AZD0780 for Drug Interaction Study

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Anticonvulsants, Enzyme inducers, PCSK9 inhibitors

Disqualifiers: Gastrointestinal disease, Liver disease, Drug abuse, 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 explores how the new drug AZD0780 interacts with other medications. Researchers aim to understand how the body processes AZD0780 when taken alone and with drugs like itraconazole, carbamazepine, midazolam, and a combination of EE and LNG (types of hormonal birth control). The study targets healthy adults without serious health issues that might affect medication processing. Participants will take AZD0780 in various combinations over several periods to observe its effects alongside these other medications. As a Phase 1 trial, this research focuses on understanding the treatment's function 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?

The trial requires participants to stop taking any prescribed or nonprescribed medications, including hormone replacement therapy, antacids, and herbal remedies, for at least 2 weeks before starting the study. This means you will need to stop your current medications during this period.

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

Research has shown that AZD0780 has been studied for safety and tolerability. In earlier studies, patients received varying doses of AZD0780, and researchers observed its effects. So far, it has demonstrated a consistent and predictable response in the body, acting as expected without surprises. No evidence suggests that food affects the drug's absorption, which is a positive sign.

However, as this is a Phase 1 trial, it remains early in the testing process. Phase 1 marks the first stage of testing a new treatment in humans, so safety information is limited. This phase primarily focuses on ensuring the treatment's safety before testing it in larger groups. No major safety issues have been reported in the studies conducted so far, but more data is needed to confirm its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD0780 because it offers a new way to understand how different drugs interact with one another. Unlike standard treatments that focus solely on their individual effects, AZD0780 is being tested in combination with common medications like midazolam, EE and LNG, itraconazole, and carbamazepine to explore how these combinations work together. This approach could unveil potential interactions, leading to safer and more effective medication regimens in the future. By focusing on drug interactions, AZD0780 aims to improve patient outcomes by ensuring that combinations of medications are both safe and effective.

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

Research has shown that AZD0780, a new type of pill, can significantly lower LDL cholesterol, often referred to as "bad" cholesterol. One study found that AZD0780 reduced LDL cholesterol levels by 50.7% when combined with standard cholesterol-lowering drugs called statins. This reduction is comparable to other drugs in the same category, known for their cholesterol-lowering abilities. Most participants tolerated the treatment well, experiencing no major side effects. These results suggest that AZD0780 could effectively manage cholesterol levels. In this trial, participants will receive AZD0780 alongside other drugs such as midazolam, EE and LNG, itraconazole, or carbamazepine to study potential drug interactions. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 18 to 75 who are interested in helping study the effects of a new cholesterol medication, AZD0780. Participants should not have dyslipidemia or high cholesterol.

Inclusion Criteria

Provision of signed and dated, written informed consent prior to any study-specific procedures

I have tested negative for pregnancy before starting the trial.

I am a woman who cannot become pregnant.

Exclusion Criteria

I have recently used experimental drugs.

I have no conditions that affect how drugs are broken down in my body.

I have not donated blood or plasma recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4-5 weeks

Treatment Part 1

Participants receive AZD0780 alone and in combination with itraconazole

3-4 weeks

In-patient stay from Day -1 to Day 24

Treatment Part 2

Participants receive AZD0780 alone and in combination with carbamazepine

5-6 weeks

In-patient stay from Day -1 to Day 37

Treatment Part 3

Participants receive AZD0780 alone and in combination with midazolam

2-3 weeks

In-patient stay from Day -1 to Day 12

Treatment Part 4

Participants receive AZD0780 alone and in combination with EE and LNG

3-4 weeks

In-patient stay from Day -1 to Day 22

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

1 visit (in-person) 7 to 14 days post-discharge

What Are the Treatments Tested in This Trial?

Interventions

• AZD0780

Trial Overview The study is looking at how the body processes a new drug called AZD0780 when taken alone and alongside other medications, Itraconazole and Carbamazepine. It's an open-label trial where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Midazolam Cohort Experimental Treatment 2 Interventions

* All participants will receive 10 single doses of AZD0780 dose 2 and 2 doses of midazolam. On midazolam dosing days, participants will receive midazolam under fasted conditions. * This part will consist of Period 1 (midazolam administration only), Period 2 (AZD0780 administration only), and Period 3 (AZD0780 + midazolam administration).

Group II: Itraconazole Cohort Experimental Treatment 2 Interventions

* All participants will receive 2 single doses of dose 1 of AZD0780 and 14 doses of itraconazole, under fed conditions. * This part will consist of Period 1 (AZD0780 administration only), Period 2 (itraconazole administration only), and Period 3 (AZD0780 + itraconazole administration).

Group III: EE and LNG Cohort Experimental Treatment 2 Interventions

* All participants will receive 15 single doses of AZD0780 dose 2 and 2 doses of EE and LNG. On EE and LNG dosing days, participants will receive EE and LNG under fasted conditions. * This part will consist of Period 1 (EE and LNG administration only), Period 2 (AZD0780 administration only), and Period 3 (AZD0780 + EE and LNG administration).

Group IV: Carbamazepine Cohort Experimental Treatment 2 Interventions

* All participants will receive 2 single doses of dose 1 of AZD0780 and 6 doses of 100 mg, 6 doses of 200 mg, and 40 doses of 300 mg carbamazepine, under fed conditions. * This part will consist of Period 1 (AZD0780 administration only), Period 2 (carbamazepine administration only), and Period 3 (AZD0780 + carbamazepine administration)

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

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0735109725059078

An Oral PCSK9 Inhibitor for Treatment of ... The phase 2 PURSUIT study showed a favorable efficacy and safety profile of AZD0780, broadly comparable to other PCSK9 inhibitors, with the advantage of a once- ...

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

An Oral PCSK9 Inhibitor for Treatment of ... The phase 2 PURSUIT study showed a favorable efficacy and safety profile of AZD0780, broadly comparable to other PCSK9 inhibitors, with the ...

3. 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 ... AZD0780 was generally well tolerated, and adverse events (AEs) were comparable between the total AZD0780 treatment groups (38.2%) and placebo ( ...

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. pharmacytimes.com pharmacytimes.com/view/azd0780-novel-oral-pcsk9-inhibitor-demonstrates-major-ldl-cholesterol-reductions

AZD0780, Novel Oral PCSK9 Inhibitor, Demonstrates ... AZD0780 achieved a 50.7% reduction in LDL-C levels when combined with standard statin therapy, showing consistent efficacy across different ...

6. 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 ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/analyst-comment/acc-2025-azd0780-ldl-c/

ACC 2025: AZD0780 shows significant LDL-C reduction in ... AZD0780 30mg taken daily demonstrated robust, dose-dependent, placebo-adjusted reductions in LDL-C from baseline to week 12 by up to 50.7%.

8. astrazeneca.com astrazeneca.com/content/astraz/media-centre/medical-releases/azd0780-an-oral-pcsk9-inhibitor-demonstrated-significant-ldl-c-reduction-on-top-of-statin-in-phase-i-trial.html

AZD0780, an oral PCSK9 inhibitor demonstrated ... AZD0780 demonstrated a statistically significant reduction of 52% (95%CI: -57, -45) in LDL-C levels on top of rosuvastatin treatment, with 78% ...