Study to Evaluate the Efficacy and Safety of AZD4831 in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40% (ENDEAVOR)

A Randomised, Double-blind, Placebo-controlled, Multi-center Sequential Phase 2b and Phase 3 Study to Evaluate the Efficacy and Safety of AZD4831 Administered for Up to 48 Weeks in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40%

This is a randomised, double-blind, placebo-controlled, multi-center sequential phase 2b and Phase 3 study to evaluate the efficacy and safety of AZD4831 administered for up to 48 Weeks in participants with heart failure with left ventricular ejection fraction > 40%. The study will consist of 2 separate parts, Part A and Part B, approximately 660 participants will be randomised in Part A, 820 in Part B.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Other: Placebo; Drug: AZD4831

• Study Type: Interventional
• Enrollment (Actual): 711
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Research Site
  • Chermside, Australia, 4032
    • Research Site
  • Concord, Australia, 2139
    • Research Site
  • Frankston, Australia, 3199
    • Research Site
• Belgium
  • Aalst, Belgium, 9300
    • Research Site
  • Dendermonde, Belgium, 9200
    • Research Site
  • Hasselt, Belgium, 3500
    • Research Site
  • Huy, Belgium, 4500
    • Research Site
  • Kortrijk, Belgium, 8500
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Roeselare, Belgium, 8800
    • Research Site
• Brazil
  • Brasília, Brazil, 72145-450
    • Research Site
  • Campina Grande do Sul, Brazil, 83430000
    • Research Site
  • Campinas, Brazil, 13060-080
    • Research Site
  • Campinas, Brazil, 13092133
    • Research Site
  • Canoas, Brazil, 92425-020
    • Research Site
  • Curitiba, Brazil, 80730-150
    • Research Site
  • Porto Alegre, Brazil, 90035-903
    • Research Site
  • Ribeirão Preto, Brazil, 14051-140
    • Research Site
  • Ribeirão Preto, Brazil, 14026-020
    • Research Site
  • Rio de Janeiro, Brazil, 22061-080
    • Research Site
  • São Paulo, Brazil, 01228-200
    • Research Site
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Research Site
  • Pleven, Bulgaria, 5804
    • Research Site
  • Plovdiv, Bulgaria, 4003
    • Research Site
  • Sofia, Bulgaria, 1431
    • Research Site
  • Sofia, Bulgaria, 1784
    • Research Site
  • Sofia, Bulgaria, 1202
    • Research Site
  • Sofia, Bulgaria, 1407
    • Research Site
  • Sofia, Bulgaria, 1527
    • Research Site
  • Sofia, Bulgaria, 1309
    • Research Site
  • Sofia, Bulgaria, 1606
    • Research Site
  • Varna, Bulgaria, 9000
    • Research Site
• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1H 1B1
      • Research Site
    • Newmarket, Ontario, Canada, L3Y 2P6
      • Research Site
    • North York, Ontario, Canada, M9N 1W4
      • Research Site
    • Ottawa, Ontario, Canada, K1Y 4W7
      • Research Site
    • Toronto, Ontario, Canada, M6G 1M2
      • Research Site
    • Waterloo, Ontario, Canada, N2T 0C1
      • Research Site
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Research Site
    • Trois-Rivières, Quebec, Canada, G9A 4P3
      • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Broumov, Czechia, 55001
    • Research Site
  • Jaroměř, Czechia, 551 01
    • Research Site
  • Kolín, Czechia, 280 02
    • Research Site
  • Louny, Czechia, 440 01
    • Research Site
  • Pilsen, Czechia, 320 00
    • Research Site
  • Prague, Czechia, 110 00
    • Research Site
  • Prague, Czechia, 121 11
    • Research Site
  • Příbram, Czechia, 261 01
    • Research Site
  • Zlín, Czechia, 760 01
    • Research Site
• Denmark
  • Copenhagen, Denmark, 2300
    • Research Site
  • Copenhagen O, Denmark, 2100
    • Research Site
  • Hvidovre, Denmark, 2650
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Roskilde, Denmark, 4000
    • Research Site
  • Viborg, Denmark, 8800
    • Research Site
  • Århus N, Denmark, 8200
    • Research Site
• France
  • Bayonne, France, 64100
    • Research Site
  • Dijon, France, 21079
    • Research Site
  • La Tronche, France, 38043
    • Research Site
  • Le Coudray, France, 28630
    • Research Site
  • Montauban, France, 82017
    • Research Site
  • Montpellier, France, 34295
    • Research Site
  • Paris, France, 75010
    • Research Site
  • Paris, France, 75015
    • Research Site
  • Pierre-Bénite, France, 69495
    • Research Site
  • Rennes, France, 35033
    • Research Site
  • Saint-Brieuc, France, 22027
    • Research Site
  • Toulon, France, 83100
    • Research Site
  • Toulouse, France, 31059
    • Research Site
  • Tourcoing, France, 59208
    • Research Site
• Hungary
  • Balatonfüred, Hungary, 8230
    • Research Site
  • Budapest, Hungary, 1122
    • Research Site
  • Budapest, Hungary, 1096
    • Research Site
  • Nyíregyháza, Hungary, 4400
    • Research Site
• Japan
  • Fukui-shi, Japan, 910-8526
    • Research Site
