Healthy
Conditions
Brief summary
The main purpose of this study is to assess how fast donanemab (LY3002813) gets into the blood stream and how long it takes the body to remove it when administered as single dose in healthy participants. The study will also evaluate the safety and tolerability of donanemab. The study will last up to approximately 22 weeks.
Interventions
DRUGDonanemab
Administered IV.
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants who are overtly healthy as determined by medical evaluation * Have a body mass index (BMI) of 19.0 and 32.0, kilograms per meter squared (kg/m²), inclusive. * Females of childbearing potential will be excluded from the study.
Exclusion criteria
* Have allergies to either humanized monoclonal antibodies, diphenhydramine, epinephrine, or methylprednisolone * Have a history within the past 5 years of a primary or recurrent malignant disease * Have used over-the-counter or prescription medications, including herbal medication, within 7 days prior to dosing * Are pregnant or intend to become pregnant or to breastfeed during the study * Smoke more than 10 cigarettes per day or are unable to abide by investigative site smoking restrictions * Have a history of intracranial hemorrhage, cerebrovascular aneurysm or arteriovenous malformation, carotid, carotid artery occlusion, stroke or epilepsy or family history of dementia or Down's syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Four Weeks (AUC[0-4 Weeks]) of Donanemab (i.e) Period 2, Period 4, Period 6. | Predose, end of infusion, 24, 48, 72, 96, 168, 336 hours post-dose on days 1, 15, 29, 43, 57, 71 | As per the prespecified analysis, AUC\[0-4 weeks\] will be calculated as the sum of AUC0-2weeks for: * treatment period 1 and 2 (dosing days 1, 15 respectively) represented as period 2 * treatment period 3 and 4 (dosing days 29, 43 respectively) represented as period 4 * treatment period 5 and 6 (dosing days 57, 71 respectively) represented as period 6. |
| PK: Maximum Observed Concentration During a Dosing Interval at Steady State (Cmax, ss) of Donanemab | Predose, end of infusion, 24, 48, 72, 96, 168, 336 hours post-dose on day 71 | PK: Cmax, ss of Donanemab |
| PK: Area Under the Concentration Versus Time Curve During a Dosing Interval at Steady State (AUCτ,ss) of Donanemab | Predose, end of infusion, 24, 48, 72, 96, 168, 336 hours post-dose on day 71 | PK: AUCτ,ss of Donanemab |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Donanemab Participants received a 350 mg IV infusion of donanemab every two weeks for six treatment periods (1 to 6), each lasting two weeks. Treatments were administered on the first day of each period, i.e., days 1, 15, 29, 43, 57, and 71. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Protocol deviation | 1 |
Baseline characteristics
| Characteristic | Donanemab |
|---|---|
| Age, Continuous | 28.9 years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 42 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 42 |
| other Total, other adverse events | 22 / 42 |
| serious Total, serious adverse events | 0 / 42 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Four Weeks (AUC[0-4 Weeks]) of Donanemab (i.e) Period 2, Period 4, Period 6.
As per the prespecified analysis, AUC\[0-4 weeks\] will be calculated as the sum of AUC0-2weeks for: * treatment period 1 and 2 (dosing days 1, 15 respectively) represented as period 2 * treatment period 3 and 4 (dosing days 29, 43 respectively) represented as period 4 * treatment period 5 and 6 (dosing days 57, 71 respectively) represented as period 6.
Time frame: Predose, end of infusion, 24, 48, 72, 96, 168, 336 hours post-dose on days 1, 15, 29, 43, 57, 71
Population: All enrolled participants who received at least one IV infusion of donanemab and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Donanemab | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Four Weeks (AUC[0-4 Weeks]) of Donanemab (i.e) Period 2, Period 4, Period 6. | Period 6 | 15500 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 45 |
| Donanemab | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Four Weeks (AUC[0-4 Weeks]) of Donanemab (i.e) Period 2, Period 4, Period 6. | Period 2 | 17300 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 23 |
| Donanemab | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Four Weeks (AUC[0-4 Weeks]) of Donanemab (i.e) Period 2, Period 4, Period 6. | Period 4 | 15400 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 32 |
Primary
PK: Area Under the Concentration Versus Time Curve During a Dosing Interval at Steady State (AUCτ,ss) of Donanemab
PK: AUCτ,ss of Donanemab
Time frame: Predose, end of infusion, 24, 48, 72, 96, 168, 336 hours post-dose on day 71
Population: All enrolled participants who received at least one IV infusion of donanemab and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Donanemab | PK: Area Under the Concentration Versus Time Curve During a Dosing Interval at Steady State (AUCτ,ss) of Donanemab | 7590 μg*h/mL | Geometric Coefficient of Variation 50 |
Primary
PK: Maximum Observed Concentration During a Dosing Interval at Steady State (Cmax, ss) of Donanemab
PK: Cmax, ss of Donanemab
Time frame: Predose, end of infusion, 24, 48, 72, 96, 168, 336 hours post-dose on day 71
Population: All enrolled participants who received at least one IV infusion of donanemab and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Donanemab | PK: Maximum Observed Concentration During a Dosing Interval at Steady State (Cmax, ss) of Donanemab | 112 μg/mL | Geometric Coefficient of Variation 21 |