A Study of LY2599666 in Healthy Participants and Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD)

Study 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.

Official Title
-----------------
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

Conditions
-----------------
Healthy, Alzheimer's Disease, Mild Cognitive Impairment

Intervention / Treatment
-----------------
* Drug: LY2599666
* Drug: Solanezumab
* Drug: Placebo SC
* Drug: Placebo IV


Participation Criteria
=================
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 Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) [Part C] Have had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen post treatment

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2599666 (Part A)<br>LY2599666 given subcutaneously (SC) once. | Drug: LY2599666<br>* Administered SC<br>|
| Placebo Comparator: Placebo (Part A)<br>Placebo matching LY2599666 given SC once. | Drug: Placebo SC<br>* Administered SC<br>|
| Experimental: LY2599666 (Part B)<br>LY2599666 given SC once weekly for 12 weeks (13 doses). | Drug: LY2599666<br>* Administered SC<br>|
| Placebo Comparator: Placebo (Part B)<br>Placebo given SC once weekly for 12 weeks (13 doses). | Drug: Placebo SC<br>* Administered SC<br>|
| Experimental: Solanezumab (Part C)<br>Solanezumab given intravenously (IV) once weekly or once every 4 weeks for 12 weeks. | Drug: Solanezumab<br>* Administered IV<br>* Other names: LY2062430;|
| Placebo Comparator: Placebo (Part C)<br>Placebo given IV once weekly or once every 4 weeks for 12 weeks. | Drug: Placebo IV<br>* Administered IV<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | 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. | Baseline through 4 weeks (Part A) or 16 weeks (Part B ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A | PK: Cmax of LY2599666 after a single dose administered subcutaneously. | 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 | PK: Cmax of LY2599666 after multiple doses administered subcutaneously. | 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 | Area Under the Concentration versus Time Curve of zero to infinity (0 to ∞) after a single dose of LY2599666 administered subcutaneously. | 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 | Area Under the Concentration time versus curve from 0-168 hours after weekly dose of LY2599666 administered subcutaneously. | 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 | Concentration of plasma amyloid beta 1-40 in healthy participants after single dose of LY2599666 administered subcutaneously. | 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 | Concentration of plasma amyloid beta 1-40 and 1-42, in participants with Mild Cognitive Impairment (MCI) or Alzheimer Disease, after multiple doses of LY2599666 administered subcutaneously. | 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) |