Trial Outcomes & Findings for A Study of LY3202626 in Healthy Participants and Participants With Alzheimer's Disease (NCT NCT02323334)

Last Updated: 2021-04-19

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

94 participants

Primary outcome timeframe

Baseline to Study Completion (up to 14 weeks)

Results posted on

2021-04-19

Participant Flow

Participant milestones

Participant milestones
Measure	Part A Cohort 1 Sequence 1: 0.1mg, 1.6mg, Placebo (PBO); 15mg Part A Cohort 1 involved healthy participants and was comprised of 4 treatment periods. There was a washout period of approximately 14 days between doses. Period 1: 0.1mg LY3202626 Period 2: 1.6mg LY3202626 Period 3: 15 mg PBO Period 4: 15mg LY3202626	Part A Cohort 1 Sequence 2: 1.6mg, PBO,15mg, 15mg Part A Cohort 1 involved healthy participants and was comprised of 4 treatment periods. There was a washout period of approximately 14 days between doses. Period 1: 1.6mg LY3202626 Period 2: PBO Period 3: 15mg LY3202626 Period 4: 15mg LY3202626	Part A Cohort 1 Sequence 3: PBO, 1.6mg, 15mg, PBO Part A Cohort 1 involved healthy participants and was comprised of 4 treatment periods. There was 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/200mg Itra Part A Cohort 2 involved healthy participants and was comprised of 4 treatment periods. Period 4 includes 0.4mg LY3202626 and 200mg Itraconazole (Itra). There was 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/200mg Itra Part A Cohort 2 involved healthy participants and was comprised of 4 treatment periods. Period 4 includes 0.4mg LY3202626 and 200mg Itraconazole.There was 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 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra Part A Cohort 2 involved healthy participants and was comprised of 4 treatment periods. Period 4 includes 0.4mg LY3202626 and 200mg Itraconazole. There was 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 3 Sequence 1: Food Effect Fed/Fasted Part A Cohort 3 involved healthy participants and was comprised of two treatment periods. Single dose of 10mg LY3202626 given PO in Period 1 and 2. There was a washout period of approximately 14 days between doses. Period 1: Fed Period 2: Fasted	Part A Cohort 3 Sequence 2: Food Effect Fasted/Fed Part A Cohort 3 involved healthy participants and was comprised of two treatment periods. Single dose 10mg LY3202626 given PO in Period 1 and 2. There was a washout period of approximately 14 days between doses. Period 1: Fasted Period 2: Fed	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.	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.	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.	Part B Cohort 4, 5, 6: PBO 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.	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.	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.	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.	Part C Cohort 7, 8 ,9: PBO Comparator Part C Cohort 7, 8, 9 involved healthy participants and was comprised of one period. PBO given PO once daily for 14 days.	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.
Period 1 STARTED	4	4	4	4	4	4	6	6	5	7	5	3	9	9	9	9	2
Period 1 Received at Least One Dose of Study Drug	4	4	4	4	4	4	6	6	5	7	5	3	9	9	9	9	2
Period 1 COMPLETED	4	4	4	4	4	4	6	6	5	7	5	3	9	9	9	9	2
Period 1 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 2 STARTED	4	4	4	4	4	4	6	6	0	0	0	0	0	0	0	0	0
Period 2 COMPLETED	4	4	4	4	4	4	6	6	0	0	0	0	0	0	0	0	0
Period 2 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 3 STARTED	4	4	4	4	4	4	0	0	0	0	0	0	0	0	0	0	0
Period 3 COMPLETED	3	4	3	4	4	4	0	0	0	0	0	0	0	0	0	0	0
Period 3 NOT COMPLETED	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 4 STARTED	3	4	3	4	4	4	0	0	0	0	0	0	0	0	0	0	0
Period 4 COMPLETED	3	4	3	4	4	4	0	0	0	0	0	0	0	0	0	0	0
Period 4 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A Cohort 1 Sequence 1: 0.1mg, 1.6mg, Placebo (PBO); 15mg Part A Cohort 1 involved healthy participants and was comprised of 4 treatment periods. There was a washout period of approximately 14 days between doses. Period 1: 0.1mg LY3202626 Period 2: 1.6mg LY3202626 Period 3: 15 mg PBO Period 4: 15mg LY3202626	Part A Cohort 1 Sequence 2: 1.6mg, PBO,15mg, 15mg Part A Cohort 1 involved healthy participants and was comprised of 4 treatment periods. There was a washout period of approximately 14 days between doses. Period 1: 1.6mg LY3202626 Period 2: PBO Period 3: 15mg LY3202626 Period 4: 15mg LY3202626	Part A Cohort 1 Sequence 3: PBO, 1.6mg, 15mg, PBO Part A Cohort 1 involved healthy participants and was comprised of 4 treatment periods. There was 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/200mg Itra Part A Cohort 2 involved healthy participants and was comprised of 4 treatment periods. Period 4 includes 0.4mg LY3202626 and 200mg Itraconazole (Itra). There was 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/200mg Itra Part A Cohort 2 involved healthy participants and was comprised of 4 treatment periods. Period 4 includes 0.4mg LY3202626 and 200mg Itraconazole.There was 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 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra Part A Cohort 2 involved healthy participants and was comprised of 4 treatment periods. Period 4 includes 0.4mg LY3202626 and 200mg Itraconazole. There was 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 3 Sequence 1: Food Effect Fed/Fasted Part A Cohort 3 involved healthy participants and was comprised of two treatment periods. Single dose of 10mg LY3202626 given PO in Period 1 and 2. There was a washout period of approximately 14 days between doses. Period 1: Fed Period 2: Fasted	Part A Cohort 3 Sequence 2: Food Effect Fasted/Fed Part A Cohort 3 involved healthy participants and was comprised of two treatment periods. Single dose 10mg LY3202626 given PO in Period 1 and 2. There was a washout period of approximately 14 days between doses. Period 1: Fasted Period 2: Fed	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.	