Trial Outcomes & Findings for A Study of LY2886721 in Healthy Participants (NCT NCT01534273)
NCT ID: NCT01534273
Last Updated: 2019-08-28
Results Overview
Data presented are the number of participants who experienced treatment-emergent adverse events. A summary of serious adverse events and other non-serious adverse events, regardless of causality is reported in the Adverse Events module.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
Predose up to Day 23
Results posted on
2019-08-28
Participant Flow
Participant milestones
| Measure |
Placebo (Cohort A)
Placebo: once daily (QD) oral dosing for 14 consecutive days
|
35 mg LY2886721 (Cohort A)
35 milligrams (mg) LY2886721: QD oral dosing for 14 consecutive days
|
Placebo (Cohort B)
Placebo: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2)
|
70 mg LY2886721 (Cohort B)
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2)
|
Placebo (Cohort C)
Placebo: single oral dose
|
70 mg LY2886721 (Cohort C)
70 mg LY2886721: single oral dose
|
140 mg LY2886721 (Cohort C)
140 mg LY2886721: single oral dose
|
|---|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
3
|
6
|
2
|
7
|
3
|
3
|
6
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
3
|
6
|
2
|
7
|
3
|
3
|
6
|
|
Period 1
COMPLETED
|
3
|
6
|
2
|
6
|
3
|
3
|
6
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Period 2
STARTED
|
0
|
0
|
2
|
6
|
0
|
0
|
0
|
|
Period 2
COMPLETED
|
0
|
0
|
2
|
6
|
0
|
0
|
0
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Placebo (Cohort A)
Placebo: once daily (QD) oral dosing for 14 consecutive days
|
35 mg LY2886721 (Cohort A)
35 milligrams (mg) LY2886721: QD oral dosing for 14 consecutive days
|
Placebo (Cohort B)
Placebo: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2)
|
70 mg LY2886721 (Cohort B)
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2)
|
Placebo (Cohort C)
Placebo: single oral dose
|
70 mg LY2886721 (Cohort C)
70 mg LY2886721: single oral dose
|
140 mg LY2886721 (Cohort C)
140 mg LY2886721: single oral dose
|
|---|---|---|---|---|---|---|---|
|
Period 1
Physician Decision
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Study of LY2886721 in Healthy Participants
Baseline characteristics by cohort
| Measure |
Placebo
n=8 Participants
Placebo: once daily (QD) oral dosing for 14 consecutive days
|
35 mg LY2886721
n=6 Participants
Participants received 35 mg LY2886721: oral dosing for 14 consecutive days
|
70 mg LY2886721
n=10 Participants
Participants received 70 mg LY2886721: single oral dose followed by QD oral dosing for 14 consecutive days or single oral dose.
|
140 mg LY2886721
n=6 Participants
Participants received 140 mg LY2886721: single oral dose
|
Total
n=30 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
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
30 Participants
n=21 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
|
|
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
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Ethnicity (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
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
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
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 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
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
19 Participants
n=21 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
|
|
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
|
|
Region of Enrollment
United States
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Predose up to Day 23Population: All enrolled participants. Ten participants, 7 in Cohort B and 3 in Cohort C, received 70 mg LY2886721 as a single dose. Six of the participants in Cohort B went on to receive QD dosing for 14 consecutive days. These 6 participants are included in the 70 mg LY2886721 Single Dose arm and the 70 mg LY2886721 Multiple Dose arm.
Data presented are the number of participants who experienced treatment-emergent adverse events. A summary of serious adverse events and other non-serious adverse events, regardless of causality is reported in the Adverse Events module.
Outcome measures
| Measure |
Placebo
n=8 Participants
Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)
|
35 mg LY2886721
n=6 Participants
35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)
|
70 mg LY2886721 Multiple Dose
n=6 Participants
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
|
70 mg LY2886721 Single Dose
n=10 Participants
70 mg LY2886721: single oral dose (Cohort B \[Period 1\] and Cohort C)
|
140 mg LY2886721
n=6 Participants
140 mg LY2886721: single oral dose (Cohort C)
|
|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Effects
|
3 Participants
|
1 Participants
|
3 Participants
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdosePopulation: All randomized participants who received a single 70- or 140-mg dose of LY2886721 and had evaluable single-dose LY2886721 concentration data.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)
|
35 mg LY2886721
n=6 Participants
35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)
|
70 mg LY2886721 Multiple Dose
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
|
70 mg LY2886721 Single Dose
70 mg LY2886721: single oral dose (Cohort B \[Period 1\] and Cohort C)
|
140 mg LY2886721
140 mg LY2886721: single oral dose (Cohort C)
|
|---|---|---|---|---|---|
|
Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721
|
182 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 26
|
419 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 16
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdosePopulation: All randomized participants who received a single 70- or 140-mg dose of LY2886721 and had evaluable single-dose LY2886721 concentration data.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)
|
35 mg LY2886721
n=6 Participants
35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)
|
70 mg LY2886721 Multiple Dose
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
|
70 mg LY2886721 Single Dose
70 mg LY2886721: single oral dose (Cohort B \[Period 1\] and Cohort C)
|
140 mg LY2886721
140 mg LY2886721: single oral dose (Cohort C)
|
|---|---|---|---|---|---|
|
Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721
|
2110 nanograms*hours/milliliter (ng*hr/mL)
Geometric Coefficient of Variation 23
|
4660 nanograms*hours/milliliter (ng*hr/mL)
Geometric Coefficient of Variation 10
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdosePopulation: All randomized participants who received LY2886721 and had evaluable steady-state plasma LY2886721 concentration data.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)
|
35 mg LY2886721
n=6 Participants
35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)
|
70 mg LY2886721 Multiple Dose
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
|
70 mg LY2886721 Single Dose
70 mg LY2886721: single oral dose (Cohort B \[Period 1\] and Cohort C)
|
140 mg LY2886721
140 mg LY2886721: single oral dose (Cohort C)
|
|---|---|---|---|---|---|
|
Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721
|
112 ng/mL
Geometric Coefficient of Variation 35
|
230 ng/mL
Geometric Coefficient of Variation 26
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdosePopulation: All randomized participants who received LY2886721 and had evaluable steady-state plasma LY2886721 concentration data.
