What side effects are associated with this type of intervention?

Common treatments for cardiovascular conditions, particularly lipid-lowering agents like statins, PCSK9 inhibitors (e.g., alirocumab, evolocumab), and other novel agents (e.g., bempedoic acid, lomitapide), have various side effects. Statins are generally well-tolerated but can cause muscle pain, liver enzyme abnormalities, and, rarely, rhabdomyolysis. PCSK9 inhibitors are associated with mild injection site reactions, hypersensitivity reactions, and a small increase in neurocognitive symptoms. Bempedoic acid may cause muscle spasms, hyperuricemia, and tendon rupture. Lomitapide can lead to gastrointestinal symptoms, elevated liver enzymes, and hepatic fat accumulation. These side effects should be discussed with a healthcare provider to determine the most appropriate treatment plan.

What prior FDA approvals exist?

Several lipid-lowering agents have received FDA approval for the treatment of cardiovascular conditions. Statins, such as atorvastatin and simvastatin, inhibit HMG-CoA reductase to lower LDL cholesterol. PCSK9 inhibitors, including alirocumab and evolocumab, have been approved for their ability to significantly reduce LDL cholesterol by inhibiting the PCSK9 enzyme, which enhances the liver's ability to remove LDL from the blood. Ezetimibe, another approved drug, works by inhibiting the absorption of cholesterol in the intestines. These treatments have been shown to reduce cardiovascular events and are often used in combination with other lipid-lowering therapies.

What other types of research exist?

Promising novel alternatives to AZD1705 for cardiovascular patients include: 1) Ezetimibe, a cholesterol absorption inhibitor, which can be used alone or in combination with statins. 2) PCSK9 inhibitors like evolocumab and alirocumab, which have shown significant LDL cholesterol reduction and are well-tolerated. 3) CETP inhibitors such as TA-8995, which have demonstrated efficacy in raising HDL and lowering LDL cholesterol without serious side effects.

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Anti-metabolites

AZD1705 for Dyslipidemia

Phase 1

Recruiting

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

All females must have a negative pregnancy test

Male and female of non-childbearing potential participants with suitable veins for cannulation or repeated venipuncture

Must not have

History or presence of gastrointestinal, hepatic, or renal disease or any condition known to interfere with drug metabolism

Timeline

Screening 3 weeks

Treatment Varies

Follow Up part a: from screening (day -60 to day -2) until day 113. part b: from screening until day 141

Summary

This trial tests a new drug called AZD1705 in people with abnormal blood lipid levels. It aims to see if the drug is safe and how it behaves in the body. The study involves different doses and includes monitoring to observe effects.

Who is the study for?

This trial is for Japanese or Chinese adults with dyslipidemia who have stable veins for blood draws, are on a steady statin treatment for at least 3 months, and have a BMI of 18-35. Women must not be able to bear children and need a negative pregnancy test. Smokers or those with recent serious health issues can't join.

What is being tested?

The study tests AZD1705's safety and how the body processes it in people with high lipid levels compared to a placebo (a substance with no active drug). Participants will randomly receive either AZD1705 or the placebo.

What are the potential side effects?

Potential side effects may include reactions related to the digestive system, liver, kidneys, blood values like abnormal hemoglobin levels, vital signs changes, ECG alterations or other organ-specific inflammation due to drug metabolism interference.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am not pregnant.

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I am not able to have children and have veins suitable for frequent needle insertions.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a condition that affects how drugs are broken down in my body.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ part a: from screening (day -60 to day -2) until day 113. part b: from screening until day 141

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~part a: from screening (day -60 to day -2) until day 113. part b: from screening until day 141

This trial's timeline: 3 weeks for screening, Varies for treatment, and part a: from screening (day -60 to day -2) until day 113. part b: from screening until day 141 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Number of participants with adverse events (AEs) and serious adverse events (SAEs)

Secondary study objectives

Area under plasma concentration-time curve from zero extrapolated to infinity (AUCinf)

Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)

Change from baseline in Apolipoprotein B (ApoB)

+7 more

Trial Design

12Treatment groups

Active Control

Placebo Group

Group I: Part B2 (AZD1705)Active Control1 Intervention

Japanese participants not receiving statin therapy will receive AZD1705 subcutaneously on Day 1 and Day 29.

Group II: Part B3 (AZD1705)Active Control1 Intervention

Participants who may or may not be receiving moderate- or high-intensity statin therapy and with the additional diagnosis of type 2 diabetes will receive AZD1705 subcutaneously on Day 1 and Day 29.

Group III: Part A1 (AZD1705)Active Control1 Intervention

Non-Asian participants will receive AZD1705 subcutaneously on Day 1.

Group IV: Part A2 (AZD1705)Active Control1 Intervention

Japanese participants will receive AZD1705 subcutaneously on Day 1.

Group V: Part A3 (AZD1705)Active Control1 Intervention

Chinese participants will receive AZD1705 subcutaneously on Day 1.

Group VI: Part B1 (AZD1705)Active Control1 Intervention

Non-Asian participants who may or may not be receiving moderate- or high-intensity statin therapy will receive AZD1705 subcutaneously on Day 1 and Day 29.

Group VII: Part A3 (Placebo)Placebo Group1 Intervention

Chinese participants will receive placebo on Day 1.

Group VIII: Part A2 (Placebo)Placebo Group1 Intervention

Japanese participants will receive placebo on Day 1.

Group IX: Part A1 (Placebo)Placebo Group1 Intervention

Non-Asian participants will receive placebo on Day 1.

Group X: Part B2 (Placebo)Placebo Group1 Intervention

Japanese participants not receiving statin therapy will receive placebo on Day 1 and Day 29.

Group XI: Part B3 (Placebo)Placebo Group1 Intervention

Participants who may or may not be receiving moderate- or high-intensity statin therapy and with the additional diagnosis of type 2 diabetes will receive placebo on Day 1 and Day 29.

Group XII: Part B1 (Placebo)Placebo Group1 Intervention

Non-Asian participants who may or may not be receiving moderate- or high-intensity statin therapy will receive placebo on Day 1 and Day 29.

0 / 3Eligibility criteria met

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

Lipid-lowering agents are crucial in managing cardiovascular disease by targeting specific enzymes or receptors involved in lipid metabolism. Statins inhibit HMG-CoA reductase, reducing cholesterol synthesis in the liver. PCSK9 inhibitors, such as evolocumab and alirocumab, prevent PCSK9 from degrading LDL receptors, enhancing the clearance of LDL cholesterol from the bloodstream. Emerging therapies like bempedoic acid and inclisiran further inhibit cholesterol synthesis or PCSK9 production, respectively. These treatments are vital for cardiovascular patients as they significantly lower LDL cholesterol levels, reducing the risk of atherosclerotic events such as heart attacks and strokes.

Do we need new lipid-lowering agents in the era of PCSK9 inhibitors? Recent advances.Mode of action of lipid-lowering drugs.