Trial Outcomes & Findings for A Safety Study of LY2886721 Single Doses in Healthy Subjects (NCT NCT01133405)
NCT ID: NCT01133405
Last Updated: 2019-09-16
Results Overview
A summary of serious adverse events and other nonserious adverse events located in Reported Adverse Event section. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in other LY2886721 groups received LY2886721 in fasted state. Due to crossover design in Part 1, results reported by treatment; thus, participants are included in multiple arms.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
Predose to 10-14 days after final dose of study drug (up to 42 days)
Results posted on
2019-09-16
Participant Flow
The study consists of 2-parts. Part A was a cross-over study and was conducted in 2 alternating cohorts (Cohorts A and B). Part B was a single-dose, single period study in 2 cohorts (Cohorts C and D). All doses were administered in the fasted state, unless otherwise indicated. Each oral dose was followed by a washout period of at least 14 days.
Participant milestones
| Measure |
Cohort A (Part 1) : Sequence 1
Participants received Placebo, 15 milligram (mg) LY2886721 and 35 mg LY2886721 orally as per the below dosing sequence in each period.
Period 1: Placebo, Period 2: 15 mg LY2886721 and Period 3: 35 mg LY2886721.
|
Cohort A (Part 1): Sequence 2
Participants received 1 mg LY2886721, 15 mg LY2886721 and placebo orally as per the below dosing sequence in each period.
Period 1: 1 mg LY2886721, Period 2: 15 mg LY2886721 and Period 3: Placebo.
|
Cohort A (Part 1): Sequence 3
Participants received 1 mg LY2886721, placebo and 35 mg LY2886721 orally as per the below dosing sequence in each period.
Period 1: 1 mg LY2886721, Period 2: Placebo and Period 3: 35 mg LY2886721.
|
Cohort B (Part 1): Sequence 1
Participants received 7 mg LY2886721, 25 mg LY2886721 and placebo and orally as per the below dosing sequence in each period.
Period 1: 7 mg LY2886721, Period 2: 25 mg LY2886721 and Period 3: Placebo.
|
Cohort B (Part 1): Sequence 2
Participants received 7 mg LY2886721, placebo and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period.
Period 1: 7 mg LY2886721 Period 2: Placebo and Period 3: 7 mg LY2886721 (fed state).
|
Cohort B (Part 1): Sequence 3
Participants received Placebo, 25 mg LY2886721 and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period.
Period 1: Placebo, Period 2: 25 mg LY2886721 and Period 3: 7 mg LY2886721 (fed state).
|
Cohort C (Part 2): 10mg LY2886721
Participants received a single 10 mg LY2886721 oral dose (low dose) in the fasted state.
|
Cohort C (Part 2): Placebo
Participants received a single oral placebo dose in the fasted state.
|
Cohort D (Part 2): 35 mg LY2886721
Participants received a single 35 mg LY2886721 oral dose (high dose) in the fasted state.
|
Cohort D (Part 2): Placebo
Participants received a single oral placebo dose in the fasted state.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
3
|
6
|
5
|
5
|
3
|
5
|
5
|
2
|
4
|
2
|
|
Period 1
Safety Analysis Population
|
2
|
6
|
5
|
5
|
3
|
5
|
5
|
2
|
4
|
2
|
|
Period 1
Received at Least 1 Dose of Drug
|
2
|
4
|
4
|
3
|
3
|
4
|
4
|
2
|
4
|
2
|
|
Period 1
COMPLETED
|
2
|
3
|
4
|
1
|
3
|
3
|
4
|
2
|
4
|
2
|
|
Period 1
NOT COMPLETED
|
1
|
3
|
1
|
4
|
0
|
2
|
1
|
0
|
0
|
0
|
|
Period 2
STARTED
|
2
|
4
|
4
|
3
|
3
|
4
|
0
|
0
|
0
|
0
|
|
Period 2
Received at Least 1 Dose of Study Drug
|
2
|
4
|
4
|
3
|
3
|
4
|
0
|
0
|
0
|
0
|
|
Period 2
COMPLETED
|
2
|
3
|
3
|
2
|
3
|
2
|
0
|
0
|
0
|
0
|
|
Period 2
NOT COMPLETED
|
0
|
1
|
1
|
1
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
2
|
4
|
4
|
2
|
3
|
2
|
0
|
0
|
0
|
0
|
|
Period 3
Received at Least 1 Dose of Study Drug
|
2
|
4
|
4
|
2
|
3
|
2
|
0
|
0
|
0
|
0
|
|
Period 3
COMPLETED
|
2
|
4
|
4
|
2
|
3
|
2
|
0
|
0
|
0
|
0
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort A (Part 1) : Sequence 1
Participants received Placebo, 15 milligram (mg) LY2886721 and 35 mg LY2886721 orally as per the below dosing sequence in each period.
Period 1: Placebo, Period 2: 15 mg LY2886721 and Period 3: 35 mg LY2886721.
|
Cohort A (Part 1): Sequence 2
Participants received 1 mg LY2886721, 15 mg LY2886721 and placebo orally as per the below dosing sequence in each period.
Period 1: 1 mg LY2886721, Period 2: 15 mg LY2886721 and Period 3: Placebo.
|
Cohort A (Part 1): Sequence 3
Participants received 1 mg LY2886721, placebo and 35 mg LY2886721 orally as per the below dosing sequence in each period.
Period 1: 1 mg LY2886721, Period 2: Placebo and Period 3: 35 mg LY2886721.
|
Cohort B (Part 1): Sequence 1
Participants received 7 mg LY2886721, 25 mg LY2886721 and placebo and orally as per the below dosing sequence in each period.
Period 1: 7 mg LY2886721, Period 2: 25 mg LY2886721 and Period 3: Placebo.
|
Cohort B (Part 1): Sequence 2
Participants received 7 mg LY2886721, placebo and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period.
Period 1: 7 mg LY2886721 Period 2: Placebo and Period 3: 7 mg LY2886721 (fed state).
|
Cohort B (Part 1): Sequence 3
Participants received Placebo, 25 mg LY2886721 and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period.
Period 1: Placebo, Period 2: 25 mg LY2886721 and Period 3: 7 mg LY2886721 (fed state).
|
Cohort C (Part 2): 10mg LY2886721
Participants received a single 10 mg LY2886721 oral dose (low dose) in the fasted state.
|
Cohort C (Part 2): Placebo
Participants received a single oral placebo dose in the fasted state.
|
Cohort D (Part 2): 35 mg LY2886721
Participants received a single 35 mg LY2886721 oral dose (high dose) in the fasted state.
|
Cohort D (Part 2): Placebo
Participants received a single oral placebo dose in the fasted state.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Period 1
Withdrawal by Subject
|
0
|
1
|
0
|
1
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Period 1
Physician Decision
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 1
Discontinued after randomization
|
1
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Period 1
Received drug only in period 2
|
0
|
1
|
0
|
2
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Period 1
Received drug only in period 3
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Period 2
Entry Criteria Not Met
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
Physician Decision
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Safety Study of LY2886721 Single Doses in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Cohort A (Part 1): Sequence 1
n=2 Participants
Participants received Placebo, 15 milligram (mg) LY2886721 and 35 mg LY2886721 orally as per the dosing sequence in each period.
|
Cohort A (Part 1): Sequence 2
n=6 Participants
Participants received 1 mg LY2886721, 15 mg LY2886721 and placebo orally as per the dosing sequence in each period.
|
Cohort A (Part 1): Sequence 3
n=5 Participants
Participants received 1 mg LY2886721, placebo and 35 mg LY2886721 orally as per the dosing sequence in each period.
|
Cohort B (Part 1): Sequence 1
n=5 Participants
Participants received 7 mg LY2886721, 25 mg LY2886721 and placebo and orally as per the dosing sequence in each period.
