A Study of LY3526318 in Healthy Male Japanese Participants

A Phase I, Single-Centre Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of LY3526318, and to Investigate the Effect of LY3526318 on Metformin and Simvastatin Pharmacokinetics in Healthy Male Japanese Participants

This is a study of LY3526318 in healthy male Japanese. The main purposes of this study are to:

• Assess how safe and well tolerated LY3526318 is when given by mouth.
• Measure how LY3526318 affects the kidney and the liver. The study will be conducted in three parts (Part A, Part B, Part C). Participants may only enroll in one part. After screening, the study will last from one to two weeks, depending on part.

Study Overview

• Status: Withdrawn
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Metformin; Drug: LY3526318; Drug: Simvastatin; Drug: Iohexol

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 813-0017
    • Souseikai Fukuoka Mirai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male Japanese participants who are overtly healthy as determined by medical evaluation including medical history and physical examination.
• Body weight of at least 50 kilogram (kg) and body mass index within the range 18 to 30 kilogram per square meter (kg/m2).
• Male participants must adhere to the contraceptive requirements.
• Have clinical laboratory test results within normal reference range for the population or clinical research unit (CRU), or results with acceptable deviations that are judged not clinically significant by the investigator.

Exclusion Criteria:

• Have a history or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, or convulsions that, in the judgment of the investigator, indicate a medical problem that would preclude study participation.
• Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study. In addition, participants with the following finding will be excluded:
• Have a history of clinically significant multiple or severe drug allergies or severe posttreatment hypersensitivity reactions.
• Show evidence of human immunodeficiency virus and/or positive human immunodeficiency virus antigens and/or antibodies, hepatitis C and/or positive hepatitis C antibody, or hepatitis B and/or positive hepatitis B surface antigen.
• Show evidence of syphilis or have a positive syphilis test.
• Have an abnormal blood pressure (supine) as determined by the investigator.
• Are unwilling to stop herbal supplements, over-the-counter, or prescription medicines, including drugs that are known inducers or inhibitors of cytochrome P450 3A4 (CYP3A4), within 14 days prior to study intervention administration and for the duration of the study. An exception is for acetaminophen at doses of less than or equal to (≤3) grams/day.
• Participated (defined as last dose of study drug) within 30 days prior to dosing in a clinical trial involving an investigational product or nonapproved use of a drug with a short half-life, or within 5 half-lives of an investigational product with a half-life longer than 6 days.
• Participants with a history of drug abuse which, in the opinion of the investigator, is clinically significant or who test positive for drugs of abuse at screening or admission.
• Are unwilling to comply with the required dietary restrictions.

Additional Exclusion Criteria of Part C:

• Have known allergies to iohexol, iodine, simvastatin, metformin, and related compounds or any components of the formulation.
• Show evidence of CYP3A5 *1 allele (CYP3A5*1/*1 or CYP3A5*1/*3).
• Confirmed creatinine clearance <90 milliliter per minute (mL/min) at the screening period assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Single Dose LY3526318; LY3526318 administered orally in three study periods.	Drug: LY3526318; Administered orally.
Placebo Comparator: Part A: Single Dose Placebo; Placebo administered orally in three study periods.	Drug: Placebo; Administered orally.
Experimental: Part B: Multiple Dose LY3526318; LY3526318 administered orally.	Drug: LY3526318; Administered orally.
Placebo Comparator: Part B: Multiple Dose Placebo; Placebo administered orally.	Drug: Placebo; Administered orally.
Experimental: Part C: Iohexol + Simvastatin + Metformin + LY3526318; Iohexol administered intravenously (IV) and simvastatin, metformin, and LY3526318 administered orally.	Drug: Metformin; Administered orally.; Drug: LY3526318; Administered orally.; Drug: Simvastatin; Administered orally.; Drug: Iohexol; Administered intravenously (IV).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and B: 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 SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.	Baseline through Day 12
Part C: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Metformin	PK: Cmax of metformin.	Predose on Day -2 through Day 8
Part C: PK: Area Under the Concentration Versus Time Curve (AUC) of Metformin	PK: AUC of metformin.	Predose on Day -2 through Day 8
Part C: PK: Total Body Clearance (CL) of Iohexol	PK: CL of Iohexol.	Predose on Day -5 through Day 4
Part C: PK: Cmax of Simvastatin	PK: Cmax of simvastatin.	Predose on Day -4 through Day 6
Part C: PK: AUC of Simvastatin	PK: AUC of Simvastatin.	Predose on Day -4 through Day 6
Part C: PK: Cmax of Simvastatin Acid	PK: Cmax of Simvastatin Acid.	Predose on Day -4 through Day 6
Part C: PK: AUC of Simvastatin Acid	PK: AUC of Simvastatin Acid.	Predose on Day -4 through Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A, B, and C: PK: Cmax of LY3526318	PK: Cmax of LY3526318.	Predose on Day 1 up to Day 14
Part A, B, and C: PK: AUC of LY3526318	PK: AUC of LY3526318.	Predose on Day 1 up to Day 14

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2022
• Primary Completion (Actual): December 8, 2022
• Study Completion (Actual): December 8, 2022

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 12, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Metformin; Simvastatin
• Other Study ID Numbers: 18353; J2D-JE-CVAD (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: No
• Studies a U.S. FDA-regulated device product: No