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.	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.	Part B Cohort 4, 5, 6: PBO 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.	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.	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.	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.	Part C Cohort 7, 8 ,9: PBO Comparator Part C Cohort 7, 8, 9 involved healthy participants and was comprised of one period. PBO given PO once daily for 14 days.	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.
Period 3 Lost to Follow-up	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 3 Withdrawal by Subject	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A Cohort 1 n=12 Participants Escalating single dose given orally (PO)per randomly assigned treatment sequence of 0.1mg, 1.6mg, 15mg LY3202626 or placebo.	Part A Cohort 2 n=12 Participants Escalating single dose given PO per randomly assigned treatment sequence of 0.4mg, 5mg, or 45mg LY3202626, placebo. Some participants may also receive multiple doses of 200 mg of Itraconazole PO in 1 period with 0.4mg of LY3202626.	Part A Food Effect Cohort 3 n=12 Participants Single dose of 10mg LY3202626 given PO in Period 1 and Period 2 only.	Part B Cohort 4 n=6 Participants Single oral dose of 1.6mg LY3202626 or placebo given PO in Period 1. Dose determined by Part A.	Part B Cohort 5 n=8 Participants Single oral dose of 10mg LY3202626 or placebo given PO in in Period 1. Dose determined by Part A.	Part B Cohort 6 n=6 Participants Single oral dose of 26mg LY3202626 or placebo given PO in Period 1. Dose determined by Part A.	Part C Cohort 7 n=12 Participants Multiple oral doses of 1mg LY3202626 given PO once daily for 14 days. Dose determined by Part B.	Part C Cohort 8 n=12 Participants Multiple oral doses of 6mg LY3202626 given PO once daily for 14 days. Dose determined by Part B.	Part C Cohort 9 n=12 Participants Multiple oral doses of 26mg LY3202626 given PO once daily for 14 days. Dose determined by Part B.	Part D Cohort 10 n=2 Participants Multiple oral doses of 6mg LY3202626 given PO once daily for 14 days. Dose determined by Part B.	Total n=94 Participants Total of all reporting groups
Age, Continuous	33.0 years STANDARD_DEVIATION 8.1 • n=5 Participants	36.9 years STANDARD_DEVIATION 8.4 • n=7 Participants	39.0 years STANDARD_DEVIATION 13.6 • n=5 Participants	36.5 years STANDARD_DEVIATION 12.4 • n=4 Participants	43.0 years STANDARD_DEVIATION 11.3 • n=21 Participants	35.2 years STANDARD_DEVIATION 7.2 • n=10 Participants	37.5 years STANDARD_DEVIATION 10.5 • n=115 Participants	40.4 years STANDARD_DEVIATION 8.1 • n=24 Participants	40.5 years STANDARD_DEVIATION 10.5 • n=42 Participants	68.0 years STANDARD_DEVIATION 2.8 • n=42 Participants	38.70 years STANDARD_DEVIATION 10.93 • n=42 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	2 Participants n=42 Participants	10 Participants n=42 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	8 Participants n=21 Participants	6 Participants n=10 Participants	12 Participants n=115 Participants	11 Participants n=24 Participants	11 Participants n=42 Participants	0 Participants n=42 Participants	84 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=10 Participants	2 Participants n=115 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	0 Participants n=42 Participants	18 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	11 Participants n=7 Participants	9 Participants n=5 Participants	6 Participants n=4 Participants	7 Participants n=21 Participants	3 Participants n=10 Participants	10 Participants n=115 Participants	9 Participants n=24 Participants	9 Participants n=42 Participants	2 Participants n=42 Participants	76 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	4 Participants n=115 Participants	4 Participants n=24 Participants	4 Participants n=42 Participants	2 Participants n=42 Participants	30 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	3 Participants n=115 Participants	3 Participants n=24 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	18 Participants n=42 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	7 Participants n=21 Participants	5 Participants n=10 Participants	4 Participants n=115 Participants	5 Participants n=24 Participants	7 Participants n=42 Participants	0 Participants n=42 Participants	44 Participants n=42 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	6 participants n=4 Participants	8 participants n=21 Participants	6 participants n=10 Participants	12 participants n=115 Participants	12 participants n=24 Participants	12 participants n=42 Participants	2 participants n=42 Participants	94 participants n=42 Participants

