Trial Outcomes & Findings for A Study of LY2886721 in Healthy Participants and Participants Diagnosed With Alzheimer's Disease (NCT NCT01807026)
NCT ID: NCT01807026
Last Updated: 2019-07-19
Results Overview
AUC0-∞ following administration of a single dose of 70 or 280 mg LY2886721.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
Predose through 96 hours after administration of study drug
Results posted on
2019-07-19
Participant Flow
Participant milestones
| Measure |
Cohort A: 70 mg LY2886721
Participants with Alzheimer's disease received a single, 70-milligrams (mg) (1 capsule), oral dose of LY2886721.
|
Cohort A: Placebo
Participants with Alzheimer's disease received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
Cohort B: 70 mg LY2886721
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: Placebo
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: Placebo
Healthy participants received a single, oral dose of LY2886721-matching placebo (4 capsules).
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
2
|
10
|
2
|
9
|
3
|
|
Overall Study
Received at Least One Dose of Study Drug
|
10
|
2
|
10
|
2
|
9
|
3
|
|
Overall Study
COMPLETED
|
10
|
2
|
10
|
2
|
9
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of LY2886721 in Healthy Participants and Participants Diagnosed With Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Cohort A: 70 mg LY2886721
n=10 Participants
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort A: Placebo
n=2 Participants
Participants with Alzheimer's disease received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
Cohort B: 70 mg LY2886721
n=10 Participants
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: Placebo
n=2 Participants
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
Cohort C: 280 mg LY2886721
n=9 Participants
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: Placebo
n=3 Participants
Healthy participants received a single, oral dose of LY2886721-matching placebo (4 capsules).
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
70.1 years
STANDARD_DEVIATION 12.6 • n=5 Participants
|
67.0 years
STANDARD_DEVIATION 18.4 • n=7 Participants
|
59.3 years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
54.5 years
STANDARD_DEVIATION 3.5 • n=4 Participants
|
29.3 years
STANDARD_DEVIATION 11.3 • n=21 Participants
|
21.3 years
STANDARD_DEVIATION 0.6 • n=10 Participants
|
51.8 years
STANDARD_DEVIATION 20.7 • n=115 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
14 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
22 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
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
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
White
|
10 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
35 Participants
n=115 Participants
|
|
Region of Enrollment
United States
|
10 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
36 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: Predose through 96 hours after administration of study drugPopulation: Participants who received at least one dose of LY2886721 and with evaluable plasma LY2886721-concentration data.
AUC0-∞ following administration of a single dose of 70 or 280 mg LY2886721.
Outcome measures
| Measure |
Cohort A: 70 mg LY2886721
n=10 Participants
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: 70 mg LY2886721
n=10 Participants
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
n=9 Participants
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohorts B and C: Placebo
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
|---|---|---|---|---|---|
|
Pharmacokinetics: Area Under the Curve Extrapolated to Infinity (AUC0-∞) of Plasma LY2886721
|
2800 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 25
|
2580 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 20
|
10500 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 22
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose through 96 hours after administration of study drugPopulation: Participants who received at least one dose of LY2886721 and with evaluable plasma LY2886721-concentration data.
Cmax following administration of a single dose of 70 or 280 mg LY2886721.
Outcome measures
| Measure |
Cohort A: 70 mg LY2886721
n=10 Participants
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: 70 mg LY2886721
n=10 Participants
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
n=9 Participants
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohorts B and C: Placebo
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
|---|---|---|---|---|---|
|
Pharmacokinetics: Maximum Concentration (Cmax) of Plasma LY2886721
|
183 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 41
|
180 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 17
|
888 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 11
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose through 36 hours after administration of study drugPopulation: Participants who received at least one dose of LY2886721 at the 70-mg dose level and with evaluable CSF LY2886721-concentration data.
AUC0-∞ following administration of a single dose of 70 mg LY2886721.
Outcome measures
| Measure |
Cohort A: 70 mg LY2886721
n=10 Participants
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: 70 mg LY2886721
n=10 Participants
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohorts B and C: Placebo
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
|---|---|---|---|---|---|
|
Pharmacokinetics: Area Under the Curve Extrapolated to Infinity (AUC0-∞) of Cerebrospinal Fluid (CSF) LY2886721
|
458 ng*h/mL
Geometric Coefficient of Variation 16
|
410 ng*h/mL
Geometric Coefficient of Variation 16
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose through 36 hours after administration of study drugPopulation: Participants who received at least one dose of LY2886721 at the 70-mg dose level and with evaluable CSF LY2886721-concentration data.
Cmax following administration of a single dose of 70 mg LY2886721.
