A Study of LY3875383 in Healthy Participants and Participants With Hypertriglyceridemia

A Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3875383 in Healthy Participants and Participants With Hypertriglyceridemia

The main purpose of this study is to determine the tolerability and side effects related to LY3875383 given as a single injection under the skin to healthy participants and participants with elevated triglyceride (TG) levels.The study will also assess how fast LY3875383 gets into the blood stream and how long the body takes to get rid of it. Each enrolled participant will receive a single dose of either LY3875383 or placebo.The study will be conducted in four parts (A, B, C and D) and may last up to approximately 28 to 56 weeks including screening.

Inclusion Criteria:

All participants:

• Have a body mass index (BMI) between 18.5 and 40 kilograms per square meter (kg/m²), inclusive.
• Males who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP).

Healthy participants (Part A):

• Participants must be overtly healthy, as determined by medical evaluation.

For Part B:

• Participants must be first-generation Japanese, defined as the participant's biological parents, and all of the participant's biological grandparents must be of exclusive Japanese descent and born in Japan.

Hypertriglyceridemia participants (Parts C and D):

For Part C:

• Have history of very high triglyceride (lipid) level 500 mg/dL ≤ TG <2000 mg/dL, which needs to be further confirmed at screening.
• Participants must be on a lipid-modifying diet and can be on stable lipid-lowering drugs (LLDs) for at least 8 weeks before screening and plan to continue the same throughout the study duration.

For Part D:

• Have history of high triglyceride (lipid) level between 150 mg/dL and 500 mg/dL inclusive at pre-screening or based on medical history and confirmed at screening and Low-density lipoprotein cholesterol (LDL-C) level of ≥40 mg/dL.
• Participants must be on a stable moderate or high-intensity dose of a statin for at least 8 weeks before screening and plan to continue the same medication and dose throughout the study duration.

Exclusion Criteria:

All participants:

• Participants must not be currently participating in or completed a clinical trial within the last 30 days
• Have donated blood of more than 500 mL within the previous 3 months
• Have one of the following viral infections: hepatitis B virus, hepatitis C virus or human immunodeficiency virus (HIV).
• Participants must not be heavy alcohol drinkers or cigarette smokers.

For Part C: Have active pancreatitis within the last 6 months