Healthy Volunteers
Conditions
Keywords
Mild Cognitive Impairment
Brief summary
The purpose of this phase I study in healthy participants will be to evaluate the safety and tolerability of LY2886721 single and multiple doses, to evaluate how the body handles the drug, and to evaluate the drug's effect on the body.
Interventions
DRUGLY2886721
Administered orally.
DRUGPlacebo
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy men and non-childbearing potential women * Body mass index (BMI) between 18.0 and 32.0 kilograms per square meter (kg/m\^2) * Are reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures and research unit policies
Exclusion criteria
* Taking over-the-counter or prescription medication with the exception of vitamins or minerals * Smoke more than 10 cigarettes per day * Drink more than 5 cups of caffeine containing beverages (for example, coffee, tea) per day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Effects | Predose up to Day 23 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721 | Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose | — |
| Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721 | Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose | — |
| Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721 | Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose | — |
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15 | Baseline, Day 15 | 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. |
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose | Baseline, 24 hours post-dose | 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. |
| Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose | AUC over the dosing interval at steady state (AUCtau,ss) is reported for participants who received multiple doses of LY2886721. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: once daily (QD) oral dosing for 14 consecutive days | 8 |
| 35 mg LY2886721 Participants received 35 mg LY2886721: oral dosing for 14 consecutive days | 6 |
| 70 mg LY2886721 Participants received 70 mg LY2886721: single oral dose followed by QD oral dosing for 14 consecutive days or single oral dose. | 10 |
| 140 mg LY2886721 Participants received 140 mg LY2886721: single oral dose | 6 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Period 1 | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | 35 mg LY2886721 | 70 mg LY2886721 | 140 mg LY2886721 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 6 Participants | 10 Participants | 6 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 7 Participants | 4 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 4 Participants | 5 Participants | 4 Participants | 19 Participants |
| Region of Enrollment United States | 8 Participants | 6 Participants | 10 Participants | 6 Participants | 30 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 10 Participants | 6 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 8 | 1 / 6 | 3 / 6 | 2 / 10 | 1 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 6 |
Outcome results
Primary
Number of Participants With Clinically Significant Effects
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.
Time frame: Predose up to Day 23
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Effects | 3 Participants |
| 35 mg LY2886721 | Number of Participants With Clinically Significant Effects | 1 Participants |
| 70 mg LY2886721 Multiple Dose | Number of Participants With Clinically Significant Effects | 3 Participants |
| 70 mg LY2886721 Single Dose | Number of Participants With Clinically Significant Effects | 2 Participants |
| 140 mg LY2886721 | Number of Participants With Clinically Significant Effects | 1 Participants |
Secondary
Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose
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.
Time frame: Baseline, 24 hours post-dose
Population: All randomized participants in Cohort C who received placebo or LY2886721 and had measurable CSF amyloid 1-40 concentration data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose | -11.59 Percent change |
| 35 mg LY2886721 | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose | -64.75 Percent change |
| 70 mg LY2886721 Multiple Dose | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose | -72.05 Percent change |
Secondary
Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15
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.
Time frame: Baseline, Day 15
Population: All randomized participants in Cohort B who received multiple doses of placebo or 70 mg LY2886721 and had evaluable CSF amyloid 1-40 concentrations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15 | -0.97 Percent change |
| 35 mg LY2886721 | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15 | -74.46 Percent change |
Secondary
Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721
AUC over the dosing interval at steady state (AUCtau,ss) is reported for participants who received multiple doses of LY2886721.
Time frame: Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose
Population: All randomized participants who received LY2886721 and had evaluable steady-state plasma LY2886721 concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | 1100 ng*hr/mL | Geometric Coefficient of Variation 26 |
| 35 mg LY2886721 | Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | 2400 ng*hr/mL | Geometric Coefficient of Variation 24 |
Secondary
Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721
Time frame: Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
Population: All randomized participants who received a single 70- or 140-mg dose of LY2886721 and had evaluable single-dose LY2886721 concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| 35 mg LY2886721 | Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721 | 4660 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 10 |
Secondary
Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721
Time frame: Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose
Population: All randomized participants who received LY2886721 and had evaluable steady-state plasma LY2886721 concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721 | 112 ng/mL | Geometric Coefficient of Variation 35 |
| 35 mg LY2886721 | Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721 | 230 ng/mL | Geometric Coefficient of Variation 26 |
Secondary
Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721
Time frame: Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
Population: All randomized participants who received a single 70- or 140-mg dose of LY2886721 and had evaluable single-dose LY2886721 concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721 | 182 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| 35 mg LY2886721 | Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721 | 419 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 16 |