AZD0780 + Ezetimibe for High Cholesterol

No longer recruiting at 2 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must be taking: Ezetimibe

Must not be taking: PCSK9 inhibitors

Disqualifiers: Gastrointestinal, Hepatic, Renal, others

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the new treatment, AZD0780, works when combined with the cholesterol-lowering drugs ezetimibe, rosuvastatin, or bempedoic acid. The study targets individuals with untreated high cholesterol, specifically those with LDL cholesterol levels between 100 mg/dL and 190 mg/dL. Those managing cholesterol through diet but still experiencing high levels might be suitable for this trial. Participants will receive different combinations of these medications or a placebo over a four-week period to compare effectiveness. 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 treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken any lipid-lowering therapy or AZD0780 in the 3 months before the trial, or PCSK9 inhibitors in the last 12 months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that AZD0780 is safe and well-tolerated, meaning most participants did not experience serious side effects. Research indicates that AZD0780, when combined with other cholesterol-lowering drugs like ezetimibe, rosuvastatin, or bempedoic acid, effectively lowers bad cholesterol (LDL-C) with minimal negative effects.

Although the study did not focus on side effects, evidence suggests that AZD0780 is generally well-tolerated. As this is an early-stage study primarily examining safety, any major issues would likely have been identified. Prospective trial participants should discuss any concerns with healthcare professionals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD0780 for high cholesterol because it offers a novel approach by targeting cholesterol absorption in the intestines differently from traditional statins like atorvastatin or rosuvastatin, which mainly focus on reducing cholesterol production in the liver. AZD0780 is combined with ezetimibe, which already inhibits intestinal cholesterol absorption, potentially enhancing cholesterol reduction beyond current options. This dual mechanism could provide a more comprehensive strategy for managing high cholesterol, especially for patients who may not respond fully to existing treatments.

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

This trial will evaluate the effectiveness of various combinations of cholesterol-lowering treatments. Participants in one arm will receive AZD0780 combined with ezetimibe, which studies have shown can lower "bad" LDL cholesterol by up to 50.7%. Another arm will test the combination of AZD0780, ezetimibe, and rosuvastatin, a commonly used cholesterol-lowering drug, which has shown promising results in further reducing total cholesterol. Additionally, an optional cohort will receive AZD0780, ezetimibe, and bempedoic acid, another drug effective in improving heart health. These combinations aim to address high cholesterol in different ways, potentially offering better results for patients. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for healthy adults with high LDL-C (bad cholesterol) levels. Participants must be over 18, weigh at least 50 kg, and have a BMI above 18. Women must not be pregnant or able to become pregnant, while sexually active men need to use contraception. Cholesterol and triglyceride levels are specified for eligibility.

Inclusion Criteria

My LDL cholesterol is between 100 and 190 mg/dL.

I am not pregnant, as confirmed by a blood test.

I am a woman who cannot become pregnant because I am postmenopausal or have been surgically sterilized.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Run-in

Participants undergo a run-in period to stabilize conditions before treatment

4 weeks

Treatment

Participants receive AZD0780 or placebo in combination with ezetimibe, ezetimibe/rosuvastatin, or ezetimibe/bempedoic acid

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• AZD0780

Trial Overview The study tests AZD0780's effects on lowering bad cholesterol when combined with ezetimibe alone or alongside rosuvastatin or bempedoic acid. It compares these combinations against a placebo to evaluate safety, tolerability, and effectiveness in managing high cholesterol.

How Is the Trial Designed?

Group I: Rosuvastatin + Ezetimibe + AZD0780 Experimental Treatment 3 Interventions

Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks.

Group II: Ezetimibe + AZD0780 Experimental Treatment 2 Interventions

Participants will receive ezetimibe 10 mg and AZD0780 once daily (QD) for 4 weeks.

Group III: Bempedoic Acid + Ezetimibe + AZD0780 (Optional Cohort) Experimental Treatment 3 Interventions

Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks.

Group IV: Ezetimibe + Placebo Placebo Group 2 Interventions

Participants will receive ezetimibe 10 mg and placebo QD for 4 weeks.

Group V: Rosuvastatin + Ezetimibe + Placebo Placebo Group 3 Interventions

Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and placebo QD for 4 weeks.

Group VI: Bempedoic Acid + Ezetimibe + Placebo (Optional Cohort) Placebo Group 3 Interventions

Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and placebo QD for 4 weeks.

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

Published Research Related to This Trial

In a study of 374,786 adults aged 66 and older who experienced a myocardial infarction, only 1.9% initiated ezetimibe and 0.4% initiated a PCSK9 inhibitor, indicating low uptake of these recommended treatments for very high-risk ASCVD patients.

