AZD0780 for High Cholesterol

Recruiting at 2 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Antacids, Analgesics, Herbal remedies, others

Disqualifiers: Gastrointestinal, Hepatic, Renal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

183 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called AZD0780 to see if it is safe and how it works in the body. The study involves healthy adults, including some with high cholesterol. Researchers will monitor how the drug is processed in the body and its effects on cholesterol levels.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescribed or nonprescribed medications, including antacids, pain relievers, herbal remedies, and vitamins, for at least 2 weeks before starting the trial.

What evidence supports the effectiveness of the drug AZD0780 for high cholesterol?

Research shows that aggressively lowering LDL cholesterol (the 'bad' cholesterol) can significantly reduce the risk of heart disease. Newer statins, like rosuvastatin, have been found to be more effective than older ones in lowering LDL cholesterol, suggesting that AZD0780 might also be effective if it works similarly. ^{1 2 3 4 5}

Is AZD0780 safe for humans?

There is no specific safety data available for AZD0780, but similar drugs called statins are generally well tolerated in humans. However, they can sometimes cause side effects related to muscles, liver, kidneys, and the nervous system. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for healthy adults aged 18-55 with suitable veins for cannulation, a BMI of 18-35 kg/m2, and weighing between 50-120 kg. Japanese or Chinese heritage individuals are eligible based on specific criteria. Women must not be pregnant or able to become pregnant. Participants should have LDL-C levels within certain ranges and cannot have had significant medical procedures, drug abuse history, excessive alcohol consumption, recent vaccinations, or any condition affecting drug absorption.

Inclusion Criteria

Provision of signed and dated, written informed consent prior to any study specific procedures (including the Pre Screening Visit for Part B)

Females must have a negative pregnancy test at the Screening Visit and on admission to the study center, must not be lactating and must be of non childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria: Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range, Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation, Have a BMI between 18 and 35 kg/m2 inclusive and weigh at least 50 kg and no more than 120 kg inclusive at the Screening Visit and on admission to the study center

Criterion: If you are Japanese or Chinese, you have specific requirements for your family background and birthplace. Additionally, your cholesterol and triglyceride levels must meet certain standards for different parts of the study.

Exclusion Criteria

You have a history of drinking too much alcohol.

I received my first COVID-19 vaccine within the last 30 days.

I received my second COVID-19 vaccine shot within the last 10 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

28 days

Treatment Part A

Single dose administration of AZD0780 or placebo, followed by a high-calorie, high-fat breakfast to assess the effect of food on PK

3 days

In-patient stay from Day -1 or Day -2 to Day 3

Follow-up Part A

Follow-up visits to monitor safety and pharmacokinetics after single dose administration

11 days

2 visits (5-7 days and 9-11 days post-dose)

Treatment Part B

Multiple ascending dose administration of AZD0780 or placebo, including specific cohorts for Japanese subjects and combination with rosuvastatin

28 days

In-patient and out-patient visits as per cohort schedule

Follow-up Part B

Follow-up visits to monitor safety and pharmacokinetics after multiple dose administration

2 weeks

2 visits (1 and 2 weeks post last dose)

Treatment Details

Interventions

• AZD0780
• Placebo

Trial Overview The study tests the safety and effects of AZD0780 on cholesterol levels in healthy subjects with/without high LDL-C. It involves single/multiple doses compared against Rosuvastatin (a known cholesterol-lowering medication) and Placebo over two parts involving up to 172 participants.

Participant Groups

Group I: Cohort 5: Part A1 - AZD0780 dose 5/placebo tablet Active Control 2 Interventions

A total of 6 subjects will receive single ascending doses of AZD0780 and 2 will receive placebo.

Group II: Cohort 14: Part B - AZD0780 with placebo tablet/AZD0780 with rosuvastatin dose 12 Active Control 3 Interventions

A total of 20 subjects will receive AZD0780 in combination with rosuvastatin or 5 subjects will receive placebo in combination with rosuvastatin.

Group III: Cohort 13: Part B - placebo tablet/rosuvastatin dose 12 Active Control 2 Interventions

A total of 20 subjects will receive single dose of placebo and rosuvastatin.

Group IV: Cohort 12: Part B - AZD0780 dose 1/rosuvastatin dose 12 Active Control 2 Interventions

A total of 20 subjects will receive single dose of AZD0780 and rosuvastatin.

Group V: Cohort 10: Part B - AZD0780 dose 10/placebo tablet Active Control 2 Interventions

A total of 6 subjects will receive single and multiple ascending doses of AZD0780 and 2 will receive placebo.

Group VI: Cohort 4: Part A1 - AZD0780 dose 4/placebo tablet Active Control 2 Interventions

A total of 6 subjects will receive single ascending doses of AZD0780 and 2 will receive placebo.

Group VII: Cohort 6: Part B - AZD0780 dose 6/placebo tablet Active Control 2 Interventions

A total of 20 subjects will be assigned as 3:1::AZD0780:Placebo to receive multiple ascending doses.

Group VIII: Cohort 7: Part B - AZD0780 dose 7/placebo tablet Active Control 2 Interventions

A total of 20 subjects will be assigned as 3:1::AZD0780:Placebo to receive multiple ascending doses.

