Single-Dose and Multiple-Dose, Dose-Escalation Study With LY2599666 to Evaluate the Safety, Pharmacokinetics, and Tolerability in Healthy Subjects and Patients With Mild Cognitive Impairment Due to Alzheimer's Disease and Mild-to-Moderate Alzheimer's Disease
Overview
- Phase
- Phase 1
- Intervention
- Placebo IV
- Conditions
- Healthy
- Sponsor
- Eli Lilly and Company
- Enrollment
- 50
- Locations
- 4
- Primary Endpoint
- Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY2599666 in different groups of people - those who are healthy, those who have mild cognitive impairment due to Alzheimer's Disease (AD), and those with mild-to-moderate AD. The study will measure how much LY2599666 gets into the bloodstream and how long it takes the body to get rid of it. It will also evaluate how LY2599666 affects the body. The study has three parts. Part A will last about 2 months. Parts B and C will each last about 23 weeks. Participants may only enroll in one part.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy Participants Part A:
- •Overtly healthy males or females as determined by medical history and physical examination
- •Have a body mass index (BMI) between 18.0 and 32.0 kilograms per meter squared (kg/m²), inclusive
- •Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) \[Part B and C\]:
- •Participants are at least 50 years old at screening
- •Present with Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild-to-moderate AD
- •Have a caregiver/study informant who provides a separate written informed consent to participate
- •Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator
- •Positive florbetapir scan
Exclusion Criteria
- •All Participants
- •Are currently enrolled in a clinical trial involving an investigational product or off-label use of a drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- •Have known allergies to LY2599666, solanezumab, or any related compounds or components of the formulations, or have a history of significant atopy
- •Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
- •Have an abnormal blood pressure as determined by the investigator
- •Have significant allergies to humanized monoclonal antibodies, diphenhydramine, epinephrine, or methylprednisone
- •Require treatment with other monoclonal antibodies
- •Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) \[Part B and C\]
- •Have medical or surgical conditions in which lumbar puncture and or/catheter insertion is contraindicated
- •Have any contraindication for magnetic resonance imaging (MRI) studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI
Arms & Interventions
Placebo (Part C)
Placebo given IV once weekly or once every 4 weeks for 12 weeks.
Intervention: Placebo IV
Placebo (Part B)
Placebo given SC once weekly for 12 weeks (13 doses).
Intervention: Placebo SC
Solanezumab (Part C)
Solanezumab given intravenously (IV) once weekly or once every 4 weeks for 12 weeks.
Intervention: Solanezumab
LY2599666 (Part A)
LY2599666 given subcutaneously (SC) once.
Intervention: LY2599666
Placebo (Part A)
Placebo matching LY2599666 given SC once.
Intervention: Placebo SC
LY2599666 (Part B)
LY2599666 given SC once weekly for 12 weeks (13 doses).
Intervention: LY2599666
Outcomes
Primary Outcomes
Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration
Time Frame: Baseline through 4 weeks (Part A) or 16 weeks (Part B )
Number of participants who experienced one or more treatment-emergent serious adverse events related to study treatment. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Secondary Outcomes
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A(Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A))
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part B(Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part B))
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A(Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A))
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 168 Hours (AUC 0-168) of LY2599666 Part B(Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168 hours post-dose (Part B))
- Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A(Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A))
- Plasma Amyloid Beta (Aβ1-40 and Aβ1-42) Concentration Part B(Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part B))