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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

LY3202626

Placebo (Part A, B, C)

Itraconazole

About this trial

This is an interventional basic science trial for Healthy Volunteers

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

California Clinical Trials Medical Group

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm Type

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Part A Cohort 1 Sequence1: 0.1mg, 1.6mg, Placcebo; 15mg

Part A Cohort 1 Sequence 2: 0.1mg, PBO, 15mg, 15mg

Part A Cohort 1 Sequence 3: PBO, 1.6mg, 15mg, Placebo

Part A Cohort 2 Sequence 1:0.4mg, 5mg, PBO, 0.4mg/Itraconazole

Part A Cohort 2 Sequence 2: 0.4mg, PBO, 45mg. 0.4mg/Itra

Part A Cohort 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra

Part A Cohort 3 Sequence 1: Food Effect Fed/Fasted

Part A Cohort 3 Sequence 2: Food Effect Fasted/Fed

Part B Cohort 4: 1.6mg

Part B Cohort 5: 10mg

Part B Cohort 6: 26mg

Part B Cohort 4, 5, 6: Placebo Comparator

Part C Cohort 7: 1mg

Part C Cohort 8: 6mg

Part C Cohort 9: 26mg

Part C Cohort 7, 8 ,9: Placebo Comparator

Part D Cohort 10: 6mg

Arm Description

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 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 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 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 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 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 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 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 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 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 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 involved healthy participants and was comprised of one period. Single dose of PBO given PO in Period 1.

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 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 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 involved healthy participants and was comprised of one period. Placebo given PO once daily for 14 days.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

PK: CSF Concentration of LY3202626

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.

Full Information

NCT ID

NCT02323334

First Posted

December 8, 2014

Last Updated

March 22, 2021

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT02323334

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

December 2014 (undefined)

Primary Completion Date

February 2016 (Actual)

Study Completion Date

February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy Volunteers, Alzheimer Disease

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

94 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A Cohort 1 Sequence1: 0.1mg, 1.6mg, Placcebo; 15mg

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

Part A Cohort 1 Sequence 2: 0.1mg, PBO, 15mg, 15mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part A Cohort 1 Sequence 3: PBO, 1.6mg, 15mg, Placebo

Arm Type

Experimental

Arm Description

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.

Arm Title

Part A Cohort 2 Sequence 1:0.4mg, 5mg, PBO, 0.4mg/Itraconazole

Arm Type

Experimental

Arm Description

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.

Arm Title

Part A Cohort 2 Sequence 2: 0.4mg, PBO, 45mg. 0.4mg/Itra

Arm Type

Experimental

Arm Description

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.

Arm Title

Part A Cohort 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra

Arm Type

Experimental

Arm Description

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.

Arm Title

Part A Cohort 3 Sequence 1: Food Effect Fed/Fasted

Arm Type

Experimental

Arm Description

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.

Arm Title

Part A Cohort 3 Sequence 2: Food Effect Fasted/Fed

Arm Type

Experimental

Arm Description

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.

Arm Title

Part B Cohort 4: 1.6mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part B Cohort 5: 10mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part B Cohort 6: 26mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part B Cohort 4, 5, 6: Placebo Comparator

Arm Type

Placebo Comparator

Arm Description

Part B Cohort 4,5,6 involved healthy participants and was comprised of one period. Single dose of PBO given PO in Period 1.

Arm Title

Part C Cohort 7: 1mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part C Cohort 8: 6mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part C Cohort 9: 26mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part C Cohort 7, 8 ,9: Placebo Comparator

Arm Type

Placebo Comparator

Arm Description

Part C Cohort 7,8,9 involved healthy participants and was comprised of one period. Placebo given PO once daily for 14 days.

Arm Title

Part D Cohort 10: 6mg

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

LY3202626

Intervention Description

administered orally

Intervention Type

Drug

Intervention Name(s)

Placebo (Part A, B, C)

Intervention Description

administered orally

Intervention Type

Drug

Intervention Name(s)

Itraconazole

Intervention Description

administered orally

Primary Outcome Measure Information:

Title

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

Description

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 Outcome Measure Information:

Title

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

Description

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

Title

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

Description

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

Title

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

Description

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

Title

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

Description

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

Title

PK: CSF Concentration of LY3202626

Time Frame

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

Title

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

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

California Clinical Trials Medical Group

City

Glendale

State/Province

California

ZIP/Postal Code

91206

Country

United States

Healthy Volunteers, Alzheimer Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial