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

Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY3202626

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 Overview

• Status: Completed
• Conditions: Alzheimer Disease; Healthy Volunteers
• Intervention / Treatment: Drug: LY3202626; Drug: Placebo (Part A, B, C); Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

17

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part A Cohort 1 Sequence1: 0.1mg, 1.6mg, Placcebo; 15mg; Part A Cohort 1 involved healthy participants and was comprised of 4 treatment periods with a washout period of approximately 14 days between doses. Period 1: 0.1mg LY3202626 Period 2: 1.6mg LY3202626 Period 3: 15 mg placebo (PBO) Period 4: 15mg LY3202626.	Drug: LY3202626; administered orally; Drug: Placebo (Part A, B, C); administered orally
Experimental: Part A Cohort 1 Sequence 2: 0.1mg, PBO, 15mg, 15mg; Part A Cohort 1 involved healthy participants and comprised of 4 treatment periods with a washout period of approximately 14 days between doses. Period 1: 0.1mg Period 2: PBO Period 3: 15mg LY3202626 Period 4: 15mg LY3202626.	Drug: LY3202626; administered orally; Drug: Placebo (Part A, B, C); administered orally
Experimental: Part A Cohort 1 Sequence 3: PBO, 1.6mg, 15mg, Placebo; Part A Cohort 1 involved healthy participants and comprised of 4 treatment periods with a washout period of approximately 14 days between doses. Period 1: PBO Period 2: 1.6mg LY3202626 Period 3: 15mg LY3202626 Period 4: PBO.	Drug: LY3202626; administered orally; Drug: Placebo (Part A, B, C); administered orally
Experimental: Part A Cohort 2 Sequence 1:0.4mg, 5mg, PBO, 0.4mg/Itraconazole; Part A Cohort 2 involved healthy participants and comprised of 4 treatment periods with a washout period of approximately 14 days between doses. Period 1: 0.4mg LY3202626 Period 2: 5mg LY3202626 Period 3: 45mg, PBO Period 4: 0.4mg LY3202626/200mg Itraconazole.	Drug: LY3202626; administered orally; Drug: Placebo (Part A, B, C); administered orally
Experimental: Part A Cohort 2 Sequence 2: 0.4mg, PBO, 45mg. 0.4mg/Itra; Part A Cohort 2 involved healthy participants and comprised of 4 treatment periods with a washout period of approximately 14 days between doses. Period 1: 0.4mg LY3202626 Period 2: 5mg, PBO Period 3: 45mg LY3202626 Period 4: 0.4mg LY3202626/200mg Itraconazole.	Drug: LY3202626; administered orally; Drug: Placebo (Part A, B, C); administered orally; Drug: Itraconazole; administered orally
Experimental: Part A Cohort 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra; Part A Cohort 2 involved healthy participants and was comprised of 4 treatment periods with a washout period of approximately 14 days between doses. Period 1: 0.4mg, PBO Period 2: 5mg LY3202626 Period 3: 45mg LY3202626 Period 4: 0.4mg LY3202626/200mg Itraconazole.	Drug: LY3202626; administered orally; Drug: Placebo (Part A, B, C); administered orally; Drug: Itraconazole; administered orally
Experimental: Part A Cohort 3 Sequence 1: Food Effect Fed/Fasted; Part A Cohort 3 involved healthy participants and was comprised of two treatment periods with a washout period of approximately 14 days between doses. Single dose of 10mg LY3202626 given PO in Period 1 and 2. Period 1: Fed 2: Fasted.	Drug: LY3202626; administered orally
Experimental: Part A Cohort 3 Sequence 2: Food Effect Fasted/Fed; Part A Cohort 3 involved healthy participants and was comprised of two treatment periods with a washout period of approximately 14 days between doses. Single dose 10mg LY3202626 given PO in Period 1 and 2. Period 1: Fasted 2: Fed.	Drug: LY3202626; administered orally
Experimental: Part B Cohort 4: 1.6mg; Part B Cohort 4 involved healthy participants and was comprised of one period. Single dose of 1.6mg LY3202626 given PO in Period 1. Dose determined by Part A.	Drug: LY3202626; administered orally
Experimental: Part B Cohort 5: 10mg; Part B Cohort 5 involved healthy participants and was comprised of one period. Single dose of 10mg LY3202626 given PO in Period 1. Dose determined by Part A.	Drug: LY3202626; administered orally
Experimental: Part B Cohort 6: 26mg; Part B Cohort 6 involved healthy participants and was comprised of one period. Single dose of 26mg LY3202626 given PO in Period 1. Dose determined by Part A.	Drug: LY3202626; administered orally
Placebo Comparator: Part B Cohort 4, 5, 6: Placebo Comparator; Part B Cohort 4,5,6 involved healthy participants and was comprised of one period. Single dose of PBO given PO in Period 1.	Drug: Placebo (Part A, B, C); administered orally
Experimental: Part C Cohort 7: 1mg; Part C Cohort 7 involved healthy participants and was comprised of one period. 1mg LY3202626 given PO once daily for 14 days. Dose determined by Part B.	Drug: LY3202626; administered orally
Experimental: Part C Cohort 8: 6mg; Part C Cohort 8 involved healthy participants and was comprised of one period. 6mg LY3202626 was given PO once daily for 14 days. Dose determined by Part B.	Drug: LY3202626; administered orally
Experimental: Part C Cohort 9: 26mg; Part C Cohort 9 included healthy participants and was comprised of one period. 26mg LY3202626 was given PO once daily for 14 days. Dose determined by Part B.	Drug: LY3202626; administered orally
Placebo Comparator: Part C Cohort 7, 8 ,9: Placebo Comparator; Part C Cohort 7,8,9 involved healthy participants and was comprised of one period. Placebo given PO once daily for 14 days.	Drug: Placebo (Part A, B, C); administered orally
Experimental: Part D Cohort 10: 6mg; Part D Cohort 10 involved participants with Alzheimer's disease and was comprised of one period. 6mg LY3202626 was given PO once daily for 14 days. Dose determined by Part B.	Drug: LY3202626; administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Study Completion (up to 14 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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		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.	Parts C: Baseline, Day 15

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: December 8, 2014
• First Submitted That Met QC Criteria: December 17, 2014
• First Posted (Estimate): December 23, 2014

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 15562 (Stanford University Research Compliance Office); I7X-EW-LLCA (Other Identifier: Eli Lilly and Company)