  • Higashiohmi-shi, Japan, 527-8505
    • Research Site
  • Iwakuni-shi, Japan, 740-8510
    • Research Site
  • Kanazawa, Japan, 920-8650
    • Research Site
  • Kasugai-shi, Japan, 487-0016
    • Research Site
  • Kishiwada-shi, Japan, 596-0042
    • Research Site
  • Kure-shi, Japan, 737-0023
    • Research Site
  • Kyoto, Japan, 612-8555
    • Research Site
  • Matsumoto-shi, Japan, 390-8621
    • Research Site
  • Minamiku, Japan, 861-4193
    • Research Site
  • Nagano, Japan, 399-8695
    • Research Site
  • Naha, Japan, 902-8511
    • Research Site
  • Otaru-shi, Japan, 047-8510
    • Research Site
  • Sagamihara-shi, Japan, 252-5188
    • Research Site
  • Toshima-ku, Japan, 171-0014
    • Research Site
  • Ueda-shi, Japan, 386-8610
    • Research Site
  • Uwajima-shi, Japan, 798-8510
    • Research Site
  • Yokohama, Japan, 245-8575
    • Research Site
  • Ōita, Japan, 870-8511
    • Research Site
  • Ōmihachiman, Japan, 523-0082
    • Research Site
• Netherlands
  • 's-Hertogenbosch, Netherlands, 5223 GZ
    • Research Site
  • Amsterdam, Netherlands, 1081 HV
    • Research Site
  • Deventer, Netherlands, 7416 SE
    • Research Site
  • Heerlen, Netherlands, 6419 PC
    • Research Site
  • The Hague, Netherlands, 2545 AA
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-079
    • Research Site
  • Lublin, Poland, 20-044
    • Research Site
  • Rzeszów, Poland, 35-055
    • Research Site
  • Skierniewice, Poland, 96-100
    • Research Site
  • Tarnów, Poland, 33-100
    • Research Site
  • Tczew, Poland, 83-110
    • Research Site
  • Tychy, Poland, 43-100
    • Research Site
  • Warsaw, Poland, 04-749
    • Research Site
  • Warsaw, Poland, 02-758
    • Research Site
  • Warsaw, Poland, 02-677
    • Research Site
  • Wołomin, Poland, 05-200
    • Research Site
• Russia
  • Aramil, Russia, 624002
    • Research Site
  • Kemerovo, Russia, 650002
    • Research Site
  • Moscow, Russia, 121205
    • Research Site
  • Moscow, Russia, 119991
    • Research Site
  • Moscow, Russia, 121552
    • Research Site
  • Novosibirsk, Russia, 630055
    • Research Site
  • Perm, Russia, 614007
    • Research Site
  • Saint Petersburg, Russia, 195067
    • Research Site
  • Tver', Russia, 170036
    • Research Site
• Slovakia
  • Banská Bystrica, Slovakia, 974 01
    • Research Site
  • Bratislava, Slovakia, 821 07
    • Research Site
  • Brezno, Slovakia, 977 01
    • Research Site
  • Košice, Slovakia, 04022
    • Research Site
  • Košice, Slovakia, 044 24
    • Research Site
  • Nitra, Slovakia, 949 01
    • Research Site
  • Prešov, Slovakia, 080 01
    • Research Site
• Sweden
  • Gothenburg, Sweden, 413 45
    • Research Site
  • Jönköping, Sweden, 551 85
    • Research Site
  • Lund, Sweden, 222 21
    • Research Site
  • Norrköping, Sweden, 603 79
    • Research Site
  • Stockholm, Sweden, 118 83
    • Research Site
  • Stockholm, Sweden, 171 76
    • Research Site
  • Stockholm, Sweden, 18288
    • Research Site
  • Örebro, Sweden, 701 85
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 81362
    • Research Site
  • Kaohsiung City, Taiwan, 807
    • Research Site
  • Kaohsiung City, Taiwan, 833
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Taichung, Taiwan, 40201
    • Research Site
  • Tainan City, Taiwan, 70403
    • Research Site
  • Tainan City, Taiwan, 710
    • Research Site
  • Taipei, Taiwan, 100
    • Research Site
  • Taipei, Taiwan
    • Research Site
  • Taipei, Taiwan, 110
    • Research Site
  • Taoyuan District, Taiwan, 333
    • Research Site
• Turkey (Türkiye)
  • Eskişehir, Turkey (Türkiye), 26480
    • Research Site
  • Izmir, Turkey (Türkiye), 35340
    • Research Site
• United States
  • Alabama
    • Alexander City, Alabama, United States, 35010
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Research Site
  • California
    • Sacramento, California, United States, 95821
      • Research Site
  • Florida
    • Miami, Florida, United States, 33144
      • Research Site
    • Miami Beach, Florida, United States, 33140
      • Research Site
    • Ocala, Florida, United States, 34471
      • Research Site
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Research Site
    • Hazel Crest, Illinois, United States, 60429
      • Research Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71105
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63136
      • Research Site
  • New York
    • Buffalo, New York, United States, 14215
      • Research Site
    • New York, New York, United States, 10019
      • Research Site
    • Rosedale, New York, United States, 11422
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
    • Pinehurst, North Carolina, United States, 28374
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Research Site
    • Tullahoma, Tennessee, United States, 37388
      • Research Site
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Part A

1. ≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
2. Documented stable symptomatic HF (New York Heart Association Class II-IV) for at least 1 month at Screening (Visit 1) (transient HF in the setting of an MI does not qualify), with a medical history of typical symptoms of HF and receiving optimal therapy for HF as determined by the health-care physician.
3. LVEF > 40% at Screening (Visit 1). All participants will undergo a local echocardiogram at the Screening (Visit 1) with central reading to confirm the LVEF > 40% eligibility criteria before randomisation.
4. 6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 3). Difference in 6MWD between Screening and Randomisation must be < 50 meters.
5. KCCQ-TSS ≤ 90 points at Screening (Visit 1) and Randomisation (Visit 3)
6. NT-proBNP ≥ 250 pg/mL (sinus rhythm) or ≥ 500 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI ≤30 kg/m2.

NT-proBNP ≥ 200 pg/mL (sinus rhythm) or ≥ 400 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI > 30 kg/m2.

The ECG performed at Screening should be used for heart rhythm evaluation.

7.At least one of the following:

1. Structural heart disease, ie, LA enlargement and/or left ventricular hypertrophy at the echocardiogram performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width (diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LAVI > 34 mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness ≥ 1.1 cm or LVMI > 95 g/m2 in women and > 115 g/m2 in men.
2. Spectral tissue Doppler echocardiography - E/e' ratio (average of septal and lateral) ≥ 13 at rest at the echocardiogram performed at Screening (Visit 1).
3. Indirectly estimated elevation of PASP by TRmax velocity > 2.8 m/s (280 cm/s) (PASP > 35 mmHg) at the echocardiogram performed at Screening (Visit 1) OR directly measured pulmonary capillary wedge pressure > 15 mmHg at rest within the past 12 months or > 25 mmHg at exercise documented by right heart catheterisation within 12 months prior to Screening (Visit 1).

4. HF decompensation within 6 months before Randomisation (Visit 3), defined as hospitalisation for HF or IV diuretic treatment for HF during an urgent, unscheduled visit without hospitalisation.

   8.Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2

   9.Male or female of non-childbearing potential.

   Part B

   1. Participant must be ≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
   2. Documented diagnosis of symptomatic HF (NYHA class II-IV) at Screening (Visit 1), and a medical history of typical symptoms/signs of heart failure ≥ 6 weeks before Screening (Visit 1), and receiving optimal therapy for HF as determined by the health-care physician, with at least intermittent need for diuretic treatment.

   3. LVEF >40% and evidence of structural heart disease (ie, left ventricular hypertrophy or

      left atrial enlargement [defined by at least one of the following:LA enlargement and/or left ventricular hypertrophy at the echocardiogram

      performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width

      (diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LAVI > 34

      mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness ≥ 1.1 cm or

      LVMI > 95 g/m2 in women and > 115 g/m2 in men.]) documented by the most recent echocardiogram, or cardiac

      magnetic resonance imaging within the last 12 months prior to Screening (Visit 1). If no

      echocardiogram is available, it can be performed at Screening (Visit 1).

