Alzheimer's Disease
Conditions
Brief summary
The purpose of this study is to evaluate the safety and tolerability of the study drug, LY3303560. Side effects and laboratory results will be monitored. This study will involve single doses of LY3303560 administered intravenously (IV), meaning into a vein or subcutaneously (SC), meaning under the skin. Screening is required within 28 days before the start of the study for healthy participants and within 70 days before the start of the study for AD participants. The study requires about 16 weeks of each participant's time including a 4 day clinical research unit (CRU) admission and 10 follow-up appointments. This is the first time that this study drug is being given to participants. This study is for research purposes only, and is not intended to treat any medical condition.
Interventions
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
30 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy males or females of non-childbearing potential and who have given consent and are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * AD participants must be at least 50 years of age and have diagnostic criteria consistent with either mild cognitive impairment due to AD or mild-to moderate AD and have a positive florbetapir positron emission tomography (PET) scan
Exclusion criteria
* Have known allergies to LY3303560, related compounds or any components of the formulation, or history of significant atopy * Have an increased risk of seizures * For AD participants, evidence of macrohemorrhage or greater than 4 microhemorrhage by magnetic resonance imaging (MRI)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | Baseline up to 146 days | Number of participants with one or more SAEs considered by the investigator to be related to study drug administration. A summary of other nonserious adverse events (AEs), and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (Cerebrospinal Fluid): Area Under the Concentration Versus Time Curve (AUC) of LY3303560 in Participants With Alzheimer's' Disease (AD) | Day 1: Predose, 0, 2, 4, 12, 24, and 36 hours post-dose | — |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | Day 1: Predose, 0.5, 2, 4, 12, 24, 48, 72, 96, 120, 144, 360, 528, 696, 1032, 1368, 1704, 2040 hours post-dose; additionally, for 2800 mg and 5600 mg: 2712 and 3384 hours postdose | Serum PK: AUC. Statistical analysis was not pre-specified. |
| PK: Maximum Drug Concentration (Cmax) of LY3303560 | Day 1: Predose, 0.5, 2, 4, 12, 24, 48, 72, 96, 120, 144, 360, 528, 696, 1032, 1368, 1704, 2040 hours post-dose; additionally, for 2800 mg and 5600 mg: 2712 and 3384 hours postdose | Serum PK: Cmax. Statistical analysis was not pre-specified. |
| Pharmacokinetics (Cerebrospinal Fluid): Maximum Drug Concentration (Cmax) of LY3303560 in Participants With Alzheimer's' Disease (AD) | Day 1: Predose, 0, 2, 4, 12, 24, and 36 hours post-dose | — |
| Mean Change From Baseline in QT/QT Corrected (QTc) Interval | Baseline, 7 days postdose | Mean change from baseline in QT/QTc intervals using Fridericia's formula \[Fridericia's corrected QT(QTcF)\] from ECG monitoring. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo single dose administered IV. | 17 |
| 7 mg LY3303560 7 mg LY3303560 single dose administered IV. | 6 |
| 21 mg LY3303560 21 mg LY3303560 single dose administered IV. | 6 |
| 70 mg LY3303560 70 mg LY3303560 single dose administered IV. | 6 |
| 210 mg LY3303560 210 LY3303560 single dose administered IV. | 6 |
| 210 mg LY3303560 SC 210 mg LY3303560 single dose administered SC. | 6 |
| 700 mg LY3303560 700 mg LY3303560 single dose administered IV. | 6 |
| 1400 mg LY3303560 1400 mg LY3303560 single dose administered IV. | 6 |
| 2800 mg LY3303560 2800 mg LY3303560 single dose administered IV. | 7 |
| 5600 mg LY3303560 5600 mg LY3303560 single dose administered IV. | 6 |
| Total | 72 |
Baseline characteristics
| Characteristic | Placebo | Total | 5600 mg LY3303560 | 2800 mg LY3303560 | 1400 mg LY3303560 | 700 mg LY3303560 | 210 mg LY3303560 SC | 210 mg LY3303560 | 70 mg LY3303560 | 21 mg LY3303560 | 7 mg LY3303560 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 9 | 46.7 years STANDARD_DEVIATION 9.9 | 40.7 years STANDARD_DEVIATION 10.4 | 51.7 years STANDARD_DEVIATION 9.6 | 47.0 years STANDARD_DEVIATION 13.5 | 46.3 years STANDARD_DEVIATION 12.2 | 46.2 years STANDARD_DEVIATION 6.7 | 46.3 years STANDARD_DEVIATION 10.3 | 49.8 years STANDARD_DEVIATION 11.2 | 48.5 years STANDARD_DEVIATION 10.7 | 41.8 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 9 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 63 Participants | 4 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants | 5 Participants | 4 Participants |
| Ethnicity (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/Ethnicity, Customized Japanese | 6 Participants | 26 Participants | 3 Participants | 3 Participants | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Non-Japanese | 11 Participants | 46 Participants | 3 Participants | 4 Participants | 2 Participants | 6 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 17 Participants | 72 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 5 Participants | 22 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 50 Participants | 3 Participants | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 6 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 | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 6 / 17 | 1 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 2 / 6 | 3 / 6 | 2 / 6 | 1 / 7 | 4 / 6 |
| serious Total, serious adverse events | 0 / 17 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration
Number of participants with one or more SAEs considered by the investigator to be related to study drug administration. A summary of other nonserious adverse events (AEs), and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline up to 146 days
Population: All enrolled participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 7 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 21 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 70 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 210 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 210 mg LY3303560 SC | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 700 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 1400 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 2800 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
| 5600 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration | 0 Participants |
Secondary
Mean Change From Baseline in QT/QT Corrected (QTc) Interval
Mean change from baseline in QT/QTc intervals using Fridericia's formula \[Fridericia's corrected QT(QTcF)\] from ECG monitoring.