AUC over the dosing interval at steady state (AUCtau,ss) is reported for participants who received multiple doses of LY2886721.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)
|
35 mg LY2886721
n=6 Participants
35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)
|
70 mg LY2886721 Multiple Dose
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
|
70 mg LY2886721 Single Dose
70 mg LY2886721: single oral dose (Cohort B \[Period 1\] and Cohort C)
|
140 mg LY2886721
140 mg LY2886721: single oral dose (Cohort C)
|
|---|---|---|---|---|---|
|
Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721
|
1100 ng*hr/mL
Geometric Coefficient of Variation 26
|
2400 ng*hr/mL
Geometric Coefficient of Variation 24
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 15Population: All randomized participants in Cohort B who received multiple doses of placebo or 70 mg LY2886721 and had evaluable CSF amyloid 1-40 concentrations.
Least squares (LS) mean percent changes from baseline to Day 15 in CSF amyloid 1-40 concentrations for participants in Cohort B are reported. LS means were calculated from an analysis of covariance (ANCOVA) with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% confidence interval (CI) of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline.
Outcome measures
| Measure |
Placebo
n=2 Participants
Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)
|
35 mg LY2886721
n=6 Participants
35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)
|
70 mg LY2886721 Multiple Dose
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
|
70 mg LY2886721 Single Dose
70 mg LY2886721: single oral dose (Cohort B \[Period 1\] and Cohort C)
|
140 mg LY2886721
140 mg LY2886721: single oral dose (Cohort C)
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15
|
-0.97 Percent change
Interval -5.81 to 3.87
|
-74.46 Percent change
Interval -77.25 to -71.67
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 24 hours post-dosePopulation: All randomized participants in Cohort C who received placebo or LY2886721 and had measurable CSF amyloid 1-40 concentration data.
LS mean percent changes from baseline to 24 hours post-dose in CSF amyloid 1-40 concentrations for participants in Cohort C are reported. LS means were calculated from an ANCOVA with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% CI of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline.
Outcome measures
| Measure |
Placebo
n=3 Participants
Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)
|
35 mg LY2886721
n=3 Participants
35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)
|
70 mg LY2886721 Multiple Dose
n=6 Participants
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
|
70 mg LY2886721 Single Dose
70 mg LY2886721: single oral dose (Cohort B \[Period 1\] and Cohort C)
|
140 mg LY2886721
140 mg LY2886721: single oral dose (Cohort C)
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose
|
-11.59 Percent change
Interval -24.5 to 1.32
|
-64.75 Percent change
Interval -76.38 to -53.13
|
-72.05 Percent change
Interval -80.36 to -63.74
|
—
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
35 mg LY2886721
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
70 mg LY2886721 Multiple Dose
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
70 mg LY2886721 Single Dose
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
140 mg LY2886721
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=8 participants at risk
Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)
|
35 mg LY2886721
n=6 participants at risk
35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)
|
70 mg LY2886721 Multiple Dose
n=6 participants at risk
70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
|
70 mg LY2886721 Single Dose
n=10 participants at risk
70 mg LY2886721: single oral dose(Cohort B \[Period 1\] and Cohort C)
|
140 mg LY2886721
n=6 participants at risk
140 mg LY2886721: single oral dose (Cohort C)
|
|---|---|---|---|---|---|
|
Eye disorders
Scotoma
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/10
|
0.00%
0/6
|
|
Gastrointestinal disorders
Dry mouth
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/10
|
0.00%
0/6
|
|
General disorders
Fatigue
|
0.00%
0/8
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/10
|
0.00%
0/6
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/10
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Procedural dizziness
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Injury, poisoning and procedural complications
Procedural headache
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/10
|
16.7%
1/6 • Number of events 1
|
|
Investigations
Liver function test abnormal
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/6
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/6
|
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