AZD0780 for High Cholesterol

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of a new drug, AZD0780, for individuals with high cholesterol, specifically high LDL (the "bad" cholesterol). Researchers aim to assess the drug's tolerance and behavior in the body when administered alone or with another cholesterol medication, rosuvastatin. The trial includes several groups exploring various doses and combinations. It is open to healthy adults with manageable cholesterol levels and no major health issues. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that AZD0780 is likely to be safe for humans?

Research has shown that AZD0780 is generally safe and well-tolerated. Studies have found that it can be taken without concerns about food interactions. In individuals with high cholesterol, AZD0780 demonstrated a good safety record, with most participants not experiencing serious side effects. These results from earlier studies suggest that AZD0780 could be a promising option for managing cholesterol. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for high cholesterol, like statins, work by blocking a substance your body needs to make cholesterol. But AZD0780 offers a fresh approach by potentially targeting different pathways to lower cholesterol levels. Researchers are excited about AZD0780 because it might be used in combination with existing treatments like rosuvastatin to enhance efficacy, potentially providing a more robust solution for managing high cholesterol. This novel mechanism could mean fewer side effects and a more effective treatment for patients who don't respond well to current options.

What evidence suggests that this trial's treatments could be effective for high cholesterol?

Research has shown that AZD0780 is a pill that lowers "bad" cholesterol (LDL-C) in the blood. In earlier studies, participants who took AZD0780 experienced significant reductions in their LDL-C levels, with results varying by dose. This trial will evaluate different doses of AZD0780, with some participants receiving a placebo for comparison. Most participants tolerated the treatment well in previous studies, experiencing no serious side effects. This makes AZD0780 a promising option for lowering cholesterol levels. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/AZD0780-a-novel-oral-PCSK9-inhibitor-demonstrated-significant-LDL-cholesterol-LDL-C-reduction-in-PURSUIT-Phase-IIb-trial.html

AZD0780, a novel oral PCSK9 inhibitor, demonstrated ... Positive results from the PURSUIT Phase IIb trial for AstraZeneca's AZD0780 demonstrated a statistically significant low-density lipoprotein ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40167413/

An Oral PCSK9 Inhibitor for Treatment of ... AZD0780 demonstrated robust, dose-dependent reductions in LDL-C with a favorable safety and tolerability profile supporting further ...

3. jacc.org jacc.org/doi/10.1016/j.jacc.2025.03.499

An Oral PCSK9 Inhibitor for Treatment of ... Broadly speaking, AZD0780 led to lipid-lowering effects that reflect expectations for an effective inhibitor of PCSK9 with peak LDL-C effects of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07000136

A Phase III Study to Assess the Effect of AZD0780 on LDL- ... This is a study to evaluate the efficacy and safety of AZD0780 in adults with HeFH and elevated LDL-C, either with clinical ASCVD and LDL-C levels of 55 ...

5. atherosclerosis-journal.com atherosclerosis-journal.com/article/S0021-9150(25)00486-1/fulltext

Efficacy and safety of AZD0780, an oral small molecule ... The primary efficacy endpoint was percent change from baseline of LDL-C to week 12. Secondary endpoints included other lipids and hsCRP. Results: The study ...

6. atherosclerosis-journal.com atherosclerosis-journal.com/article/S0021-9150(24)01081-5/fulltext

AZD0780, the first oral small molecule PCSK9 inhibitor for ... Conclusions: AZD0780 was generally safe and well tolerated and may be dosed without regard to food. In treatment naïve hypercholesterolemic patients, the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05384262

NCT05384262 | A Study to Assess the Safety, Tolerability ... This study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD0780 following single and multiple dose administration ...