Time frame: Baseline, 7 days postdose
Population: All enrolled participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | 2.5 milliseconds (msec) | Standard Deviation 10.7 |
| 7 mg LY3303560 | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | -0.8 milliseconds (msec) | Standard Deviation 14.8 |
| 21 mg LY3303560 | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | -1.0 milliseconds (msec) | Standard Deviation 8 |
| 70 mg LY3303560 | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | -0.9 milliseconds (msec) | Standard Deviation 4 |
| 210 mg LY3303560 | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | -0.5 milliseconds (msec) | Standard Deviation 11.8 |
| 210 mg LY3303560 SC | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | -1.0 milliseconds (msec) | Standard Deviation 14.7 |
| 700 mg LY3303560 | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | -1.4 milliseconds (msec) | Standard Deviation 14 |
| 1400 mg LY3303560 | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | 1.7 milliseconds (msec) | Standard Deviation 15.2 |
| 2800 mg LY3303560 | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | 5.5 milliseconds (msec) | Standard Deviation 21.3 |
| 5600 mg LY3303560 | Mean Change From Baseline in QT/QT Corrected (QTc) Interval | 0.8 milliseconds (msec) | Standard Deviation 10.9 |
Secondary
Pharmacokinetics (Cerebrospinal Fluid): Area Under the Concentration Versus Time Curve (AUC) of LY3303560 in Participants With Alzheimer's' Disease (AD)
Time frame: Day 1: Predose, 0, 2, 4, 12, 24, and 36 hours post-dose
Population: Zero participants were analyzed as no AD and Mild Cognitive Impairment (MCI) participants were enrolled.
Secondary
Pharmacokinetics (Cerebrospinal Fluid): Maximum Drug Concentration (Cmax) of LY3303560 in Participants With Alzheimer's' Disease (AD)
Time frame: Day 1: Predose, 0, 2, 4, 12, 24, and 36 hours post-dose
Population: Zero participants were analyzed as no AD and MCI participants were enrolled.
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560
Serum PK: AUC. Statistical analysis was not pre-specified.
Time frame: Day 1: Predose, 0.5, 2, 4, 12, 24, 48, 72, 96, 120, 144, 360, 528, 696, 1032, 1368, 1704, 2040 hours post-dose; additionally, for 2800 mg and 5600 mg: 2712 and 3384 hours postdose
Population: All participants who had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 863 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 15 |
| 7 mg LY3303560 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 2570 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 8 |
| 21 mg LY3303560 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 11300 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 16 |
| 70 mg LY3303560 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 27100 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 15 |
| 210 mg LY3303560 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 16700 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 17 |
| 210 mg LY3303560 SC | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 98000 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 34 |
| 700 mg LY3303560 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 219000 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 28 |
| 1400 mg LY3303560 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 325000 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 25 |
| 2800 mg LY3303560 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3303560 | 788000 microgram*hour per millliliter(µg*hr/mL) | Geometric Coefficient of Variation 21 |
Secondary
PK: Maximum Drug Concentration (Cmax) of LY3303560
Serum PK: Cmax. Statistical analysis was not pre-specified.
Time frame: Day 1: Predose, 0.5, 2, 4, 12, 24, 48, 72, 96, 120, 144, 360, 528, 696, 1032, 1368, 1704, 2040 hours post-dose; additionally, for 2800 mg and 5600 mg: 2712 and 3384 hours postdose
Population: All participants who had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 2.78 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 12 |
| 7 mg LY3303560 | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 7.68 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 24 |
| 21 mg LY3303560 | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 41.5 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 57 |
| 70 mg LY3303560 | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 75.0 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 20 |
| 210 mg LY3303560 | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 20.9 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 18 |
| 210 mg LY3303560 SC | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 331 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 18 |
| 700 mg LY3303560 | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 631 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 25 |
| 1400 mg LY3303560 | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 1050 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 30 |
| 2800 mg LY3303560 | PK: Maximum Drug Concentration (Cmax) of LY3303560 | 2440 microgram/millliliter (µg/mL) | Geometric Coefficient of Variation 21 |