A Study of LY3154207 in Healthy Participants

Study Overview
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Brief Summary
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This study involves single doses of LY3154207 and will evaluate the effects of LY3154207 on the body. There will be 3 parts to this study. Part A will test single increasing doses of LY3154207 and will last approximately 7 weeks for each participant. Each participant will receive two doses of LY3154207, if part A is completed. Part B will test a single dose of LY3154207 and will last approximately 5 weeks for each participant. Part B includes collecting fluid from the spinal column to measure levels of LY3154207. Part C will include a single dose of LY3154207 given alone and then a second dose given along with itraconazole to look for change in LY3154207 levels. Part C will last about 3 weeks for each participant. Participants may only enroll in 1 of the 3 parts of the study.

Official Title
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Single-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Cytochrome P450 Interaction Study of LY3154207 in Healthy Subjects

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: LY3154207
* Drug: Placebo
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overtly healthy males or females, as determined by medical history and physical examination Female participants not of child-bearing potential Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures Have given written informed consent Have a body mass index (BMI) of 18 to 35 kilograms per square meter (kg/m^2) Exclusion Criteria: Part B only: Have medical or surgical conditions in which lumbar puncture is contraindicated Part C only: Have known allergy or contraindications to itraconazole

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3154207 (Part A)<br>LY3154207 administered in ascending doses once orally in two of three study periods | Drug: LY3154207<br>* Administered orally<br>|
| Placebo Comparator: Placebo (Part A)<br>Placebo matching LY3154207 administered once orally in one of three study periods. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: LY3154207 (Part B)<br>LY3154207 administered once orally. | Drug: LY3154207<br>* Administered orally<br>|
| Placebo Comparator: Placebo (Part B)<br>Placebo matching LY3154207 administered once orally. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: LY3154207 (Part C)<br>LY3154207 administered once orally on Day 1 | Drug: LY3154207<br>* Administered orally<br>|
| Experimental: LY3154207 + Itraconazole (Part C)<br>Itraconazole administered orally (twice daily on Day 3 and then once daily to Day 12). LY3154207 co-administered once orally, on Day 9. Timing and duration of itraconazole dosing may be adjusted based on data from Part A. | Drug: LY3154207<br>* Administered orally<br>Drug: Itraconazole<br>* Administered orally (twice daily on Day 3 and then once daily to Day 12) as a 10 mg/mL solution<br>|

What is the study measuring?
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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 |  | Up to 48 hours after administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) Plasma Part A : Maximum Drug Concentration (Cmax) of LY3154207 |  | Predose through 48 hours after administration of study drug | 
| Pharmacokinetics (PK) Plasma Part A: Area Under the Concentration Curve (AUC) of LY3154207 |  | Predose through 48 hours after administration of study drug | 
| Pharmacokinetics (PK) Cerebrospinal Fluid (CSF) Part B: Area Under the Concentration Time Curve (AUC) of LY3154207 |  | Predose through 48 hours after administration of study drug | 
| Pharmacokinetics (PK) Cerebrospinal Fluid (CSF) Part B: Maximum Drug Concentration (Cmax) of LY3154207 |  | Predose through 48 hours after administration of study drug | 
| Pharmacokinetics (PK) Plasma Part C: Area Under the Concentration Time Curve (AUC) of LY3154207 when Co-administered with Itraconazole |  | Predose through 96 hours after administration of study drug | 
| Pharmacokinetics (PK) Plasma Part C: Maximum Drug Concentration (Cmax) of LY3154207 when Co-administered with Itraconazole |  | Predose through 96 hours after administration of study drug |