NST-1024 for High Triglycerides

Recruiting in Palo Alto (17 mi)

+30 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: NorthSea Therapeutics B.V.

Must be taking: Statins, Omega-3

Must not be taking: QT prolonging drugs

Disqualifiers: Type 1 diabetes, Stroke, Pancreatitis, others

Stay on Your Current Meds

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase IIa,multicentre proof of concept study consisting of 2 study periods to study Treatment with NST-1024 as an adjunct to diet to reduce triglyceride (TG) levels in subjects with TG levels of ≥500 mg/dL and ≤2000 mg/dL; determined by percentage change in TG from baseline after 28 days of treatment. The two periods consist of: 1. A 3-week screening period that includes a TG qualifying period, and 2. A 28-days, double-blind, randomized, parallel group, placebo-controlled treatment period. Subjects will return to the study site for a follow-up visit 2 weeks after the last dose. Approximately 50 subjects will be randomized at approximately 15-35 centers in USA.

Will I have to stop taking my current medications?

The trial requires that if you are on medications like statins, non-statin lipid-altering therapies, or weight loss drugs, your dosage must be stable for a certain period before and during the study. It doesn't specify stopping other medications, but you should discuss your specific situation with the study team.

What evidence supports the effectiveness of the drug NST-1024 for high triglycerides?

The ACCORD LIPID study shows that adding fenofibrate to statin therapy in patients with high triglycerides and low HDL cholesterol reduced the risk of cardiovascular events by 31%. Additionally, gemfibrozil, a similar drug, has been shown to effectively lower triglycerides and increase HDL cholesterol levels. ^{1 2 3 4 5}

How does the drug NST-1024 for high triglycerides differ from other treatments?

The research does not provide specific information about NST-1024, but it mentions other treatments like micronized fenofibrate, gemfibrozil, and omega-3 fatty acids, which are used to lower triglyceride levels. These treatments work by different mechanisms, such as modifying lipid metabolism or reducing triglyceride production, and are administered in various forms like capsules or tablets. ^{5 6 7 8 9}

Research Team

Eligibility Criteria

This trial is for adults aged 18-79 with very high triglyceride levels (≥500 mg/dL and ≤2000 mg/dL). Participants must understand the study, follow its schedule, and give written consent. Women can join if they're not pregnant or breastfeeding, have had a hysterectomy or tubal ligation, are post-menopausal, or use effective contraception. Men's partners must also use effective birth control.

Inclusion Criteria

You understand the study procedures, agree to follow the study schedules, and are willing to give written consent before the screening assessments.

I have had a complete hysterectomy, tubal ligation, or I am post-menopausal.

I can take medication by mouth.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Includes a TG qualifying period

Treatment

Participants receive NST-1024 400 mg BID or placebo for 28 days in a double-blind, randomized, parallel group, placebo-controlled setting

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• NST-1024 (Other)
• Placebo (Other)

Trial Overview The trial tests NST-1024 against a placebo in reducing triglycerides as an addition to diet changes over 28 days. It's a Phase IIa study with about 50 participants across multiple U.S. centers who will be randomly assigned to either the drug or placebo group in a double-blind setup (neither doctors nor patients know who gets what).

Participant Groups

Group I: NST-1024 Active Control 1 Intervention

NST-1024 400 mg BID

Group II: Matched Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

NorthSea Therapeutics B.V.

Lead Sponsor

Trials

7

Recruited

590+

Findings from Research

Type 2 diabetic patients on statins who had high triglycerides and low HDL cholesterol saw a 31% reduction in cardiovascular events when fenofibrate was added to their treatment.

This means that for every 20 patients treated with fenofibrate over five years, one cardiovascular event could be prevented, highlighting its efficacy in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACCORD LIPID study results strengthen guideline approach of adding fenofibrate to therapy of dyslipidaemic type 2 diabetic patients. Aalbers, J.[2013]

Diet and drug therapy are essential for managing LDL cholesterol levels, with dietary changes focusing on reducing saturated fats and cholesterol, but may not be sufficient alone for high-risk individuals.

