A Study to Assess the Efficacy, Safety and Tolerability of Different Doses of AZD0780 in Patients With Dyslipidemia (PURSUIT)

A Phase IIb, Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AZD0780 in Participants With Dyslipidemia

The primary purpose of this study is to measure the effect of different daily doses of AZD0780 on Low-Density Lipoprotein (LDL-C) levels compared with placebo in participants with dyslipidemia. The effect of AZD0780 versus placebo on other lipid parameters and inflammatory markers is also investigated. The concentration of AZD0780 in blood at specific timepoints is measured, and the safety and tolerability of AZD0780 will be evaluated. There is a follow-up after end of treatment, but expanded access is not available. The primary hypothesis is that at least one of the investigated doses of AZD0780 is superior to placebo in lowering LDL-C level, in percent change from baseline up to week 12.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: AZD0780; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 428
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4N 7L3
      • Research Site
    • Brampton, Ontario, Canada, L6S 0C6
      • Research Site
    • Cambridge, Ontario, Canada, N1R 6V6
      • Research Site
    • Concord, Ontario, Canada, L4K 4M2
      • Research Site
    • Guelph, Ontario, Canada, N1H 1B1
      • Research Site
    • Toronto, Ontario, Canada, M6G 1M2
      • Research Site
• Czechia
  • Benešov, Czechia, 256 01
    • Research Site
  • Brandýs nad Labem, Czechia, 250 01
    • Research Site
  • Brno, Czechia, 603 00
    • Research Site
  • Louny, Czechia, 440 01
    • Research Site
  • Náchod, Czechia, 547 01
    • Research Site
  • Prague, Czechia, 150 00
    • Research Site
  • Příbram, Czechia, 261 01
    • Research Site
  • Teplice, Czechia, 415 01
    • Research Site
  • Uherské Hradiště, Czechia, 68601
    • Research Site
• Denmark
  • Aarhus, Denmark, 8200
    • Research Site
  • Herning, Denmark, 7400
    • Research Site
  • Hvidovre, Denmark, 2650
    • Research Site
  • Svendborg, Denmark, 5700
    • Research Site
  • Viborg, Denmark, 8800
    • Research Site
• Hungary
  • Budapest, Hungary, 1027
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Orosháza, Hungary, 5900
    • Research Site
  • Pécs, Hungary, 7624
    • Research Site
• Japan
  • Chūōku, Japan, 103-0027
    • Research Site
  • Itabashi-ku, Japan, 173-0004
    • Research Site
• Slovakia
  • Bratislava, Slovakia, 831 03
    • Research Site
  • Brezno, Slovakia, 977 01
    • Research Site
  • Lučenec, Slovakia, 984 01
    • Research Site
  • Prešov, Slovakia, 080 01
    • Research Site
  • Rožňava, Slovakia, 048 01
    • Research Site
  • Svidník, Slovakia, 08901
    • Research Site
  • Trebišov, Slovakia, 075 01
    • Research Site
• Spain
  • A Coruña, Spain, 15006
    • Research Site
  • Barcelona, Spain, 08041
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • Ferrol, Spain, 15405
    • Research Site
  • Santiago(A Coruña), Spain, 15706
    • Research Site
  • Seville, Spain, 41004
    • Research Site
  • Seville, Spain, 41013
    • Research Site
  • Seville, Spain, 41071
    • Research Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Research Site
  • California
    • Lincoln, California, United States, 95648
      • Research Site
    • Palm Springs, California, United States, 92262
      • Research Site
    • Santa Ana, California, United States, 92704
      • Research Site
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Research Site
    • Hialeah, Florida, United States, 33012
      • Research Site
    • Inverness, Florida, United States, 34452
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Research Site
  • New York
    • New Windsor, New York, United States, 12553
      • Research Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Research Site
  • Texas
    • San Marcos, Texas, United States, 78666
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males, and females of non-childbearing potential 18 to 75 years of age, inclusive, at the time of signing the informed consent.
• Participants with a fasting low-density lipoprotein cholesterol (LDL-C) higher than or equal to 70 mg/dL (1.8 mmol/L) and lower than 190 mg/dL (4.9 mmol/L) at screening.
• Participants with fasting triglycerides lower than 400 mg/dL (lower than 4.52 mmol/L) at screening.
• Should be receiving moderate or high-intensity statin therapy for more than or equal to 2 months prior to screening.
• There should be no planned medication or dose change during study participation.
• Body mass index at or above 19.0 kg/m^2.

