A Study of LY3323795 in Healthy Participants

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to investigate the safety of LY3323795 and the effects it has on the body. The study drug or placebo (sugar pill) will be given by mouth to healthy participants. The study has three parts. Each participant may only enroll in one part. The study will last 14 to 43 days, depending on the part. Screening must be completed prior to study start.

Official Title
-----------------
Single-Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3323795 in Healthy Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: LY3323795
* Drug: Itraconazole
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males or females of non-childbearing potential at time of screening Have a body mass index (BMI) between 18.0 kilograms per square meter (kg/m²) and 32.0 kg/m², inclusive Exclusion Criteria: Have participated, within the last 30 days, in a clinical trial involving an investigational product. Have a QT corrected for heart rate (QTc) (using Bazett's formula) interval value of greater than 450 millisecond (msec) (males) or greater than 470 msec (females)

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3323795 (Part A)<br>Participants received escalating doses of 0.3 mg (milligrams), 1 mg, 3 mg, 10 mg, 30 mg and 100 mg of LY3323795 orally. | Drug: LY3323795<br>* Administered orally<br>|
| Placebo Comparator: Placebo (Part A)<br>Participants received placebo identical to LY3323795 orally. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: LY3323795 (Part B)<br>Participants received 6 mg, 20 mg and 80 mg of LY3323795 orally. | Drug: LY3323795<br>* Administered orally<br>|
| Placebo Comparator: Placebo (Part B)<br>Participants received placebo identical to LY3323795 orally. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: LY3323795 (Part C)<br>Part C was not initiated due to a Lilly internal strategy decision. | Drug: LY3323795<br>* Administered orally<br>|
| Experimental: LY3323795 + Itraconazole (Part C)<br>Part C was not initiated due to a Lilly internal strategy decision. | Drug: LY3323795<br>* Administered orally<br>Drug: Itraconazole<br>* Administered orally<br>|

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 | Data presented are the number of participants who experienced 1 or more SAEs considered by the investigator to be related to study drug administration is reported. SAEs were classified using the Medical Dictionary for Regulatory Activities (MedDRA) 19.1. A summary of non-serious adverse events and all serious adverse events, regardless of causality is located in the Reported Adverse Events section. | Baseline to Study Completion (up to Day 43) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of LY3323795 in plasma. | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72,96,120,144 hours, post dose | 
| Part B Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Cerebrospinal Fluid (CSF) | Part B Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of LY3323795 in cerebrospinal fluid (CSF). | -4, -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36 hours, post dose | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | Pharmacokinetics (PK): Area under the concentration time curve from time zero to tlast (AUC[0-tlast]) of LY3323795 in plasma. | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72,96,120,144 hours, post dose | 
| Part B Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Cerebrospinal Fluid (CSF) | Part B Pharmacokinetics (PK): Area under the concentration time curve from time zero to tlast (AUC[0-tlast]) of LY3323795 in cerebrospinal fluid (CSF). | -4, -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36 hours, post dose | 
| Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Amyloid beta is a peptide fragment of the amyloid precursor protein, plasma concentrations of Aβ1-40 and Aβ1-42 were determined using validated immunoassay methods. | Baseline through 144 hours | 
| Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Amyloid beta is a peptide fragment of the amyloid precursor protein, CSF concentrations of Aβ1-40, Aβ1-42 were determined using validated immunoassay methods. | Baseline through 36 hours |