LY3875383 for High Triglycerides

Recruiting at 5 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must be taking: Lipid-lowering drugs, Statins

Disqualifiers: Viral infections, Heavy drinkers, Smokers, others

Compensation: Varies

Number of Visits: 1

Duration: 1 week

41 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

If you are participating in Part C or D of the trial, you must continue taking your current lipid-lowering drugs or statins at the same dose throughout the study. The protocol does not specify medication requirements for other parts of the trial.

What data supports the effectiveness of the drug LY3875383 for high triglycerides?

Research shows that treatments like icosapent ethyl, which is an omega-3 fatty acid, have significantly reduced cardiovascular events in patients with high triglycerides, suggesting that similar treatments could be effective. Additionally, studies have shown that reducing triglycerides can directly benefit heart health, indicating that drugs targeting triglycerides may be beneficial. ^{1 2 3 4 5}

What makes the drug LY3875383 unique for treating high triglycerides?

LY3875383 is a novel treatment for high triglycerides, potentially offering a new mechanism of action compared to existing options like fibrates and omega-3 fatty acids, which may not fully address very high triglyceride levels or residual cardiovascular risk. ^{1 3 6 7 8}

Research Team

Call 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)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

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.

Inclusion Criteria

You have a history of very high triglyceride levels, and you need to be on a specific diet and medication for at least 8 weeks before joining the study.

Males who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP)

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

Exclusion Criteria

All participants must not have one of the following viral infections: hepatitis B virus, hepatitis C virus or human immunodeficiency virus (HIV)

All participants must not be currently participating in or completed a clinical trial within the last 30 days

All participants must not have donated blood of more than 500 mL within the previous 3 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of LY3875383 or placebo administered subcutaneously

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 52 weeks

Treatment Details

Interventions

• LY3875383
• Placebo

Trial Overview 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.

Participant Groups

Group I: LY3875383 (Part D) Experimental Treatment 1 Intervention

Single doses of LY3875383 administered SC.

Group II: LY3875383 (Part C) Experimental Treatment 1 Intervention

Single doses of LY3875383 administered SC.

Group III: LY3875383 (Part B) Experimental Treatment 1 Intervention

Single doses of LY3875383 administered SC.

Group IV: LY3875383 (Part A) Experimental Treatment 1 Intervention

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

Group V: Placebo (Part B) Placebo Group 1 Intervention

Placebo administered SC.

Group VI: Placebo (Part A) Placebo Group 1 Intervention

Placebo administered SC.

Group VII: Placebo (Part C) Placebo Group 1 Intervention

Placebo administered SC.

Group VIII: Placebo (Part D) Placebo Group 1 Intervention

Placebo administered SC.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Hypertriglyceridemia is a significant risk factor for cardiovascular disease and acute pancreatitis, highlighting the need for effective treatments beyond existing options like fibrates and ω-3 fatty acids.

Novel therapies, including apolipoprotein C-III inhibitors and fibroblast growth factor 21 analogues, are currently in early clinical development to better manage very high triglyceride levels and reduce cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Investigational and Experimental Therapeutics for the Treatment of Hypertriglyceridemia. Parthymos, I., Kostapanos, MS., Liamis, G., et al.[2022]

SC401, a new ω-3 fatty acid formulation, demonstrated significantly higher bioavailability of EPA and DHA compared to Lovaza, achieving this with a lower dose of 1530 mg versus Lovaza's 3600 mg.

The study found that SC401 had a faster absorption rate, with a shorter time to peak concentration (Tmax) compared to Lovaza, indicating it may be more effective in delivering these essential fatty acids under low-fat feeding conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel ω-3 Acid Ethyl Ester Formulation Incorporating Advanced Lipid TechnologiesTM (ALT®) Improves Docosahexaenoic Acid and Eicosapentaenoic Acid Bioavailability Compared with Lovaza®. Lopez-Toledano, MA., Thorsteinsson, T., Daak, A., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fibrates, Hypertriglyceridemia, and CVD Risk: Where Do We Stand After the PROMINENT Trial for Triglyceride Lowering? [2023]

2. England pubmed.ncbi.nlm.nih.gov

Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslipidaemia therapeutics. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Early Investigational and Experimental Therapeutics for the Treatment of Hypertriglyceridemia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Triglycerides and cardiovascular disease. A focus on clinical trials. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Recent advances in pharmacotherapy for hypertriglyceridemia. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Treatment of Hypertriglyceridemia: A Review of Therapies in the Pipeline. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A Novel ω-3 Acid Ethyl Ester Formulation Incorporating Advanced Lipid TechnologiesTM (ALT®) Improves Docosahexaenoic Acid and Eicosapentaenoic Acid Bioavailability Compared with Lovaza®. [2019]