PRIMARY outcome

Timeframe: Baseline to Study Completion (up to 14 weeks)

Population: All participants who received at least one dose of study drug.

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

Outcome measures

Outcome measures
Measure	Part A, B, and C Placebo (PBO) n=36 Participants Single dose placebo given PO in Part A and B. Multiple doses of PBO given PO in Part C.	Part A 0.1mg LY3202626 n=8 Participants Single dose of 0.1mg LY3202626 given PO Period 1 Cohort 1.	Part A 0.4mg LY3202626 n=8 Participants Single dose of 0.4mg LY3202626 given PO in Period 1 Cohort 2.	Part A 0.4mg LY3202626 + 200mg Itraconazole n=12 Participants Single dose of 0.4mg LY3202626 +200mg Itraconazole given PO in Period 4 Cohort 2.	Part C 1mg LY3202626 QD n=9 Participants Multiple daily dose of 1mg LY3202626 given PO once daily for 14 days.	Part A and B 1.6mg LY3202626 n=13 Participants Single dose of 1.6mg LY3202626 given PO in Period 2 Cohort 1 in Part A and Period 1 Part B.	Part A 5mg LY3202626 n=8 Participants Single dose of 5mg LY3202626 given PO in in Period 2 Cohort 2.	Part C and D 6mg LY3202626 QD n=11 Participants Multiple daily dose of 6mg LY3202626 given PO once daily for 14 days.	Part A, B and C 10mg LY3202626 n=19 Participants Single dose of 10mg LY3202626 given PO in Part A and B. Multiple dose of 10mg LY3202626 given PO in Part C once daily for 14 days.	Part A 15mg LY3202626 n=11 Participants Single dose of 15mg LY3202626 given PO in Period 3 Cohort 1.	Part B and C 26mg LY3202626 n=14 Participants Single dose of 26mg LY3202626 given PO in Period 1 in Part B. Multiple daily dose of 26mg LY3202626 given PO once daily for 14 days in Part C.	Part A 45mg LY3202626 n=8 Participants Single dose of 45mg LY3202626 given PO in in Period 3 Cohort 2.
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Population: All participants in Part A, B, and C who received at least one dose of study drug and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	Part A, B, and C Placebo (PBO) n=3 Participants Single dose placebo given PO in Part A and B. Multiple doses of PBO given PO in Part C.	Part A 0.1mg LY3202626 n=8 Participants Single dose of 0.1mg LY3202626 given PO Period 1 Cohort 1.	Part A 0.4mg LY3202626 n=8 Participants Single dose of 0.4mg LY3202626 given PO in Period 1 Cohort 2.	Part A 0.4mg LY3202626 + 200mg Itraconazole n=8 Participants Single dose of 0.4mg LY3202626 +200mg Itraconazole given PO in Period 4 Cohort 2.	Part C 1mg LY3202626 QD n=8 Participants Multiple daily dose of 1mg LY3202626 given PO once daily for 14 days.	Part A and B 1.6mg LY3202626 n=8 Participants Single dose of 1.6mg LY3202626 given PO in Period 2 Cohort 1 in Part A and Period 1 Part B.	Part A 5mg LY3202626 n=5 Participants Single dose of 5mg LY3202626 given PO in in Period 2 Cohort 2.	Part C and D 6mg LY3202626 QD n=7 Participants Multiple daily dose of 6mg LY3202626 given PO once daily for 14 days.	Part A, B and C 10mg LY3202626 n=5 Participants Single dose of 10mg LY3202626 given PO in Part A and B. Multiple dose of 10mg LY3202626 given PO in Part C once daily for 14 days.	Part A 15mg LY3202626 n=8 Participants Single dose of 15mg LY3202626 given PO in Period 3 Cohort 1.	Part B and C 26mg LY3202626 n=9 Participants Single dose of 26mg LY3202626 given PO in Period 1 in Part B. Multiple daily dose of 26mg LY3202626 given PO once daily for 14 days in Part C.	Part A 45mg LY3202626 n=9 Participants Single dose of 45mg LY3202626 given PO in in Period 3 Cohort 2.
Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626	0.169 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 50	0.486 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 81	2.89 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 70	7.91 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 56	21.3 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 77	92.5 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 47	2.90 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 86	3.75 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 176	36.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 126	2.57 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 2.5	11.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 71	72.8 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 61

SECONDARY outcome

Timeframe: 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

Population: All participants in Parts A, B, and C who received at least one dose of study drug and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	Part A, B, and C Placebo (PBO) n=3 Participants Single dose placebo given PO in Part A and B. Multiple doses of PBO given PO in Part C.	Part A 0.1mg LY3202626 n=8 Participants Single dose of 0.1mg LY3202626 given PO Period 1 Cohort 1.	Part A 0.4mg LY3202626 n=8 Participants Single dose of 0.4mg LY3202626 given PO in Period 1 Cohort 2.	Part A 0.4mg LY3202626 + 200mg Itraconazole n=8 Participants Single dose of 0.4mg LY3202626 +200mg Itraconazole given PO in Period 4 Cohort 2.	Part C 1mg LY3202626 QD n=8 Participants Multiple daily dose of 1mg LY3202626 given PO once daily for 14 days.	Part A and B 1.6mg LY3202626 n=8 Participants Single dose of 1.6mg LY3202626 given PO in Period 2 Cohort 1 in Part A and Period 1 Part B.	Part A 5mg LY3202626 n=5 Participants Single dose of 5mg LY3202626 given PO in in Period 2 Cohort 2.	Part C and D 6mg LY3202626 QD n=7 Participants Multiple daily dose of 6mg LY3202626 given PO once daily for 14 days.	Part A, B and C 10mg LY3202626 n=5 Participants Single dose of 10mg LY3202626 given PO in Part A and B. Multiple dose of 10mg LY3202626 given PO in Part C once daily for 14 days.	Part A 15mg LY3202626 n=8 Participants Single dose of 15mg LY3202626 given PO in Period 3 Cohort 1.	Part B and C 26mg LY3202626 n=9 Participants Single dose of 26mg LY3202626 given PO in Period 1 in Part B. Multiple daily dose of 26mg LY3202626 given PO once daily for 14 days in Part C.	Part A 45mg LY3202626 n=9 Participants Single dose of 45mg LY3202626 given PO in in Period 3 Cohort 2.
PK: Area Under the Concentration Time Curve (AUC) of LY3202626	NA nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation NA At doses less than 1.6 mg, the AUC(0-∞) could not be reliably quantified.	NA nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation NA At doses less than 1.6 mg, the AUC(0-∞) could not be reliably quantified.	60.6 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 49	197 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 38	393 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 84	1680 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 34	49.9 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 41	102 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 111	575 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 62	38.6 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 25	151 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 54	1020 nanogram x hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 50