Exclusion Criteria:

• History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any uncontrolled or serious disease, or any medical (e.g., known major active infection or major hematological, renal, metabolic, gastrointestinal, respiratory, or endocrine dysfunction) or surgical condition that, in the opinion of the investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk.
• Poorly controlled type 2 diabetes mellitus, defined as hemoglobin A1c (HbA1c) greater than 10 percent at screening.
• Acute ischemic cardiovascular event in the last 12 months.
• Heart failure with New York Heart Association (NYHA) Class III-IV.
• Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in-situ, or Stage 1 prostate carcinoma) within the last 10 years.
• Recipient of any major organ transplant, e.g., lung, liver, heart, bone marrow, renal.
• LDL or plasma apheresis within 12 months prior to randomization.
• Uncontrolled hypertension.
• Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; AZD0780, Dose 1	Drug: AZD0780; AZD0780 administered orally, once daily for 12 weeks
Experimental: Arm B; AZD0780, Dose 2	Drug: AZD0780; AZD0780 administered orally, once daily for 12 weeks
Experimental: Arm C; AZD0780, Dose 3	Drug: AZD0780; AZD0780 administered orally, once daily for 12 weeks
Experimental: Arm D; AZD0780, Dose 4	Drug: AZD0780; AZD0780 administered orally, once daily for 12 weeks
Placebo Comparator: Arm E; Placebo, matched for appearance	Drug: Placebo; Placebo administered orally, once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12	Percent change was calculated as (Week 12 LDL-C - Baseline LDL-C) / Baseline LDL-C * 100. Negative values indicate reduction in LDL-C. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.	From first day of treatment up to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12	Percent change was calculated as (Week 12 LDL-C - Baseline LDL-C) / Baseline LDL-C * 100. Negative values indicate reduction in LDL-C. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.	From first day of treatment up to week 12
Percent Change From Baseline of Total Cholesterol at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.	From first day of treatment up to week 12
Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.	From first day of treatment up to week 12
Percent Change From Baseline of Triglycerides at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.	From first day of treatment up to week 12
Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.	From first day of treatment up to week 12
Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.	From first day of treatment up to week 12
Percent Change From Baseline of Apolipoprotein A1 at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.	From first day of treatment up to week 12
Percent Change From Baseline of Apolipoprotein B at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.	From first day of treatment up to week 12
Percent Change From Baseline of Total Cholesterol at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.	From first day of treatment up to week 12
Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.	From first day of treatment up to week 12
Percent Change From Baseline of Triglycerides at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.	From first day of treatment up to week 12
Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.	From first day of treatment up to week 12
Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.	From first day of treatment up to week 12
Percent Change From Baseline of Apolipoprotein A1 at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.	From first day of treatment up to week 12
Percent Change From Baseline of Apolipoprotein B at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.	From first day of treatment up to week 12
Percent Change From Baseline of Lipoprotein-a at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only.	From first day of treatment up to week 12
Percent Change From Baseline of Remnant Cholesterol at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only.	From first day of treatment up to week 12
Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12	Percent change was calculated as (Week 12 value - Baseline value) / Baseline value * 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only.	From first day of treatment up to week 12
AZD0780 Plasma Concentrations Summarized by Sampling Timepoint	Geometric mean plasma concentration; LLOQ = 0.01 umol/L; BLQ values are handled as Not Quantified (NQ)	From week 1 up to week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	Assessment of safety and tolerability of AZD0780 compared to placebo.	From first day of treatment up to week 14

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: AstraZeneca K.K.

Publications and helpful links

General Publications

• Koren MJ, Vega RB, Agrawal N, Xu Y, Barbour AM, Yu H, Wallerstedt E, Carter D, Middlemiss J, Twaddle L, McCarthy MC, Rosenmeier JB. An Oral PCSK9 Inhibitor for Treatment of Hypercholesterolemia: The PURSUIT Randomized Trial. J Am Coll Cardiol. 2025 Jun 3;85(21):1996-2007. doi: 10.1016/j.jacc.2025.03.499. Epub 2025 Mar 31.

Helpful Links

• Redacted CSP
• Redacted SAP
• Redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2024
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: December 8, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 3, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Low-Density Lipoprotein Cholesterol; Dyslipidemia,
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Dyslipidemias
• Other Study ID Numbers: D7960C00006; 2023-506197-12-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No