What is the mechanism of action of this treatment?

Common treatments for high triglycerides work through various mechanisms to reduce triglyceride levels in the blood. Lifestyle modifications, such as diet and exercise, are foundational and help by reducing overall fat intake and increasing metabolism. Medications like fibrates activate peroxisome proliferator-activated receptors (PPARs) to increase the oxidation of fatty acids and reduce triglyceride synthesis. Omega-3 fatty acids decrease triglyceride production in the liver and increase their clearance from the blood. Niacin reduces the liver's production of triglycerides and very-low-density lipoprotein (VLDL). Statins primarily lower cholesterol but also have a modest effect on triglycerides by inhibiting HMG-CoA reductase, reducing the liver's production of cholesterol and triglycerides. These mechanisms are crucial for patients with high triglycerides as they help prevent complications such as pancreatitis and cardiovascular disease by lowering the risk associated with elevated triglyceride levels.

What side effects are associated with this type of intervention?

Common treatments for high triglycerides include PCSK9 inhibitors, omega-3 fatty acids, and other lipid-lowering agents. PCSK9 inhibitors, such as alirocumab and evolocumab, are generally well-tolerated but can cause side effects like injection site reactions, nasopharyngitis, and flu-like symptoms. Omega-3 fatty acids are usually safe but may lead to gastrointestinal issues such as nausea, diarrhea, and a fishy aftertaste. Other lipid-lowering agents, like fibrates, can cause muscle pain, liver enzyme abnormalities, and gastrointestinal discomfort. It is important to discuss these potential side effects with a healthcare provider to determine the most appropriate treatment.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of high triglycerides, including fibrates (e.g., fenofibrate and gemfibrozil), omega-3 fatty acid formulations (e.g., icosapent ethyl), and niacin. Fibrates work by activating peroxisome proliferator-activated receptors (PPARs) to increase the oxidation of fatty acids and reduce triglyceride levels. Omega-3 fatty acids reduce hepatic production of triglycerides and increase their clearance from the bloodstream. Niacin decreases the liver's production of VLDL and LDL, which in turn lowers triglycerides. These treatments have been shown to be effective in reducing triglyceride levels, though they come with varying safety profiles and potential side effects.

What other types of research exist?

Promising novel alternatives to LY3875383 for high triglycerides include LXR inverse agonists, which inhibit lipogenesis, and PCSK9 inhibitors, which lower LDL cholesterol and may have beneficial effects on triglycerides. Both options have shown potential in clinical studies for treating hyperlipidemia.

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Monoclonal Antibodies

LY3875383 for High Triglycerides

Phase 1

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up predose up to 72 hours post dose

Summary

This trial is testing a new drug called LY3875383, given as a single injection under the skin. It aims to see if the drug is safe and what side effects it might have. The study includes both healthy people and those with high levels of triglycerides, a type of fat in the blood. Researchers will also measure how quickly the drug gets into the bloodstream and how long it stays there.

Who is the study for?

This trial is for healthy individuals and those with high triglycerides. Men must agree to use contraception, women should not be of childbearing potential. Participants need a BMI between 18.5-40 kg/m², and depending on the study part, have specific levels of triglycerides or LDL cholesterol and may need to be on stable lipid-lowering drugs or statins.

What is being tested?

The study tests LY3875383's tolerability as a single under-the-skin injection in comparison to a placebo. It will check how quickly it enters the bloodstream and its elimination rate from the body over four parts (A-D), lasting up to about 28-56 weeks including screening.

What are the potential side effects?

While specific side effects are not listed, common reactions might include irritation at the injection site, general discomfort, allergic reactions or systemic effects due to changes in lipid metabolism caused by LY3875383.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ predose up to 72 hours post dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~predose up to 72 hours post dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and predose up to 72 hours post dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Therapeutic procedure

Secondary study objectives

PK: Maximum Observed Concentration (Cmax) of LY3875383

Triglycerides

Part D only: PD: Percentage Change from Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (HDL-C)

+1 more

Trial Design

8Treatment groups

Experimental Treatment

Placebo Group

Group I: LY3875383 (Part D)Experimental Treatment1 Intervention

Single doses of LY3875383 administered SC.

Group II: LY3875383 (Part C)Experimental Treatment1 Intervention

Single doses of LY3875383 administered SC.

Group III: LY3875383 (Part B)Experimental Treatment1 Intervention

Single doses of LY3875383 administered SC.

Group IV: LY3875383 (Part A)Experimental Treatment1 Intervention

Single-ascending doses of LY3875383 administered subcutaneously (SC).

Group V: Placebo (Part B)Placebo Group1 Intervention

Placebo administered SC.

Group VI: Placebo (Part A)Placebo Group1 Intervention

Placebo administered SC.

Group VII: Placebo (Part C)Placebo Group1 Intervention

Placebo administered SC.

Group VIII: Placebo (Part D)Placebo Group1 Intervention

Placebo administered SC.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

LY3875383

2022

Completed Phase 1

~50

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for high triglycerides work through various mechanisms to reduce triglyceride levels in the blood. Lifestyle modifications, such as diet and exercise, are foundational and help by reducing overall fat intake and increasing metabolism. Medications like fibrates activate peroxisome proliferator-activated receptors (PPARs) to increase the oxidation of fatty acids and reduce triglyceride synthesis. Omega-3 fatty acids decrease triglyceride production in the liver and increase their clearance from the blood. Niacin reduces the liver's production of triglycerides and very-low-density lipoprotein (VLDL). Statins primarily lower cholesterol but also have a modest effect on triglycerides by inhibiting HMG-CoA reductase, reducing the liver's production of cholesterol and triglycerides. These mechanisms are crucial for patients with high triglycerides as they help prevent complications such as pancreatitis and cardiovascular disease by lowering the risk associated with elevated triglyceride levels.