A Study of LY4515100 in Healthy Participants

Official title

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

Overview

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.

Interventions

• Drug LY4515100 via SAD
  given orally
• Drug LY4515100 via MAD
  given orally
• Drug LY4515100
  given orally
• Drug Itraconazole
  given orally
• Drug Caffeine
  given orally
• Drug Digoxin
  given orally
• Drug Iohexol
  given IV
• Drug Metformin
  given orally
• Drug Rosuvastatin
  given orally
• Drug Placebo
  given orally

Primary outcome measures

• Number of participants with one or more serious adverse event(s) (SAEs) of LY4515100 in Parts A and B [Time frame: Day 1 up to Day 30]

Secondary outcome measures (7)

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

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Basic science

Study locations

United States · 1 center

• Fortrea Clinical Research Unit — Dallas

Identifiers

NCT: NCT07339722 · 27789 · J6V-MC-OIAB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