
|
General disorders
Vessel puncture site haematoma
|
0.00%
0/10
|
25.0%
2/8 • Number of events 3
|
8.3%
1/12 • Number of events 2
|
0.00%
0/14
|
0.00%
0/16
|
12.5%
1/8 • Number of events 1
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
14.3%
1/7 • Number of events 1
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
10.0%
1/10 • Number of events 1
|
37.5%
3/8 • Number of events 3
|
0.00%
0/12
|
7.1%
1/14 • Number of events 1
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
8.3%
1/12 • Number of events 1
|
0.00%
0/14
|
6.2%
1/16 • Number of events 1
|
25.0%
2/8 • Number of events 2
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/10
|
0.00%
0/8
|
8.3%
1/12 • Number of events 1
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/10
|
0.00%
0/8
|
8.3%
1/12 • Number of events 1
|
0.00%
0/14
|
6.2%
1/16 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/10
|
0.00%
0/8
|
8.3%
1/12 • Number of events 1
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/12
|
7.1%
1/14 • Number of events 1
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/14
|
0.00%
0/16
|
0.00%
0/8
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/12
|
0.00%
0/14
|
6.2%
1/16 • Number of events 1
|
0.00%
0/8
|
0.00%
0/7
|
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