SECONDARY outcome

Timeframe: 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

Population: All participants in Part A, Periods 1-3 and Part C, Period 3, who received at least one dose of study drug and had evaluable PD data analyzed per protocol. Participants in Part B and D were not assessed per protocol.

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.

Outcome measures

Outcome measures
Measure	Part A, B, and C Placebo (PBO) n=24 Participants Single dose placebo given PO in Part A and B. Multiple doses of PBO given PO in Part C.	Part A 0.1mg LY3202626 n=8 Participants Single dose of 0.1mg LY3202626 given PO Period 1 Cohort 1.	Part A 0.4mg LY3202626 n=8 Participants Single dose of 0.4mg LY3202626 given PO in Period 1 Cohort 2.	Part A 0.4mg LY3202626 + 200mg Itraconazole n=8 Participants Single dose of 0.4mg LY3202626 +200mg Itraconazole given PO in Period 4 Cohort 2.	Part C 1mg LY3202626 QD n=8 Participants Multiple daily dose of 1mg LY3202626 given PO once daily for 14 days.	Part A and B 1.6mg LY3202626 n=8 Participants Single dose of 1.6mg LY3202626 given PO in Period 2 Cohort 1 in Part A and Period 1 Part B.	Part A 5mg LY3202626 n=8 Participants Single dose of 5mg LY3202626 given PO in in Period 2 Cohort 2.	Part C and D 6mg LY3202626 QD n=9 Participants Multiple daily dose of 6mg LY3202626 given PO once daily for 14 days.	Part A, B and C 10mg LY3202626 n=9 Participants Single dose of 10mg LY3202626 given PO in Part A and B. Multiple dose of 10mg LY3202626 given PO in Part C once daily for 14 days.	Part A 15mg LY3202626 n=9 Participants Single dose of 15mg LY3202626 given PO in Period 3 Cohort 1.	Part B and C 26mg LY3202626 n=9 Participants Single dose of 26mg LY3202626 given PO in Period 1 in Part B. Multiple daily dose of 26mg LY3202626 given PO once daily for 14 days in Part C.	Part A 45mg LY3202626 Single dose of 45mg LY3202626 given PO in in Period 3 Cohort 2.
Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration	107 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 35.1	58.1 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 150	61.8 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 25.6	33.4 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 62.0	25.2 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 16.8	17.0 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 33.6	7.93 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 42.0	84.6 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 26.5	24.0 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 33.1	5.80 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 51.9	4.2 Picogram per milliliter (pg/mL) Geometric Coefficient of Variation 0	—

SECONDARY outcome

Timeframe: 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

Population: All participants in Part B who received at least one dose of study drug and had evaluable CSF PD data analyzed per protocol. Participants in Part A, C and D were not assessed per protocol.

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.

