Alzheimer's Disease
Conditions
Brief summary
This is a Phase 1 study in healthy subjects to evaluate the safety and tolerability of LY2886721 single doses, how the body handles the drug, and the drug's effect on the body.
Detailed description
This is a Phase 1 study with 2 parts, both in healthy subjects. Part 1 is a subject- and investigator-blind, placebo-controlled, randomized, 3-period, crossover study. Part 1 will assess the safety and tolerability of LY2886721 single doses, how the body handles the drug, and the drug's effect on the body. Part 2 is a subject- and investigator-blind, placebo-controlled, randomized study to assess the safety and tolerability of an LY2886721 single dose, how the body handles the drug, and the drug's effect on the body including in cerebrospinal fluid.
Interventions
DRUGLY2886721
Oral capsules
DRUGPlacebo
Oral capsules
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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 nonchild-bearing potential women * 20 years or older * Body mass index between 18-32 kilograms per square meter (kg/m\^2)
Exclusion criteria
* Taking over-the-counter or prescription medication with the exception of vitamins or minerals or stable doses of thyroid or estrogen hormone replacement * Smoke more than 10 cigarettes per day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Effects (Adverse Events) | Predose to 10-14 days after final dose of study drug (up to 42 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose | 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. |
| Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose | 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. |
| Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose | 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. |
| Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only) | Predose and up to 36 hours postdose | CSF Aβ 1-40 concentration was based on the lowest observed/measured concentration (Cnadir). |
| Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only) | Predose and up to 36 hours postdose | — |
| Cerebrospinal Fluid (CSF) Maximum Observed Drug Concentration (Cmax) of LY2886721 (Part 2 Only) | Predose and up to 36 hours postdose | — |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A (Part 1): Sequence 1 Participants received Placebo, 15 milligram (mg) LY2886721 and 35 mg LY2886721 orally as per the dosing sequence in each period. | 2 |
| Cohort A (Part 1): Sequence 2 Participants received 1 mg LY2886721, 15 mg LY2886721 and placebo orally as per the dosing sequence in each period. | 6 |
| Cohort A (Part 1): Sequence 3 Participants received 1 mg LY2886721, placebo and 35 mg LY2886721 orally as per the dosing sequence in each period. | 5 |
| Cohort B (Part 1): Sequence 1 Participants received 7 mg LY2886721, 25 mg LY2886721 and placebo and orally as per the dosing sequence in each period. | 5 |
| Cohort B (Part 1): Sequence 2 Participants received 7 mg LY2886721, placebo and 7 mg LY2886721 (fed state) orally as per the dosing sequence in each period. | 3 |
| 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. | 5 |
| Cohort C (Part 2): 10mg LY2886721 Participants received a single 10 mg LY2886721 oral dose (low dose) in the fasted state. | 5 |
| Cohort C (Part 2): Placebo .Participants received a single oral placebo dose in the fasted state. | 2 |
| Cohort D (Part 2): 35 mg LY2886721 Participants received a single 35 mg LY2886721 oral dose (high dose) in the fasted state. | 4 |
| Cohort D (Part 2): Placebo Participants received a single oral placebo dose in the fasted state. | 2 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 | Discontinued after randomization | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 1 | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 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 1 | Withdrawal by Subject | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 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 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort A (Part 1): Sequence 2 | Cohort A (Part 1): Sequence 1 | Cohort A (Part 1): Sequence 3 | Cohort B (Part 1): Sequence 1 | Cohort B (Part 1): Sequence 2 | Cohort B (Part 1): Sequence 3 | Cohort C (Part 2): 10mg LY2886721 | Cohort C (Part 2): Placebo | Cohort D (Part 2): 35 mg LY2886721 | Cohort D (Part 2): Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 6 Participants | 2 Participants | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 5 Participants | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 39 Participants | 6 Participants | 2 Participants | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 5 Participants | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 7 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 32 Participants | 6 Participants | 2 Participants | 2 Participants | 5 Participants | 1 Participants | 5 Participants | 4 Participants | 1 Participants | 4 Participants | 2 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 19 | 2 / 8 | 1 / 8 | 1 / 4 | 0 / 6 | 1 / 7 | 3 / 6 | 4 / 4 | 3 / 4 |
| serious Total, serious adverse events | 0 / 19 | 0 / 8 | 0 / 8 | 0 / 4 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Number of Participants With Clinically Significant Effects (Adverse Events)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| Placebo (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 4 Participants |
| 1 mg LY2886721 (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| 1 mg LY2886721 (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 2 Participants |
| 7 mg LY2886721 (Part 1 - Fed and Fasted) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| 7 mg LY2886721 (Part 1 - Fed and Fasted) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 1 Participants |
| 10 mg LY2886721 (Part 2) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| 10 mg LY2886721 (Part 2) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 1 Participants |
