Alzheimer's Disease
Conditions
Brief summary
This is a Phase 1 study in healthy subjects to evaluate the safety and tolerability of LY2886721 multiple doses, how the body handles the drug, and the drug's effect on the body.
Interventions
DRUGPlacebo
Administered orally as capsules, daily for 14 days
DRUGLY2886721
5 milligrams (mg) up to 35 mg, administered orally as capsules, daily for 14 days
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 between 18.0-32.0 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 70 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY2886721 | Predose (Day 14) up to Day 19 | — |
| Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | Predose (Day 14) to 24 Hours post-dose (Day 15) | 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. |
| Plasma Amyloid Beta (Aβ) 1-40 Concentration | Predose (Day 14) up to Day 19 | The minimum concentration (Cnadir) is being reported for this outcome measure. |
| Cerebrospinal Fluid (CSF) Concentration of LY2886721 | 24 Hours post-dose (Day 15) | — |
| Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration | Predose (Day 14), 24 Hours post-dose (Day 15) | The Least Squares means were adjusted for baseline concentration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo was administered orally as capsules, once daily for 14 days. | 12 |
| 5 mg LY2886721 A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days. | 10 |
| 15 mg LY2886721 A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days. | 10 |
| 35 mg LY2886721 A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days. | 10 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | 5 mg LY2886721 | 15 mg LY2886721 | 35 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 | 12 Participants | 10 Participants | 10 Participants | 10 Participants | 42 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 2 Participants | 3 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 5 Participants | 6 Participants | 20 Participants |
| Region of Enrollment United States | 12 Participants | 10 Participants | 10 Participants | 10 Participants | 42 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 12 Participants | 9 Participants | 9 Participants | 9 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 12 | 2 / 10 | 3 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Number of Participants With Clinically Significant Effects
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.
Time frame: Predose up to Day 70
Population: All randomized participants were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 2 Participants |
| 5 mg LY2886721 | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 2 Participants |
| 5 mg LY2886721 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| 15 mg LY2886721 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| 15 mg LY2886721 | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 3 Participants |
| 35 mg LY2886721 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| 35 mg LY2886721 | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 3 Participants |
Secondary
Cerebrospinal Fluid (CSF) Concentration of LY2886721
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cerebrospinal Fluid (CSF) Concentration of LY2886721 | 0.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 64.5 |
| 5 mg LY2886721 | Cerebrospinal Fluid (CSF) Concentration of LY2886721 | 1.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 16.6 |
| 15 mg LY2886721 | Cerebrospinal Fluid (CSF) Concentration of LY2886721 | 3.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22.6 |
Secondary
Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration
The Least Squares means were adjusted for baseline concentration.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration | -3.9 percent change (%) |
| 5 mg LY2886721 | Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration | -11.8 percent change (%) |
| 15 mg LY2886721 | Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration | -27.5 percent change (%) |
| 35 mg LY2886721 | Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration | -59.1 percent change (%) |
Secondary
Plasma Amyloid Beta (Aβ) 1-40 Concentration
The minimum concentration (Cnadir) is being reported for this outcome measure.
Time frame: Predose (Day 14) up to Day 19
Population: All participants who received study drug on Day 14 and had evaluable pharmacodynamic data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Amyloid Beta (Aβ) 1-40 Concentration | 123 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 14.5 |
| 5 mg LY2886721 | Plasma Amyloid Beta (Aβ) 1-40 Concentration | 49 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 55.1 |
| 15 mg LY2886721 | Plasma Amyloid Beta (Aβ) 1-40 Concentration | 40 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 19.7 |
| 35 mg LY2886721 | Plasma Amyloid Beta (Aβ) 1-40 Concentration | 25 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 28.1 |
Secondary
Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | 128 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 41 |
| 5 mg LY2886721 | Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | 447 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 23 |
| 15 mg LY2886721 | Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | 861 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 38 |
Secondary
Plasma Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY2886721
Time frame: Predose (Day 14) up to Day 19
Population: All participants who received study drug on Day 14 and had evaluable pharmacokinetic data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY2886721 | 11.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| 5 mg LY2886721 | Plasma Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY2886721 | 43.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| 15 mg LY2886721 | Plasma Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY2886721 | 80.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 43 |