Outcome measures

Outcome measures
Measure	Part A, B, and C Placebo (PBO) n=3 Participants Single dose placebo given PO in Part A and B. Multiple doses of PBO given PO in Part C.	Part A 0.1mg LY3202626 n=5 Participants Single dose of 0.1mg LY3202626 given PO Period 1 Cohort 1.	Part A 0.4mg LY3202626 n=5 Participants Single dose of 0.4mg LY3202626 given PO in Period 1 Cohort 2.	Part A 0.4mg LY3202626 + 200mg Itraconazole n=5 Participants Single dose of 0.4mg LY3202626 +200mg Itraconazole given PO in Period 4 Cohort 2.	Part C 1mg LY3202626 QD Multiple daily dose of 1mg LY3202626 given PO once daily for 14 days.	Part A and B 1.6mg LY3202626 Single dose of 1.6mg LY3202626 given PO in Period 2 Cohort 1 in Part A and Period 1 Part B.	Part A 5mg LY3202626 Single dose of 5mg LY3202626 given PO in in Period 2 Cohort 2.	Part C and D 6mg LY3202626 QD Multiple daily dose of 6mg LY3202626 given PO once daily for 14 days.	Part A, B and C 10mg LY3202626 Single dose of 10mg LY3202626 given PO in Part A and B. Multiple dose of 10mg LY3202626 given PO in Part C once daily for 14 days.	Part A 15mg LY3202626 Single dose of 15mg LY3202626 given PO in Period 3 Cohort 1.	Part B and C 26mg LY3202626 Single dose of 26mg LY3202626 given PO in Period 1 in Part B. Multiple daily dose of 26mg LY3202626 given PO once daily for 14 days in Part C.	Part A 45mg LY3202626 Single dose of 45mg LY3202626 given PO in in Period 3 Cohort 2.
PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration	7980 pg/mL Geometric Coefficient of Variation 53.8	5700 pg/mL Geometric Coefficient of Variation 22.3	5770 pg/mL Geometric Coefficient of Variation 41.8	2980 pg/mL Geometric Coefficient of Variation 46.4	—	—	—	—	—	—	—	—

SECONDARY outcome

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

Population: All participants in Part C who received at least one dose of study drug and had evaluable CSF PK data per protocol. Participants in Part A, B and D were not assessed per protocol.

Outcome measures

Outcome measures
Measure	Part A, B, and C Placebo (PBO) n=9 Participants Single dose placebo given PO in Part A and B. Multiple doses of PBO given PO in Part C.	Part A 0.1mg LY3202626 n=9 Participants Single dose of 0.1mg LY3202626 given PO Period 1 Cohort 1.	Part A 0.4mg LY3202626 n=9 Participants Single dose of 0.4mg LY3202626 given PO in Period 1 Cohort 2.	Part A 0.4mg LY3202626 + 200mg Itraconazole Single dose of 0.4mg LY3202626 +200mg Itraconazole given PO in Period 4 Cohort 2.	Part C 1mg LY3202626 QD Multiple daily dose of 1mg LY3202626 given PO once daily for 14 days.	Part A and B 1.6mg LY3202626 Single dose of 1.6mg LY3202626 given PO in Period 2 Cohort 1 in Part A and Period 1 Part B.	Part A 5mg LY3202626 Single dose of 5mg LY3202626 given PO in in Period 2 Cohort 2.	Part C and D 6mg LY3202626 QD Multiple daily dose of 6mg LY3202626 given PO once daily for 14 days.	Part A, B and C 10mg LY3202626 Single dose of 10mg LY3202626 given PO in Part A and B. Multiple dose of 10mg LY3202626 given PO in Part C once daily for 14 days.	Part A 15mg LY3202626 Single dose of 15mg LY3202626 given PO in Period 3 Cohort 1.	Part B and C 26mg LY3202626 Single dose of 26mg LY3202626 given PO in Period 1 in Part B. Multiple daily dose of 26mg LY3202626 given PO once daily for 14 days in Part C.	Part A 45mg LY3202626 Single dose of 45mg LY3202626 given PO in in Period 3 Cohort 2.
PK: CSF Concentration of LY3202626	0.0648 ng/mL Geometric Coefficient of Variation 46.2	0.202 ng/mL Geometric Coefficient of Variation 48.9	1.26 ng/mL Geometric Coefficient of Variation 44.8	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Parts C: Baseline, Day 15

Population: All participants in Part C who received at least one dose of study drug and had evaluable CSF PD data analyzed. Participants in Part A, B and D were not assessed per protocol.

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