The analysis revealed significant disparities in treatment initiation based on race and sex, with non-Hispanic Black patients showing lower rates of initiation for both ezetimibe and PCSK9 inhibitors compared to non-Hispanic White patients, and women being more likely than men to start these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Race/ethnic and sex differences in the initiation of non-statin lipid-lowering medication following myocardial infarction. Colvin, CL., Poudel, B., Bress, AP., et al.[2022]

Ezetimibe is a new lipid-lowering medication that works by blocking the absorption of cholesterol in the intestines, and it is particularly effective when used alongside statins to further reduce cholesterol levels in patients with high cholesterol.

The combination of ezetimibe and statins significantly lowers total and LDL cholesterol, improving the chances of patients reaching recommended cholesterol targets, although further large-scale studies are needed to confirm its impact on reducing heart disease risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ezetimibe (Ezetrol)]. Scheen, AJ.[2015]

Ezetimibe, a cholesterol absorption inhibitor, was found to be safe and well tolerated in a study involving eight healthy male volunteers who received a single 20-mg dose, with no adverse events reported.

The drug was rapidly absorbed and extensively metabolized, primarily through glucuronidation, with significant enterohepatic recycling, indicating a complex metabolic pathway that aids in its efficacy for treating primary hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Patrick, JE., Kosoglou, T., Stauber, KL., et al.[2022]

In a study involving 17,999 post-acute coronary syndrome patients over 6 years, adding ezetimibe to statin therapy significantly reduced the risk of cardiovascular events, regardless of whether patients had low-density lipoprotein cholesterol (LDL-C) levels above or below 70 mg/dL.

The benefits of ezetimibe were consistent across different baseline LDL-C levels, indicating that intensive lipid-lowering therapy is effective even for patients with LDL-C <70 mg/dL, without any significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Low-Density Lipoprotein Cholesterol and Clinical Outcomes of Combining Ezetimibe With Statin Therapy in IMPROVE-IT. Oyama, K., Giugliano, RP., Blazing, MA., et al.[2022]

In a meta-analysis of 13 studies involving 5080 patients, adding ezetimibe to statin therapy resulted in a significantly greater reduction in LDL cholesterol levels compared to simply doubling the statin dose, with a weighted mean difference of -15.3%.

Patients receiving the ezetimibe-statin combination were more likely to achieve their LDL cholesterol treatment goals, with an odds ratio of 2.45, indicating that this combination therapy is more effective than increasing statin dosage alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis. Mikhailidis, DP., Lawson, RW., McCormick, AL., et al.[2022]

Ezetimibe 10 mg/day significantly reduced plasma sitosterol levels by 43.9% and campesterol levels by 50.8% over two years in patients with homozygous sitosterolemia, demonstrating its long-term efficacy.

The treatment was well tolerated, with no significant adverse effects reported, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open-label extension study. Lütjohann, D., von Bergmann, K., Sirah, W., et al.[2015]

PCSK9 inhibitors and ezetimibe are effective in reducing cardiovascular events, providing a strong option for patients at high risk of heart disease.

The clinical practice guideline offers risk-stratified recommendations, helping healthcare providers tailor treatment plans based on individual patient risk levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for use of ezetimibe and/or PCSK9 inhibitors in patients with elevated LDL-C. Kelsey, MD., Newby, LK.[2022]

In a study of 827 patients with primary hypercholesterolemia, ezetimibe 10 mg/day significantly reduced low-density lipoprotein cholesterol (LDL-C) by an average of 17.7% compared to a 0.8% increase with placebo, demonstrating its efficacy in lowering cholesterol levels.

Ezetimibe was well tolerated and had a safety profile similar to placebo, without affecting lipid-soluble vitamins or cortisol production, suggesting it is a safe option for managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Knopp, RH., Gitter, H., Truitt, T., et al.[2019]

A systematic review of 48 randomized controlled trials involving 28,444 participants found that ezetimibe is not associated with significant adverse effects, such as cancer, fractures, or gastrointestinal issues, indicating it is a safe option for lipid-lowering treatment.

Ezetimibe showed little to no difference in adverse events compared to placebo and other lipid-lowering agents, suggesting its efficacy in lowering lipids without increasing the risk of undesirable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ezetimibe in lipid-lowering treatment: systematic review and meta-analysis of randomised controlled trials and cohort studies. Wang, Y., Zhan, S., Du, H., et al.[2023]

In a study of 450 patients with coronary heart disease who were not meeting LDL cholesterol goals on atorvastatin, co-administering ezetimibe significantly increased the percentage of patients achieving the LDL-C target of ≤2.6 mmol/l (81.3% vs. 21.8% with placebo).