Statins are the preferred medication for lowering LDL cholesterol and improving HDL cholesterol in patients with coronary artery disease, while other drugs like bile acid resins and niacin can be used to enhance treatment effects or target specific lipid abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid management: current diet and drug treatment options. Stone, NJ.[2019]

Lower doses of statins and bile acid sequestrants can effectively reduce LDL cholesterol levels, indicating that higher doses may not be necessary for optimal results.

Combining statins with bile acid sequestrants or niacin can provide an additive effect in lowering LDL cholesterol, suggesting a treatment strategy that maximizes efficacy while potentially reducing side effects and costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment. Schectman, G., Hiatt, J.[2019]

A 6-week treatment with lipid-lowering drugs results in consistent post-treatment cholesterol and triglyceride levels, suggesting that measuring absolute values after treatment is more reliable than looking at percentage reductions.

Combining clofibrate with Bufor leads to lower cholesterol levels compared to using either drug alone, while the effects of cholestyramine drugs like Cuemid and Questran cannot be accurately predicted based on previous clofibrate treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential drug therapy of the hyperlipoproteinaemias. The efficacy of lipid lowering drugs alone and in combination. Hansen, PF.[2013]

Gemfibrozil, at a daily dose of 1200 mg, effectively reduces total serum cholesterol, triglycerides, and apo B levels while increasing HDL cholesterol in patients with hyperlipidemia, demonstrating its efficacy as a lipid-lowering agent.

Long-term studies indicate that gemfibrozil has a more significant impact on lowering triglycerides than cholesterol, has few side effects, and maintains its effectiveness over time, making it a promising option for managing lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperlipoproteinemia, atherosclerosis and gemfibrozil. Nash, DT.[2017]

In a 3-month study involving 24 individuals with high triglycerides, gemfibrozil significantly reduced fasting plasma triglyceride levels from 4.01 to 1.34 mmol/L and increased HDL cholesterol from 0.54 to 0.67 mmol/L, indicating its efficacy in improving lipid profiles.

Despite these improvements in triglycerides and cholesterol, gemfibrozil did not affect plasma glucose or insulin responses to meals, suggesting that while it helps with lipid levels, it does not enhance insulin sensitivity or glucose disposal in patients with hypertriglyceridemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations. Jeng, CY., Sheu, WH., Fuh, MM., et al.[2013]

New triglyceride-lowering therapies, including selective PPARα modulators and omega-3 fatty acid formulations, show promise for patients with severe hypertriglyceridemia (HTG) and those at high cardiovascular risk, particularly those with diabetes.

The phase 3 trial REDUCE-IT demonstrated the efficacy of high-dose icosapent ethyl, suggesting that these therapies can be beneficial for patients who are already on statin therapy but still have elevated triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational drugs in development for hypertriglyceridemia: a coming-of-age story. Rhainds, D., Brodeur, MR., Tardif, JC.[2020]

Clinical trials indicate that taking four 1-g capsules of prescription omega-3 ethyl ester fatty acids daily can significantly lower triglyceride levels in patients with very high triglycerides.

The treatment is well tolerated, suggesting it is a safe option for managing high triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating hypertriglyceridemia with prescription omega-3 fatty acid ethyl esters. Mickleborough, TD.[2010]

References

1. South Africa pubmed.ncbi.nlm.nih.gov

ACCORD LIPID study results strengthen guideline approach of adding fenofibrate to therapy of dyslipidaemic type 2 diabetic patients. [2013]

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

Lipid management: current diet and drug treatment options. [2019]

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

Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment. [2019]

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

Differential drug therapy of the hyperlipoproteinaemias. The efficacy of lipid lowering drugs alone and in combination. [2013]

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

Hyperlipoproteinemia, atherosclerosis and gemfibrozil. [2017]

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

Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Investigational drugs in development for hypertriglyceridemia: a coming-of-age story. [2020]

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

Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Treating hypertriglyceridemia with prescription omega-3 fatty acid ethyl esters. [2010]