|
Cohort B (Part 1): Sequence 2
n=3 Participants
Participants received 7 mg LY2886721, placebo and 7 mg LY2886721 (fed state) orally as per the dosing sequence in each period.
|
Cohort B (Part 1): Sequence 3
n=5 Participants
Participants received Placebo, 25 mg LY2886721 and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period.
|
Cohort C (Part 2): 10mg LY2886721
n=5 Participants
Participants received a single 10 mg LY2886721 oral dose (low dose) in the fasted state.
|
Cohort C (Part 2): Placebo
n=2 Participants
.Participants received a single oral placebo dose in the fasted state.
|
Cohort D (Part 2): 35 mg LY2886721
n=4 Participants
Participants received a single 35 mg LY2886721 oral dose (high dose) in the fasted state.
|
Cohort D (Part 2): Placebo
n=2 Participants
Participants received a single oral placebo dose in the fasted state.
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
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
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
39 Participants
n=42 Participants
|
|
Age, Categorical
>=65 years
|
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
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
7 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
32 Participants
n=42 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
11 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
13 Participants
n=42 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
2 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
11 Participants
n=42 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 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
|
2 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
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
|
|
Region of Enrollment
United States
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
39 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: Predose to 10-14 days after final dose of study drug (up to 42 days)Population: 39 of the 40 participants who were entered and randomized into the study and who had undergone study procedures were included in the safety analyses. One participant, who was entered and randomized into the study but did not undergo study procedures, was excluded from the analysis.
A summary of serious adverse events and other nonserious adverse events located in Reported Adverse Event section. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in other LY2886721 groups received LY2886721 in fasted state. Due to crossover design in Part 1, results reported by treatment; thus, participants are included in multiple arms.
Outcome measures
| Measure |
Placebo (Part 1)
n=19 Participants
In a single 8-day period, participants received a single placebo oral dose after an overnight fast.
|
1 mg LY2886721 (Part 1)
n=8 Participants
In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast.
|
7 mg LY2886721 (Part 1 - Fed and Fasted)
n=8 Participants
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed).
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted).
|
10 mg LY2886721 (Part 2)
n=4 Participants
Participants received a single 10-mg LY2886721 oral dose after an overnight fast.
|
15 mg LY2886721 (Part 1)
n=6 Participants
In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast.
|
25 mg LY2886721 (Part 1)
n=7 Participants
In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 1)
n=6 Participants
In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 2)
n=4 Participants
Participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
Placebo (Part 2)
n=4 Participants
Participants received a single placebo oral dose after an overnight fast.
|
|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Effects (Adverse Events)
Serious Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Effects (Adverse Events)
Other Nonserious Adverse Events
|
4 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dosePopulation: All participants who received at least 1 dose of LY2886721 and have evaluable pharmacokinetic data were included in the analysis. One participant from Part 2, who experienced an adverse event before receiving study medication, was not included in the analysis.
To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms.
Outcome measures
| Measure |
Placebo (Part 1)
n=8 Participants
In a single 8-day period, participants received a single placebo oral dose after an overnight fast.
|
1 mg LY2886721 (Part 1)
n=5 Participants
In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast.
|
7 mg LY2886721 (Part 1 - Fed and Fasted)
n=6 Participants
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed).
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted).
|
10 mg LY2886721 (Part 2)
n=4 Participants
Participants received a single 10-mg LY2886721 oral dose after an overnight fast.
|
15 mg LY2886721 (Part 1)
n=6 Participants
In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast.
|
25 mg LY2886721 (Part 1)
n=7 Participants
In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 1)
n=6 Participants
In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 2)
n=4 Participants
Participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
Placebo (Part 2)
Participants received a single placebo oral dose after an overnight fast.
|
|---|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of LY2886721
|
1.9 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 65
|
22.5 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
18.2 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 64
|
6.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 60
|
41.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 24
|
79.1 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 25
|
78.2 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 45
|
53.3 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 44
|
—
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dosePopulation: All participants who received at least 1 dose of LY2886721 and have evaluable pharmacokinetic data were included in the analysis. One participant in Part 2, who experienced an adverse event before receiving study medication, was not included in the analysis.