The combination of ezetimibe and atorvastatin resulted in greater reductions in LDL-C and other cholesterol markers, while also being well tolerated and showing a safety profile similar to atorvastatin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease. Cruz-Fernández, JM., Bedarida, GV., Adgey, J., et al.[2018]

In a study involving 538 patients with primary hypercholesterolemia, the combination of ezetimibe 10 mg and pravastatin resulted in significant reductions in LDL cholesterol (LDL-C) by 34-41% and triglycerides (TG) by 21-23% compared to pravastatin alone.

The combined treatment was well tolerated, showing a safety profile similar to that of pravastatin alone and placebo, indicating it is a safe and effective option for managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Melani, L., Mills, R., Hassman, D., et al.[2019]

Ezetimibe significantly reduces low-density lipoprotein cholesterol (LDL-C) levels in HIV-positive patients with hyperlipidaemia, with a net change of approximately -23.56 mg/dL based on randomized controlled trials and -23.89 mg/dL in single-arm trials.

In addition to lowering LDL-C, ezetimibe also leads to significant reductions in total cholesterol (TC) and triglycerides (TG), making it a potential treatment option for HIV patients with elevated lipid levels, especially when statins cannot be used due to drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of ezetimibe in human immunodeficiency virus patients treated for hyperlipidaemia: a systematic review and meta-analysis. Nirmala, N., Avendano, EE., Morin, RA.[2022]

In the PRECISE-IVUS trial involving 246 patients, the combination of atorvastatin and ezetimibe significantly reduced coronary plaque volume in patients who had prior statin therapy, indicating enhanced antiatherosclerotic effects in this group.

Patients with statin pretreatment showed a greater reduction in atheroma volume with the atorvastatin/ezetimibe combination compared to atorvastatin alone, suggesting that this combination may be particularly beneficial for those who do not respond adequately to statins alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic effect of ezetimibe addition on coronary atheroma regression in patients with prior statin therapy: Subanalysis of PRECISE-IVUS trial. Tsujita, K., Yamanaga, K., Komura, N., et al.[2018]

In a phase III trial involving 109 patients with hypercholesterolemia, the fixed-dose combination of pitavastatin and ezetimibe (K-924) significantly reduced LDL cholesterol levels by an average of 30.3% after 52 weeks, with 91.8% of patients achieving their LDL-C management target.

K-924 was found to be well-tolerated, with only one reported adverse drug reaction, indicating that it is a safe option for intensifying cholesterol-lowering therapy without adding more medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Safety of K-924 Pitavastatin/Ezetimibe Fixed-dose Combination in Patients with Hypercholesterolemia: A Phase III, Multi-center, Open-label Trial. Ako, J., Yokote, K., Tsujita, K., et al.[2023]

A study involving 59 healthy Chinese volunteers demonstrated that the test ezetimibe tablet is bioequivalent to Ezetrol® under both fasting and fed conditions, meeting the regulatory criteria for pharmacokinetic parameters like Cmax and AUC.

No severe adverse events were reported during the study, indicating that both formulations of ezetimibe are safe for use in the tested population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of Ezetimibe tablet versus Ezetrol®:an open-label, randomized, two-sequence crossover study in healthy Chinese subjects. Sun, F., Liu, Y., Li, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06742853

NCT06742853 | A Study to Investigate the ... The main aim of this study is to assess the effects of AZD0780 when added on top of ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.

2. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/AZN/pressreleases/33892859/astrazenecas-new-study-on-azd0780-potential-game-changer-for-cholesterol-treatment/

AstraZeneca's New Study on AZD0780: Potential Game- ... The study aims to evaluate the pharmacokinetics, safety, tolerability, and efficacy of the drug AZD0780 when combined with ezetimibe, ezetimibe/ ...

3. withpower.com withpower.com/trial/azd0780-ezetimibe-for-high-cholesterol-59587

AZD0780 + Ezetimibe for High Cholesterol In a meta-analysis of 13 studies involving 5080 patients, adding ezetimibe to statin therapy resulted in a significantly greater reduction in LDL cholesterol ...

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7960C00017

A Study to Investigate the Pharmacokinetics, Safety ... The main aim of this study is to assess the effects of AZD0780 when added on top of ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11755694/

Current and emerging PCSK9‐directed therapies to reduce ... In 2023, bempedoic acid was shown to reduce cardiovascular outcomes when studied in a randomized placebo‐controlled trial of nearly 14,000 patients with or at ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31357887/

Bempedoic acid plus ezetimibe fixed-dose combination in ... The bempedoic acid and ezetimibe fixed-dose combination significantly lowered low-density lipoprotein cholesterol versus placebo or other oral monotherapies.