| 15 mg LY2886721 (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| 15 mg LY2886721 (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 0 Participants |
| 25 mg LY2886721 (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 1 Participants |
| 25 mg LY2886721 (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| 35 mg LY2886721 (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 3 Participants |
| 35 mg LY2886721 (Part 1) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| 35 mg LY2886721 (Part 2) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| 35 mg LY2886721 (Part 2) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 4 Participants |
| Placebo (Part 2) | Number of Participants With Clinically Significant Effects (Adverse Events) | Serious Adverse Events | 0 Participants |
| Placebo (Part 2) | Number of Participants With Clinically Significant Effects (Adverse Events) | Other Nonserious Adverse Events | 3 Participants |
Secondary
Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only)
Time frame: Predose and up to 36 hours postdose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part 1) | 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 |
| 1 mg LY2886721 (Part 1) | Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only) | 121 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 30 |
Secondary
Cerebrospinal Fluid (CSF) Maximum Observed Drug Concentration (Cmax) of LY2886721 (Part 2 Only)
Time frame: Predose and up to 36 hours postdose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part 1) | 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 |
| 1 mg LY2886721 (Part 1) | Cerebrospinal Fluid (CSF) Maximum Observed Drug Concentration (Cmax) of LY2886721 (Part 2 Only) | 5.99 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
Secondary
Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only)
CSF Aβ 1-40 concentration was based on the lowest observed/measured concentration (Cnadir).
Time frame: Predose and up to 36 hours postdose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part 1) | 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 |
| 1 mg LY2886721 (Part 1) | Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only) | 5650 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 51.1 |
| 7 mg LY2886721 (Part 1 - Fed and Fasted) | Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only) | 7150 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 62.4 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of LY2886721
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.
Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part 1) | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 1.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 65 |
| 1 mg LY2886721 (Part 1) | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 22.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| 7 mg LY2886721 (Part 1 - Fed and Fasted) | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 18.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 64 |
| 10 mg LY2886721 (Part 2) | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 6.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 60 |
| 15 mg LY2886721 (Part 1) | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 41.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| 25 mg LY2886721 (Part 1) | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 79.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| 35 mg LY2886721 (Part 1) | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 78.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45 |
| 35 mg LY2886721 (Part 2) | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 53.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
Secondary
Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only)
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.
Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part 1) | Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 121 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 23.6 |
| 1 mg LY2886721 (Part 1) | Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 80 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 19.5 |
| 7 mg LY2886721 (Part 1 - Fed and Fasted) | Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 56 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 41.3 |
| 10 mg LY2886721 (Part 2) | Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 35 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 37.7 |
| 15 mg LY2886721 (Part 1) | Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 34 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 28.4 |
| 25 mg LY2886721 (Part 1) | Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 36 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 11.7 |
Secondary
Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC)
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.
Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part 1) | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | NA nanogram*hour per milliliter (ng*h/mL) | — |
| 1 mg LY2886721 (Part 1) | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 311 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 14 |
| 7 mg LY2886721 (Part 1 - Fed and Fasted) | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 212 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 41 |
| 10 mg LY2886721 (Part 2) | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 144 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 580 |
| 15 mg LY2886721 (Part 1) | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 468 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 20 |
| 25 mg LY2886721 (Part 1) | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 926 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 16 |
| 35 mg LY2886721 (Part 1) | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 954 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 37 |
| 35 mg LY2886721 (Part 2) | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 800 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 38 |