A Study of LY3526318 in Healthy Male Japanese Participants

NCT05580250 | Withdrawn Phase 1

• 2 other identifiers: 18353J2D-JE-CVAD
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (2)

• Part A, B, and C: PK: Cmax of LY3526318

  Predose on Day 1 up to Day 14

• Part A, B, and C: PK: AUC of LY3526318

  Predose on Day 1 up to Day 14

Study Arms (5)

Part A: Single Dose LY3526318

EXPERIMENTAL

LY3526318 administered orally in three study periods.

Drug: LY3526318

Part A: Single Dose Placebo

PLACEBO COMPARATOR

Placebo administered orally in three study periods.

Drug: Placebo

Part B: Multiple Dose LY3526318

EXPERIMENTAL

LY3526318 administered orally.

Drug: LY3526318

Part B: Multiple Dose Placebo

PLACEBO COMPARATOR

Placebo administered orally.

Drug: Placebo

Part C: Iohexol + Simvastatin + Metformin + LY3526318

EXPERIMENTAL

Iohexol administered intravenously (IV) and simvastatin, metformin, and LY3526318 administered orally.

Drug: LY3526318; Drug: Iohexol; Drug: Simvastatin; Drug: Metformin

Interventions

LY3526318 DRUG

Administered orally.

Part A: Single Dose LY3526318; Part B: Multiple Dose LY3526318; Part C: Iohexol + Simvastatin + Metformin + LY3526318

Placebo DRUG

Administered orally.

Part A: Single Dose Placebo; Part B: Multiple Dose Placebo

Iohexol DRUG

Administered intravenously (IV).

Part C: Iohexol + Simvastatin + Metformin + LY3526318

Simvastatin DRUG

Administered orally.

Part C: Iohexol + Simvastatin + Metformin + LY3526318

Metformin DRUG

Administered orally.

Part C: Iohexol + Simvastatin + Metformin + LY3526318

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Souseikai Fukuoka Mirai Hospital

Fukuoka, 813-0017, Japan

Location

MeSH Terms

Interventions

Iohexol; Simvastatin; Metformin

Intervention Hierarchy (Ancestors)

Triiodobenzoic Acids; Iodobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Biguanides; Guanidines; Amidines

Study Officials

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Part A and B are double blind and Part C is an open-label study.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 14, 2022
• Study Start: November 22, 2022
• Primary Completion: December 8, 2022
• Study Completion: December 8, 2022
• Last Updated: January 9, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)