Group IX: Cohort 2: Part A1 - AZD0780 dose 2/placebo tablet Active Control 2 Interventions

A total of 6 subjects will receive single ascending doses of AZD0780 and 2 will receive placebo.

Group X: Cohort 3: Part A1 - AZD0780 dose 3/placebo tablet Active Control 2 Interventions

A total of 6 subjects will receive single ascending doses of AZD0780 and 2 will receive placebo.

Group XI: Cohort 9: Part B - AZD0780 dose 9/placebo tablet Active Control 2 Interventions

A total of 6 subjects will receive single and multiple ascending doses of AZD0780 and 2 will receive placebo.

Group XII: Cohort 11: Part A2 - AZD0780 dose 11/placebo tablet Active Control 2 Interventions

A total of 5 subjects will receive single ascending doses of AZD0780 and placebo.

Group XIII: Cohort 8: Part B - AZD0780 dose 8/placebo tablet Active Control 2 Interventions

A total of 20 subjects will be assigned as 3:1::AZD0780:Placebo to receive multiple ascending doses.

Group XIV: Cohort 1: Part A1 - AZD0780 dose 1/placebo tablet Active Control 2 Interventions

A total of 6 subjects will receive single ascending doses of AZD0780 and 2 will receive placebo.

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

Aggressive lowering of LDL cholesterol is beneficial for reducing atherosclerotic disease, but achieving recommended levels with standard doses of lipid-lowering agents has been challenging.

Rosuvastatin has been shown in phase III clinical trials to provide significantly greater reductions in LDL cholesterol compared to other statins, making it a promising option for patients with high cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The lower the better? Reviewing the evidence for more aggressive cholesterol reduction and goal attainment. Stein, E.[2019]

Rosuvastatin, a new statin, has shown significant dose-dependent reductions in LDL cholesterol (LDL-C) ranging from 34% to 65% compared to placebo, indicating its efficacy in lowering cholesterol levels in hypercholesterolemic patients.

In Phase III studies, rosuvastatin was found to be more effective than other commonly used statins like atorvastatin, pravastatin, and simvastatin in improving lipid profiles, suggesting it could be a superior option for patients who struggle to reach target LDL-C levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new statin: a new standard. Olsson, AG.[2023]

Statin therapy has been shown to significantly reduce the risk of ischemic cardiovascular events and may even lower mortality within the first year of treatment, based on evidence from landmark trials.

Patients with moderately elevated cholesterol levels can safely benefit from statin treatment, as it is well tolerated and can prevent serious clinical events related to coronary artery disease when aggressive therapy is applied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Best practice--ongoing polemics. Paoletti, R., Bellosta, S.[2019]

Statins, such as atorvastatin and simvastatin, are highly effective in lowering cholesterol levels by inhibiting cholesterol synthesis in the liver, which helps reduce the risk of coronary heart disease (CHD).

The article reviews the pharmacological data of both established and novel statins, highlighting that differences in their pharmacokinetics may contribute to varying levels of toxicity and adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), including rosuvastatin and pitavastatin. Igel, M., Sudhop, T., von Bergmann, K.[2022]

Statins have been proven effective in improving lipid levels and significantly reducing the risk of atherosclerotic coronary artery disease (CAD), which leads to lower morbidity and mortality rates associated with CAD.

While statins are generally well tolerated, there are safety concerns regarding potential adverse effects on muscles, liver, kidneys, and the nervous system, with some risks being well-documented and others remaining speculative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin safety: an overview and assessment of the data--2005. Bays, H.[2022]

Recent research has identified new genetic factors linked to dyslipidemias, such as LDLR-associated protein and proprotein convertase subtilisin-like kexin type 9, which play crucial roles in cholesterol metabolism and could inform future treatments for coronary heart disease (CHD).

While intensive statin therapy can lower LDL cholesterol and potentially reduce cardiovascular risks, it also carries risks of side effects like myopathy and liver damage, highlighting the need for careful consideration of the risk-benefit ratio for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on dyslipidemia. Garg, A., Simha, V.[2007]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The lower the better? Reviewing the evidence for more aggressive cholesterol reduction and goal attainment. [2019]

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

Treating to New Targets (TNT) Study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit? [2019]

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

A new statin: a new standard. [2023]

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

Estimated number and percentage of US adults with atherosclerotic cardiovascular disease recommended add-on lipid-lowering therapy by the 2018 AHA/ACC multi-society cholesterol guideline. [2023]

5. Ireland pubmed.ncbi.nlm.nih.gov

Best practice--ongoing polemics. [2019]

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

Pharmacology of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), including rosuvastatin and pitavastatin. [2022]

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

Statin safety: an overview and assessment of the data--2005. [2022]

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

Update on dyslipidemia. [2007]

9. Georgia (Republic) pubmed.ncbi.nlm.nih.gov

[Clinical efficacy and safety of Zo-20 in patients with ischemic heart disease]. [2013]

10. Brazil pubmed.ncbi.nlm.nih.gov

[An evaluation of the efficacy and safety of pravastatin in patients with primary hypercholesterolemia. A Brazilian open multicenter study]. [2013]