Outcome measures
| Measure |
Cohort A: 70 mg LY2886721
n=10 Participants
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: 70 mg LY2886721
n=10 Participants
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohorts B and C: Placebo
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
|---|---|---|---|---|---|
|
Pharmacokinetics: Maximum Concentration (Cmax) of CSF LY2886721
|
24.0 ng/mL
Geometric Coefficient of Variation 18
|
24.4 ng/mL
Geometric Coefficient of Variation 19
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose, up to 96 hours after administration of study drugPopulation: Participants who received at least one dose of LY2886721 or placebo and had evaluable plasma Aβ 1-40 data.
Plasma concentration of Aβ1-40 was summarized based on lowest observed concentration (Cnadir).
Outcome measures
| Measure |
Cohort A: 70 mg LY2886721
n=10 Participants
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: 70 mg LY2886721
n=2 Participants
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
n=10 Participants
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
n=9 Participants
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohorts B and C: Placebo
n=5 Participants
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
|---|---|---|---|---|---|
|
Pharmacodynamics (PD): Cnadir of Plasma Amyloid β (Aβ)1-40
|
22.2 picograms/milliliter (pg/mL)
Geometric Coefficient of Variation 35.2
|
140 picograms/milliliter (pg/mL)
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation not reported since n \<3.
|
19.5 picograms/milliliter (pg/mL)
Geometric Coefficient of Variation 11.9
|
11.0 picograms/milliliter (pg/mL)
Geometric Coefficient of Variation 42.2
|
162 picograms/milliliter (pg/mL)
Geometric Coefficient of Variation 7.39
|
PRIMARY outcome
Timeframe: Predose up to 36 hours after administration of study drugPopulation: Participants who received at least one dose of LY2886721 at the 70-mg dose level or placebo and had evaluable CSF Aβ 1-40 data.
Plasma concentration of Aβ1-40 was summarized based on Cnadir following administration of a single dose of 70 mg LY2886721 or a single dose of LY2886721-matching placebo.
Outcome measures
| Measure |
Cohort A: 70 mg LY2886721
n=10 Participants
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: 70 mg LY2886721
n=2 Participants
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
n=10 Participants
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
n=2 Participants
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohorts B and C: Placebo
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
|---|---|---|---|---|---|
|
PD: Cnadir of CSF Aβ 1-40
|
7600 pg/mL
Geometric Coefficient of Variation 30.7
|
19500 pg/mL
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation not reported since n \<3.
|
4480 pg/mL
Geometric Coefficient of Variation 110
|
12500 pg/mL
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation not reported since n \<3.
|
—
|
SECONDARY outcome
Timeframe: Predose up to 48 hours after administration of study drugPopulation: Participants who received at least one dose of LY2886721 at the 280-mg dose level and with evaluable mean QTcF data.
The mean QTcF value at Cmax for participants administered a single dose of 280 mg LY2886721 was reported. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Time matched mean change from baseline in QTcF = time matched plasma concentration + participant + random error.
Outcome measures
| Measure |
Cohort A: 70 mg LY2886721
n=9 Participants
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: 70 mg LY2886721
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: 280 mg LY2886721
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohorts B and C: Placebo
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
|---|---|---|---|---|---|
|
Cohort C: Mean QTcF Value at Cmax
|
28.3 milliseconds (ms)
Interval 23.4 to 33.2
|
—
|
—
|
—
|
—
|
Adverse Events
Cohort A: 70 mg LY2886721
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort A: Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort B: 70 mg LY2886721
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Cohort B: Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort C: 280 mg LY2886721
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort C: Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort A: 70 mg LY2886721
n=10 participants at risk
Participants with Alzheimer's disease received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort A: Placebo
n=2 participants at risk
Participants with Alzheimer's disease received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
Cohort B: 70 mg LY2886721
n=10 participants at risk
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
|
Cohort B: Placebo
n=2 participants at risk
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
|
Cohort C: 280 mg LY2886721
n=9 participants at risk
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
|
Cohort C: Placebo
n=3 participants at risk
Healthy participants received a single, oral dose of LY2886721-matching placebo (4 capsules).
|
|---|---|---|---|---|---|---|
|
Eye disorders
Photophobia
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/10
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10
|
0.00%
0/2
|
30.0%
3/10 • Number of events 3
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
General disorders
Fatigue
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
General disorders
Pain
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Investigations
Red blood cells csf positive
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/10
|
0.00%
0/2
|
20.0%
2/10 • Number of events 2
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Nervous system disorders
Headache
|
30.0%
3/10 • Number of events 3
|
50.0%
1/2 • Number of events 2
|
60.0%
6/10 • Number of events 7
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Nervous system disorders
Migraine
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Nervous system disorders
Presyncope
|
0.00%
0/10
|
0.00%
0/2
|
0.00%
0/10
|
0.00%
0/2
|
11.1%
1/9 • Number of events 5
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.00%
0/10
|
0.00%
0/2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/10
|
50.0%
1/2 • Number of events 1
|
0.00%
0/10
|
0.00%
0/2
|
0.00%
0/9
|
0.00%
0/3
|
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