Trial Outcomes & Findings for A Safety Study of LY2886721 Multiple Doses in Healthy Subjects (NCT NCT01227252)
NCT ID: NCT01227252
Last Updated: 2019-07-19
Results Overview
Clinically significant effects were defined as serious and nonserious adverse events. A summary of serious and all other nonserious adverse events is located in the Reported Adverse Event module. The number of participants with at least 1 adverse event in each treatment arm is reported for this outcome measure.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
42 participants
Primary outcome timeframe
Predose up to Day 70
Results posted on
2019-07-19
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
10
|
10
|
10
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
12
|
10
|
10
|
10
|
|
Overall Study
COMPLETED
|
12
|
7
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
0
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Overall Study
Sponsor Decision
|
0
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
Baseline Characteristics
A Safety Study of LY2886721 Multiple Doses in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Placebo
n=12 Participants
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
n=10 Participants
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
n=10 Participants
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
n=10 Participants
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
Total
n=42 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
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
42 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
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
39 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
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
14 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
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
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)
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
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
42 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Predose up to Day 70Population: All randomized participants were included in the analysis.
Clinically significant effects were defined as serious and nonserious adverse events. A summary of serious and all other nonserious adverse events is located in the Reported Adverse Event module. The number of participants with at least 1 adverse event in each treatment arm is reported for this outcome measure.
Outcome measures
| Measure |
Placebo
n=12 Participants
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
n=10 Participants
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
n=10 Participants
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
n=10 Participants
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Effects
Serious Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Effects
Nonserious Adverse Events
|
2 Participants
|
2 Participants
|
3 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Predose (Day 14) up to Day 19Population: All participants who received study drug on Day 14 and had evaluable pharmacokinetic data were included in the analysis.
Outcome measures
| Measure |
Placebo
n=9 Participants
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
n=10 Participants
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
n=10 Participants
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Plasma Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY2886721
|
11.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 48
|
43.0 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 24
|
80.0 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 43
|
—
|
SECONDARY outcome
Timeframe: Predose (Day 14) to 24 Hours post-dose (Day 15)Population: All participants who received study drug on Day 14 and had evaluable pharmacokinetic data were included in the analysis.
Area under the concentration versus time curve during 1 dosing interval (1 dosing interval=24 hours) at steady state (AUCτ,ss) is being reported for this outcome measure.
Outcome measures
| Measure |
Placebo
n=9 Participants
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
n=10 Participants
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
n=10 Participants
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721
|
128 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 41
|
447 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 23
|
861 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 38
|
—
|
SECONDARY outcome
Timeframe: Predose (Day 14) up to Day 19Population: All participants who received study drug on Day 14 and had evaluable pharmacodynamic data were included in the analysis.
The minimum concentration (Cnadir) is being reported for this outcome measure.
Outcome measures
| Measure |
Placebo
n=12 Participants
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
n=9 Participants
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
n=10 Participants
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
n=10 Participants
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Plasma Amyloid Beta (Aβ) 1-40 Concentration
|
123 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 14.5
|
49 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 55.1
|
40 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 19.7
|
25 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 28.1
|
SECONDARY outcome
Timeframe: 24 Hours post-dose (Day 15)Population: A subset of all participants who received study drug on Day 14 and had evaluable pharmacodynamic data was included in the analysis.
Outcome measures
| Measure |
Placebo
n=4 Participants
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
n=4 Participants
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
n=4 Participants
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Cerebrospinal Fluid (CSF) Concentration of LY2886721
|
0.5 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 64.5
|
1.4 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 16.6
|
3.8 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 22.6
|
—
|
SECONDARY outcome
Timeframe: Predose (Day 14), 24 Hours post-dose (Day 15)Population: All participants who received study drug on Day 14 and had evaluable pharmacodynamic data were included in the analysis.
The Least Squares means were adjusted for baseline concentration.
Outcome measures
| Measure |
Placebo
n=12 Participants
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
n=10 Participants
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
n=10 Participants
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
n=10 Participants
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration
|
-3.9 percent change (%)
Interval -9.1 to 1.3
|
-11.8 percent change (%)
Interval -16.1 to -7.4
|
-27.5 percent change (%)
Interval -31.6 to -23.5
|
-59.1 percent change (%)
Interval -67.0 to -51.1
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
5 mg LY2886721
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
15 mg LY2886721
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
35 mg LY2886721
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
n=12 participants at risk
Placebo was administered orally as capsules, once daily for 14 days.
|
5 mg LY2886721
n=10 participants at risk
A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
15 mg LY2886721
n=10 participants at risk
A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
35 mg LY2886721
n=10 participants at risk
A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Procedural nausea
|
8.3%
1/12 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
0.00%
0/10
|
|
Gastrointestinal disorders
Gingivitis
|
8.3%
1/12 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
0.00%
0/10
|
|
General disorders
Chest pain
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Oral herpes
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Viral infection
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Injury, poisoning and procedural complications
Procedural headache
|
8.3%
1/12 • Number of events 1
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Investigations
Visual field tests abnormal
|
0.00%
0/12
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/12
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Nervous system disorders
Headache
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Psychiatric disorders
Libido decreased
|
0.00%
0/12
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/12
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/12
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
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