A Study of the Effects of Multiple Doses of LY3372689 on the Brain in Healthy Participants

Study Overview
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Brief Summary
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This study uses imaging to evaluate how LY3372689 binds to a protein in the brain. This study will be conducted in healthy participants and will last up to about 10 weeks. Screening must be completed within four weeks prior to enrollment.

Official Title
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Assessment of Brain O-GlcNAcase (OGA) Enzyme Occupancy After Multiple Oral Doses of LY3372689 as Measured by Positron Emission Tomography (PET) With the Radioligand [18F]LY3316612 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY3372689
* Diagnostic Test: [18F]LSN3316612


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overtly healthy males or females who do not have child-bearing potential Have a body mass index (BMI) of greater than (>)18 to less than or equal to (≤32) kilograms per square meter (kg/m²), inclusive, at screening Have normal blood pressure, pulse rate, electrocardiogram (ECG, heart tracing), blood and urine laboratory test results that are acceptable for the study Have venous access sufficient to allow for blood sampling Exclusion Criteria: Have a history of head injury or contraindications to undergoing magnetic resonance imaging (MRI) examination Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study Have previously participated or withdrawn from this study Have had prior participation in other research protocols or clinical care in the preceding year in addition to the radiation exposure expected from participation in this clinical study, such that radiation exposure exceeds the effective dose of 50 milliSievert (mSv), which would be above the acceptable annual limit established by the US Federal Guidelines Are current smokers or have used tobacco or nicotine-containing products as determined by the cotinine test Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate or could interfere with understanding the results of the study Participate in regular vigorous exercise

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3372689 + [18F]LSN3316612<br>LY3372689 administered orally followed by [18F]LSN3316612 PET tracer administered intravenously (IV) approximately 24 hours later. | Drug: LY3372689<br>* Administered orally.<br>Diagnostic Test: [18F]LSN3316612<br>* Administered intravenously (IV).<br>* Other names: [18F]MNI-1068;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent O-GlcNAcase (OGA) Enzyme Occupancy (EO) | Percent OGA EO | Approximately 2 to 96 hours following the first dose | 
| Percent OGA EO | Percent OGA EO | Approximately 2 to 96 hours following the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve During the Dosing Interval (AUC[0-tau]) of LY3372689 | PK: AUC(0-tau) of LY3372689 | Baseline through 24 hours | 
| PK: Maximum Concentration (Cmax) of LY3372689 | PK: Cmax of LY3372689 | Baseline through 24 hours |