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

Phase 1

Terminated

Conditions: Healthy
Alzheimer's Disease
Mild Cognitive Impairment

Interventions: Drug: LY2599666
Drug: Placebo SC
Drug: Placebo IV
Drug: Solanezumab

Registration Number: NCT02614131

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 50

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LY2599666 (Part A)	LY2599666	LY2599666 given subcutaneously (SC) once.
Placebo (Part A)	Placebo SC	Placebo matching LY2599666 given SC once.
LY2599666 (Part B)	LY2599666	LY2599666 given SC once weekly for 12 weeks (13 doses).
Placebo (Part B)	Placebo SC	Placebo given SC once weekly for 12 weeks (13 doses).
Placebo (Part C)	Placebo IV	Placebo given IV once weekly or once every 4 weeks for 12 weeks.
Solanezumab (Part C)	Solanezumab	Solanezumab given intravenously (IV) once weekly or once every 4 weeks for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration	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 Outcome Measures

Name	Time	Method
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)	PK: Cmax of LY2599666 after a single dose administered subcutaneously.
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)	PK: Cmax of LY2599666 after multiple doses administered subcutaneously.
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)	Area Under the Concentration versus Time Curve of zero to infinity (0 to ∞) after a single dose of LY2599666 administered subcutaneously.
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)	Area Under the Concentration time versus curve from 0-168 hours after weekly dose of LY2599666 administered subcutaneously.
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)	Concentration of plasma amyloid beta 1-40 in healthy participants after single dose of LY2599666 administered subcutaneously.
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)	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.

Trial Locations

Locations (4): Parexel Early Phase Unit at Glendale
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Glendale, California, United States
CRI Lifetree
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Marlton, New Jersey, United States
PRA Health Sciences
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Salt Lake City, Utah, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
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Shinjuku-Ku, Japan