Single-Dose, Dose-Escalation Study With LY3303560 to Evaluate the Safety, Tolerability, and Pharmacokinetics in Healthy Subjects and Patients With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild to Moderate Alzheimer's Disease
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 72
- Locations
- 2
- Primary Endpoint
- Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 30 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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)
Arms & Interventions
LY3303560
Single IV infusion 7 milligram (mg), 21 mg, 70 mg, 210 mg, 700 mg, 1400 mg, 2800 mg, and 5600 mg of LY3303560 on Day 1 in healthy participants.
Intervention: LY3303560 - IV (Drug)
Saline Solution
Single IV infusion of saline solution to match LY3303560 on Day 1 in healthy participants.
Intervention: Saline Solution - IV (Drug)
LY3303560 Subcutaneous (SC)
Single SC injection of 210 mg LY3303560 on Day 1 in healthy participants.
Intervention: LY3303560 - SC (Drug)
Outcomes
Primary Outcomes
Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration
Time Frame: 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 Outcomes
- Mean Change From Baseline in QT/QT Corrected (QTc) Interval(Baseline, 7 days postdose)
- 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)
- 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)
- 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)
- 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)