Pharmacokinetic AUC for LY2886721 from time 0 to infinity. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms.
Outcome measures
| Measure |
Placebo (Part 1)
n=8 Participants
In a single 8-day period, participants received a single placebo oral dose after an overnight fast.
|
1 mg LY2886721 (Part 1)
n=5 Participants
In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast.
|
7 mg LY2886721 (Part 1 - Fed and Fasted)
n=6 Participants
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed).
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted).
|
10 mg LY2886721 (Part 2)
n=4 Participants
Participants received a single 10-mg LY2886721 oral dose after an overnight fast.
|
15 mg LY2886721 (Part 1)
n=6 Participants
In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast.
|
25 mg LY2886721 (Part 1)
n=7 Participants
In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 1)
n=6 Participants
In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 2)
n=4 Participants
Participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
Placebo (Part 2)
Participants received a single placebo oral dose after an overnight fast.
|
|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC)
|
NA nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation NA
Data for the 1-mg LY2886721 group are not presented for this outcome measure because sufficient data did not exist for the terminal elimination phase calculations.
|
311 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 14
|
212 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 41
|
144 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 580
|
468 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 20
|
926 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 16
|
954 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 37
|
800 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 38
|
—
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dosePopulation: All participants who received at least 1 dose of LY2886721 in Part 1 and have evaluable pharmacodynamic data were included in the analysis. One participant who was entered and randomized into the study but did not undergo study procedures, was excluded from the analysis.
Plasma concentrations of Aβ1-40 were based on the lowest observed/measured concentration (Cnadir). To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms.
Outcome measures
| Measure |
Placebo (Part 1)
n=19 Participants
In a single 8-day period, participants received a single placebo oral dose after an overnight fast.
|
1 mg LY2886721 (Part 1)
n=8 Participants
In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast.
|
7 mg LY2886721 (Part 1 - Fed and Fasted)
n=6 Participants
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed).
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted).
|
10 mg LY2886721 (Part 2)
n=6 Participants
Participants received a single 10-mg LY2886721 oral dose after an overnight fast.
|
15 mg LY2886721 (Part 1)
n=7 Participants
In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast.
|
25 mg LY2886721 (Part 1)
n=6 Participants
In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 2)
Participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
Placebo (Part 2)
Participants received a single placebo oral dose after an overnight fast.
|
|---|---|---|---|---|---|---|---|---|---|
|
Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only)
|
121 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 23.6
|
80 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 19.5
|
56 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 41.3
|
35 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 37.7
|
34 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 28.4
|
36 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 11.7
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose and up to 36 hours postdosePopulation: All participants who received at least 1 dose of LY2886721 in Part 2 and have evaluable pharmacokinetic data were included in the analysis. One participant, who experienced an adverse event before receiving study medication, was not included in the analysis.
Outcome measures
| Measure |
Placebo (Part 1)
n=4 Participants
In a single 8-day period, participants received a single placebo oral dose after an overnight fast.
|
1 mg LY2886721 (Part 1)
n=4 Participants
In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast.
|
7 mg LY2886721 (Part 1 - Fed and Fasted)
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed).
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted).
|
10 mg LY2886721 (Part 2)
Participants received a single 10-mg LY2886721 oral dose after an overnight fast.
|
15 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast.
|
25 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 2)
Participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
Placebo (Part 2)
Participants received a single placebo oral dose after an overnight fast.
|
|---|---|---|---|---|---|---|---|---|---|
|
Cerebrospinal Fluid (CSF) Maximum Observed Drug Concentration (Cmax) of LY2886721 (Part 2 Only)
|
0.93 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 60
|
5.99 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 39
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose and up to 36 hours postdosePopulation: All participants who received at least 1 dose of LY2886721 in Part 2 and have evaluable pharmacodynamic data were included in the analysis. One participant, who experienced an adverse event before receiving study medication, was not included in the analysis.
