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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LY3372689; Diagnostic test: [18F]LSN3316612

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Institute for Neurodegenerative Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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• Have previously participated or withdrawn from this study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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Actual): October 14, 2020
• Study Completion (Actual): October 14, 2020

Study Registration Dates

• First Submitted: April 21, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 17243; I9X-MC-MTAD (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No