A Study of LY4515100 in Healthy Participants

A Phase 1, Randomized, Investigator- and Participant-Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Characterize the Safety, Tolerability, and Pharmacokinetics of LY4515100 in Healthy Participants and an Open-Label Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics, Safety, and Tolerability of LY4515100 and of LY4515100 on the Pharmacokinetics of CYP and Transporter Substrates in Healthy Participants

The main purpose of this study is to assess the safety and tolerability of LY4515100 when given orally to healthy participants. LY4515100 will be given by itself or with other medicines. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. The study will have 3 parts and will last about 50 days. For each participant in Part A, the study will include a stay in the Clinical Research Unit (CRU) lasting about 6 days. For each participant in Part B, the study will include a stay in the CRU lasting about 15 days. For each participant in Part C, the study will include up to 2 stays in the CRU each lasting between 7-28 days.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: LY4515100 via SAD; Drug: LY4515100 via MAD; Drug: LY4515100; Drug: Itraconazole; Drug: Metformin; Drug: Caffeine; Drug: Digoxin; Drug: Iohexol; Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Estimated): 123
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: LillyTrials@Lilly.com
• Study Contact Backup: Name: Physicians interested in becoming principal investigators please contact; Email: clinical_inquiry_hub@lilly.com

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Recruiting
      • Fortrea Clinical Research Unit
      • Principal Investigator: Gene Voskuhl
      • Contact: Phone Number: 866-429-3700

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs, and cardiac monitoring.
• Have a body mass index within the range of 18.5 to 32.0 kilograms per square meter (kg/m²) (inclusive).
• Individuals not of childbearing potential (INOCBP) may participate in this trial.

Exclusion Criteria:

• Have donated 500 milliliters (mL) of blood within 30 days prior to dosing.
• Have participated within the last 30 days in a clinical study involving an investigational medicinal product. If the previous investigational product (IP) has a long half-life, 5 half-lives or 30 days (whichever is longer) should have passed.
• Participants with hemoglobin outside of the local laboratory normal reference range for age and sex, which is judged to be clinically significant by the investigator.
• Participants with an estimated glomerular filtration rate <90 mL/min/1.73 m².
• Have a 12-lead Electrocardiogram (ECG) abnormality that, in the opinion of the investigator,
• increases the risks associated with participating in the study
• may confound ECG data analysis
• Have used or intend to use over-the-counter or prescription medication including dietary or herbal medications within 7 days, or 14 days if the medication is a potential enzyme inducer, or 5 half-lives (whichever is longer), prior to dosing.
• Smoke more than 10 cigarettes per day or the equivalent, including electronic cigarettes, and are unable to abide by investigative site smoking restrictions.
• Have an average weekly alcohol intake that exceeds 14 units per week (males 65 years of age or younger) and 7 units per week (females and males greater than 65 years of age, if applicable)
• Show evidence of
• Human immunodeficiency virus (HIV) infection and/or positive human HIV antigen and/or antibodies
• hepatitis C and/or positive hepatitis C antibody
• hepatitis B and/or positive hepatitis B surface antigen.
• Have liver disease.
• Any clinical condition or procedure (for example, gastrointestinal obstruction, gastric bypass, or cholecystectomy) that may affect the absorption, distribution, or excretion of the study drug and confound pharmacokinetics (PK) assessment.

• Part C Only:

  • Have history of neuropathy of any cause.
  • Have impaired hearing or a history of hearing problems.
  • Have any medical conditions, medical history, or are taking any medications that are contraindicated in the itraconazole prescribing information, such as prior history of hypersensitivity to itraconazole or other azoles.
  • Participants with any known history of thyroid disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY4515100 of Part A (SAD); Single-ascending doses of LY4515100 will be given orally	Drug: LY4515100 via SAD; given orally
Experimental: LY4515100 of Part B (MAD); Multiple-ascending doses of LY4515100 will be given orally	Drug: LY4515100 via MAD; given orally
Placebo Comparator: Placebo Part A; Placebo will be given orally	Drug: Placebo; given orally
Placebo Comparator: Placebo Part B; Placebo will be given orally	Drug: Placebo; given orally
Experimental: LY4515100 and Itraconazole of Part C; LY4515100 and Itraconazole will be given orally	Drug: LY4515100; given orally; Drug: Itraconazole; given orally
Experimental: LY4515100 and Metformin of Part C; LY4515100 and Metformin will be given orally	Drug: LY4515100; given orally; Drug: Metformin; given orally
Experimental: LY4515100 and Transporter Substrates or Renal Marker of Part C; LY4515100 and Transporter Substrates or Renal Marker will be given either orally or intravenously (IV)	Drug: LY4515100; given orally; Drug: Caffeine; given orally; Drug: Digoxin; given orally; Drug: Iohexol; given IV; Drug: Rosuvastatin; given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with one or more serious adverse event(s) (SAEs) of LY4515100 in Parts A and B	SAEs of LY4515100	Day 1 up to Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration versus Time Curve (AUC) of LY4515100	PK: AUC of LY4515100	Day 1 through Day 11
PK: Time of maximum observed drug concentration (tmax) of LY4515100	PK: tmax of LY4515100	Day 1 through Day 11
PK: Maximum Observed Drug Concentration (Cmax) of LY4515100	PK: Cmax of LY4515100	Day 1 through Day 11
PK: Geometric Means of Area Under the Concentration-Time Curve From 0 to Infinity [AUC(0-∞)] of LY4515100 in Combination with Itraconazole versus LY4515100 Alone		Day 1 through Day 50
PK: Geometric Means of Cmax of LY4515100 in Combination with Itraconazole versus LY4515100 Alone		Day 1 through Day 50
PK: Geometric Means of AUC(0-∞) of Substrate in Combination with LY4515100 versus Substrate Alone		Day 1 through Day 36
PK: Geometric Means of Cmax of Substrate in Combination with LY4515100 versus Substrate Alone		Day 1 through Day 36

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: January 6, 2026
• First Posted (Actual): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 29, 2026
• Last Update Submitted That Met QC Criteria: July 28, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Carboxylic Acids; Alkaloids; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Amides; Purinones; Purines; Pyrimidines; Steroids; Fused-Ring Compounds; Benzene Derivatives; Hydrocarbons, Halogenated; Biguanides; Guanidines; Amidines; Acids, Carbocyclic; Sulfonamides; Sulfones; Benzoates; Triazoles; Fluorobenzenes; Hydrocarbons, Fluorinated; Piperazines; Xanthines; Triiodobenzoic Acids; Iodobenzoates; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Rosuvastatin Calcium; Digoxin; Metformin; Caffeine; Itraconazole; Iohexol
• Other Study ID Numbers: 27789; J6V-MC-OIAB (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