CSF Aβ 1-40 concentration was based on the lowest observed/measured concentration (Cnadir).
Outcome measures
| Measure |
Placebo (Part 1)
n=4 Participants
In a single 8-day period, participants received a single placebo oral dose after an overnight fast.
|
1 mg LY2886721 (Part 1)
n=4 Participants
In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast.
|
7 mg LY2886721 (Part 1 - Fed and Fasted)
n=4 Participants
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed).
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted).
|
10 mg LY2886721 (Part 2)
Participants received a single 10-mg LY2886721 oral dose after an overnight fast.
|
15 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast.
|
25 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 2)
Participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
Placebo (Part 2)
Participants received a single placebo oral dose after an overnight fast.
|
|---|---|---|---|---|---|---|---|---|---|
|
Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only)
|
8080 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 48.8
|
5650 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 51.1
|
7150 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 62.4
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose and up to 36 hours postdosePopulation: All participants who received at least 1 dose of LY2886721 in Part 2 and have evaluable pharmacokinetic data were included in the analysis. One participant, who experienced an adverse event before receiving study medication, was not included in the analysis.
Outcome measures
| Measure |
Placebo (Part 1)
n=4 Participants
In a single 8-day period, participants received a single placebo oral dose after an overnight fast.
|
1 mg LY2886721 (Part 1)
n=4 Participants
In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast.
|
7 mg LY2886721 (Part 1 - Fed and Fasted)
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed).
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted).
|
10 mg LY2886721 (Part 2)
Participants received a single 10-mg LY2886721 oral dose after an overnight fast.
|
15 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast.
|
25 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 1)
In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 2)
Participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
Placebo (Part 2)
Participants received a single placebo oral dose after an overnight fast.
|
|---|---|---|---|---|---|---|---|---|---|
|
Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only)
|
27 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 89
|
121 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 30
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Placebo (Part 1)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
1 mg LY2886721 (Part 1)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
7 mg LY2886721 (Part 1 - Fed and Fasted)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
10 mg LY2886721 (Part 2)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
15 mg LY2886721 (Part 1)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
25 mg LY2886721 (Part 1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
35 mg LY2886721 (Part 1)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
35 mg LY2886721 (Part 2)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo (Part 2)
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 |
Placebo (Part 1)
n=19 participants at risk
In a single 8-day period, participants received a single placebo oral dose after an overnight fast.
|
1 mg LY2886721 (Part 1)
n=8 participants at risk
In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast.
|
7 mg LY2886721 (Part 1 - Fed and Fasted)
n=8 participants at risk
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after breakfast (Fed).
In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted).
|
10 mg LY2886721 (Part 2)
n=4 participants at risk
Participants received a single 10-mg LY2886721 oral dose after an overnight fast.
|
15 mg LY2886721 (Part 1)
n=6 participants at risk
In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast.
|
25 mg LY2886721 (Part 1)
n=7 participants at risk
In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 1)
n=6 participants at risk
In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
35 mg LY2886721 (Part 2)
n=4 participants at risk
Participants received a single 35-mg LY2886721 oral dose after an overnight fast.
|
Placebo (Part 2)
n=4 participants at risk
Participants received a single placebo oral dose after an overnight fast.
|
|---|---|---|---|---|---|---|---|---|---|
|
Ear and labyrinth disorders
Ear discomfort
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/19
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
|
General disorders
Chest pain
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
|
General disorders
Puncture site pain
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
25.0%
1/4 • Number of events 2
|
0.00%
0/4
|
|
General disorders
Vessel puncture site haematoma
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
|
Injury, poisoning and procedural complications
Procedural headache
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
100.0%
4/4 • Number of events 5
|
25.0%
1/4 • Number of events 1
|
|
Injury, poisoning and procedural complications
Procedural vomiting
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
|
Nervous system disorders
Dizziness
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/19
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
|
Nervous system disorders
Headache
|
5.3%
1/19 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/19
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
5.3%
1/19 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/4
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60