AZD1705 for Dyslipidemia

Recruiting at 5 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Statins, Antacids, Analgesics, others

Disqualifiers: Gastrointestinal, Hepatic, Renal, others

Compensation: Varies

Number of Visits: Unknown

112 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial requires that participants be on stable medication for at least 3 months before joining and not change their medication or dose during the study. So, you can continue your current medications as long as they have been stable for the required time.

What data supports the effectiveness of the drug AZD1705 for dyslipidemia?

Statins, a class of drugs used to treat dyslipidemia, have been shown to effectively lower LDL cholesterol levels and reduce the risk of heart disease. They are well-tolerated and have additional benefits on triglycerides and HDL cholesterol levels, which are important for managing dyslipidemia. ^{1 2 3 4 5}

Eligibility Criteria

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.

Inclusion Criteria

I have high cholesterol or triglycerides.

BMI between 18 and 35 kg/m^2

Participants are to be Japanese, defined as having both parents and 4 grandparents who are Japanese

Exclusion Criteria

Contraindication to MRI as specified

I have no significant health issues that could affect the study.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

8-9 weeks

Treatment Part A

Participants receive a single ascending dose of AZD1705 or placebo with an in-clinic period of 3 days

3 days

Follow-up Part A

Participants are monitored for safety and effectiveness after the single dose treatment

16 weeks

Treatment Part B

Participants receive multiple ascending doses of AZD1705 or placebo, given 28 days apart with an in-clinic period

4 weeks

Follow-up Part B

Participants are monitored for safety and effectiveness after the multiple dose treatment

20 weeks

Treatment Details

Interventions

• AZD1705

Trial Overview 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.

Participant Groups

Group I: Part B2 (AZD1705) Active Control 1 Intervention

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

Group II: Part B3 (AZD1705) Active Control 1 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 Control 1 Intervention

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

Group IV: Part A2 (AZD1705) Active Control 1 Intervention

Japanese participants will receive AZD1705 subcutaneously on Day 1.

Group V: Part A3 (AZD1705) Active Control 1 Intervention

Chinese participants will receive AZD1705 subcutaneously on Day 1.

Group VI: Part B1 (AZD1705) Active Control 1 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 Group 1 Intervention

Chinese participants will receive placebo on Day 1.

Group VIII: Part A2 (Placebo) Placebo Group 1 Intervention

Japanese participants will receive placebo on Day 1.

Group IX: Part A1 (Placebo) Placebo Group 1 Intervention

Non-Asian participants will receive placebo on Day 1.

Group X: Part B2 (Placebo) Placebo Group 1 Intervention

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

Group XI: Part B3 (Placebo) Placebo Group 1 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 Group 1 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.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

Primary dyslipidemias can lead to a higher risk of atherosclerotic vascular diseases, making it crucial to manage cholesterol and triglyceride levels effectively.

When lifestyle changes like diet and exercise are not enough to control lipid levels, pharmacologic treatments are necessary and can significantly lower the risks of serious health issues related to atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Control of lipid disorders in patients with atherosclerotic vascular disease. Marks, AD.[2019]

Patients with type 2 diabetes benefit more from lipid-lowering treatments like ezetimibe and PCSK9 inhibitors due to their higher risk of atherosclerotic cardiovascular disease (ASCVD), as shown in recent clinical trials.

International guidelines now recommend a more aggressive approach to managing dyslipidaemia in diabetes, suggesting that additional therapies should be considered based on individual ASCVD risk and lipid levels, alongside lifestyle changes and statin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Best practice for treating dyslipidaemia in patients with diabetes based on current international guidelines. Lan, NSR., Burns, K., Bell, DA., et al.[2021]

Statins, a class of HMG-CoA reductase inhibitors, are highly effective in lowering LDL cholesterol levels and significantly reduce the risk of coronary heart disease and overall mortality, as demonstrated in large intervention studies.

Statins are generally well tolerated by patients, leading to high compliance rates, and preliminary results suggest they may also effectively reduce triglyceride levels in patients with hypertriglyceridemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical positioning of HMG-CoA reductase inhibitors in lipid management protocols. Cziraky, M.[2018]

Statins are effective for managing dyslipidemia in type 2 diabetes patients, but many do not reach their LDL-C goals, and about 20% experience muscle-related side effects, leading to statin intolerance.

New treatments like ezetimibe and PCSK9 monoclonal antibodies have shown significant cardiovascular benefits and a strong safety profile, offering alternative options for patients struggling with statin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment. Sugiyama, K., Saisho, Y.[2023]

Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the risk of coronary heart disease (CHD), but addressing low high-density lipoprotein cholesterol (HDL-C) and high triglyceride (TG) levels is also important for comprehensive treatment.

Statins are effective first-line treatments for dyslipidemia, primarily lowering LDL-C while also positively affecting TG and HDL-C levels; however, combining statins with other therapies may improve lipid profiles but can lead to side effects and tolerability issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDL-C and triglyceride levels: relationship to coronary heart disease and treatment with statins. Gaw, A.[2019]

References

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

Control of lipid disorders in patients with atherosclerotic vascular disease. [2019]

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

Best practice for treating dyslipidaemia in patients with diabetes based on current international guidelines. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical positioning of HMG-CoA reductase inhibitors in lipid management protocols. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment. [2023]

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

HDL-C and triglyceride levels: relationship to coronary heart disease and treatment with statins. [2019]