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

Phase 1

Completed

Conditions: Alzheimer Disease
Healthy Volunteers

Interventions: Drug: LY3202626
Drug: Placebo (Part A, B, C)
Drug: Itraconazole

Registration Number: NCT02323334

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 94

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part A Cohort 1 Sequence1: 0.1mg, 1.6mg, Placcebo; 15mg	Placebo (Part A, B, C)	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.
Part A Cohort 1 Sequence 2: 0.1mg, PBO, 15mg, 15mg	Placebo (Part A, B, C)	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.
Part A Cohort 2 Sequence 1:0.4mg, 5mg, PBO, 0.4mg/Itraconazole	Placebo (Part A, B, C)	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.
Part A Cohort 2 Sequence 2: 0.4mg, PBO, 45mg. 0.4mg/Itra	Placebo (Part A, B, C)	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.
Part B Cohort 5: 10mg	LY3202626	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.
Part A Cohort 1 Sequence1: 0.1mg, 1.6mg, Placcebo; 15mg	LY3202626	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.
Part A Cohort 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra	Placebo (Part A, B, C)	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.
Part A Cohort 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra	Itraconazole	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.
Part C Cohort 7, 8 ,9: Placebo Comparator	Placebo (Part A, B, C)	Part C Cohort 7,8,9 involved healthy participants and was comprised of one period. Placebo given PO once daily for 14 days.
Part A Cohort 1 Sequence 3: PBO, 1.6mg, 15mg, Placebo	Placebo (Part A, B, C)	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.
Part A Cohort 3 Sequence 1: Food Effect Fed/Fasted	LY3202626	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.
Part B Cohort 4: 1.6mg	LY3202626	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.
Part B Cohort 4, 5, 6: Placebo Comparator	Placebo (Part A, B, C)	Part B Cohort 4,5,6 involved healthy participants and was comprised of one period. Single dose of PBO given PO in Period 1.
Part A Cohort 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra	LY3202626	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.
Part C Cohort 9: 26mg	LY3202626	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.
Part A Cohort 1 Sequence 2: 0.1mg, PBO, 15mg, 15mg	LY3202626	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.
Part A Cohort 1 Sequence 3: PBO, 1.6mg, 15mg, Placebo	LY3202626	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.
Part A Cohort 2 Sequence 1:0.4mg, 5mg, PBO, 0.4mg/Itraconazole	LY3202626	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.
Part A Cohort 2 Sequence 2: 0.4mg, PBO, 45mg. 0.4mg/Itra	LY3202626	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.
Part A Cohort 3 Sequence 2: Food Effect Fasted/Fed	LY3202626	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.
Part B Cohort 6: 26mg	LY3202626	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.
Part C Cohort 7: 1mg	LY3202626	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.
Part C Cohort 8: 6mg	LY3202626	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.
Part D Cohort 10: 6mg	LY3202626	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.
Part A Cohort 2 Sequence 2: 0.4mg, PBO, 45mg. 0.4mg/Itra	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, PBO Period 3: 45mg LY3202626 Period 4: 0.4mg LY3202626/200mg Itraconazole.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Baseline to Study Completion (up to 14 weeks)	A summary of other nonserious Adverse Events (AE's), and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Secondary Outcome Measures

Name	Time	Method
PK: Area Under the Concentration Time Curve (AUC) of LY3202626	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	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.
PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration	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	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.
Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626	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	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.
PK: CSF Concentration of LY3202626	Part C: Day 15 at 24 hours +/- 4 hours (hr) postdose
Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration	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	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.
PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration	Parts C: Baseline, Day 15	CSF Aβ1-40 change from baseline at Day 15 endpoint, 24 hours postdose (+/- 4 hours) following multiple doses of LY3202626.