A Study of LY3202626 in Healthy Participants and Participants With Alzheimer's Disease

Eli Lilly and Company94 enrolled

Overview

This study involves single and multiple doses of LY3202626 and will evaluate the effects of LY3202626 on the body. There will be 4 parts to this study. In Parts A and B, single increasing doses of LY3202626 will be given in capsule form. Part A will also include itraconazole given orally as a solution. Part A will last approximately 8-12 weeks. Part B will last approximately 5-6 weeks. In Parts C and D, participants will be dosed multiple days with the study drug. Part C will last approximately 11-14 weeks. Part D will last approximately 11-14 weeks and participants must have Alzheimer's Disease. Participants may only enroll in one part.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Healthy Volunteers Alzheimer Disease

Interventions

Eligibility

Sex: ALLMin age: 20 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * For Parts A, B, and C, are overtly healthy males or females (nonchildbearing potential), as determined by medical history and physical examination * Have a body mass index (BMI) of 18 to 32 kilograms per square meter (kg/m\^2) * For Part D, present with Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild to moderate AD * Have venous access sufficient to allow for blood sampling * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures and research unit policies Exclusion Criteria: * Taking over-the-counter or prescription medication with the exception of vitamins or minerals * Smoke more than 10 cigarettes per day * Are unwilling or unable to refrain from eating any food or drinking any beverage containing grapefruit or grapefruit juice for at least 2 weeks prior to first dose until completion of the study

Outcomes

Primary Outcomes

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

A summary of other nonserious Adverse Events (AE's), and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Time frame: Baseline to Study Completion (up to 14 weeks)

Secondary Outcomes

Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626

Summary of PK parameters of LY3202626 in plasma following oral administration of single doses for Parts A and B and multiple doses for Part C.

Time frame: Part A and B Day 1:Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; Part C Day 1:Predose, 0.5,1, 2, 4, 6, 8, and 12 hours postdose; Part C Day 14:Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours postdose

PK: Area Under the Concentration Time Curve (AUC) of LY3202626

Pharmacokinetic parameters for Part A and B were assessed on Day 1 using AUC 0-infinity (AUC0-inf). Pharmacokinetic parameters for Part C were assessed on Day 1 using AUC zero to time to last (AUC0-tlast), Day 14 using AUC steady state.

Time frame: Part A and B Day 1: Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; Part C Day 1:Presdose, 0.5,1, 2, 4, 6, 8,12 hours postdose; Day 14: Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours postdose

Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration

Plasma minimum A-beta 1-40 concentration or nadir concentration (Cnadir) is defined as the lowest concentration of plasma A-beta 1-40 following dose administration.

Time frame: Part A Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 postdose; Part C Day 14: Predose 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 120, 168, and 216 postdose

PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration

CSF minimum A-beta 1-40 concentration or nadir concentration (Cnadir) is defined as the lowest concentration of CSF A-beta 1-40 following dose administration.

Time frame: Part B: -4, -2, Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, and 36 hours postdose

PK: CSF Concentration of LY3202626

Time frame: Part C: Day 15 at 24 hours +/- 4 hours (hr) postdose

PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration

CSF Aβ1-40 change from baseline at Day 15 endpoint, 24 hours postdose (+/- 4 hours) following multiple doses of LY3202626.

Time frame: Parts C: Baseline, Day 15