   4. 6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 2). Difference in 6MWD between Screening and Randomisation must be < 50 meters
   5. KCCQ-TSS ≤ 90 points at Screening (Visit 1) and Randomisation (Visit 2).
   6. NT-proBNP ≥ 250 pg/mL (sinus rhythm) or ≥ 500 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI ≤ 30 kg/m2. NT-proBNP ≥ 200 pg/mL (sinus rhythm) or ≥ 400 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI > 30 kg/m2. The ECG performed at Screening should be used for heart rhythm evaluation
   7. Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2
   8. Male or female of non-childbearing potential.

   Exclusion Criteria:

   Part A

   1 eGFR < 30 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration formula) at Screening (Visit 1).

   2. Systolic blood pressure < 90 mmHg or ≥ 160 mmHg if not on treatment with ≥ 3 blood pressure lowering medications or ≥ 180 mmHg irrespective of treatments at Randomisation

   3. Heart rate > 110 bpm or < 50 bpm at Randomisation

   4. Life expectancy < 3 years due to other reasons than cardiovascular disease.

   5. History or ongoing allergy/hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria).

   6. Presence of any disease or condition rather than HF constituting the main reason for limiting the ability to exercise/reduced exercise capacity.

   7. Current decompensated HF and/or NT-proBNP > 5000 pg/mL at Screening (Visit 1)

   8. Documented history of ejection fraction ≤ 40%.i.e. HF with recovered ejection fraction. Transient ejection fraction decrease e.g. in the setting of an MI does not apply

   9. Any planned cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).

   10. Any cardiac event (eg, myocardial infarction, unstable angina), coronary revascularisation (percutaneous coronary intervention or coronary artery bypass grafting), ablation of atrial fibrillation/flutter, valve repair/replacement, implantation of a cardiac resynchronisation therapy device within 12 weeks prior to Screening (Visit 1) or between Screening and Randomisation. Patients who underwent a successful atrial fibrillation/flutter cardioversion, can be enrolled in the study after 4 weeks.

   14. Hb < 110 g/L (male) and < 100 g/L (female) or iron-deficiency with/without anaemia requiring ongoing or planned IV iron treatment.

   15. Participants with hyperthyroidism, uncontrolled hypothyroidism (including but not limited to TSH ≥10 mIU/mL), or any clinically significant thyroid disease as judged by the investigator.

   18. ALT or AST ≥ 2 × ULN at Screening (Visit 1).

   19. Pulmonary arterial hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (ie, requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory support within 12 months prior to Screening (Visit 1).

   20. Any active infection requiring oral, intravenous or intramuscular treatment at Screening (Visit 1) and/or at Randomisation.

   23 Any signs or confirmation of COVID-19 infection:

   • Suspected (as judged by PI) or confirmed COVID-19 within the last 2 weeks prior to Screening (Visit 1) or at Randomisation.

   • Hospitalisation for COVID-19 within the last 12 weeks prior to Screening (Visit 1).

     24. Any concomitant medications known to be a potent CYP3A4 inducers or inhibitors, eg, itraconazole, rifampicin, clarithromycin, or propylthiouracil

     29. Previous enrolment and randomisation in the present study. (Participants who where screened and screen failed and not randomised in Part A can be screened for possible entry to Part B).

   All exclusion criteria in Part A are applicable to Part B with the following exceptions:

   Exclusion criteria 4; 19

   Exclusion Criteria specific for Part B only [criteria numeration for Part B]

   4. Life expectancy < 2 years due to other reasons than cardiovascular disease.

   11. HF due to any of the following: known infiltrative cardiomyopathy (eg, amyloid, sarcoid, lymphoma, endomyocardial fibrosis), active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), or uncorrected primary valvular disease.

   18. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (ie, requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory support within 12 months prior to Screening [Visit 1]).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A 2.5 mg; AZD4831 2.5 mg	Drug: AZD4831; AZD4831
Experimental: Part A 5 mg; AZD4831 5 mg	Drug: AZD4831; AZD4831
Placebo Comparator: Part A Placebo; Placebo	Other: Placebo; Placebo
Experimental: Part B Dose based on Part A; AZD4831 Dose based on Part A	Drug: AZD4831; AZD4831
Placebo Comparator: Part B Placebo; Placebo	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kansas City Cardiomyopathy Questionnaire -Total Symptom Score	Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 16 weeks compared with placebo Part A. The score ranges from 0 to 100, where a higher score represents a better patient outcome	Baseline - 16 weeks
Six Minute Walk Distance	Six Minute Walk Distance change from baseline at 16 weeks compared with placebo Part A	Baseline - 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kansas City Cardiomyopathy Questionnaire-Total Symptom Score	Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 24 and 48 weeks compared with placebo Part A. The score ranges from 0 to 100, where a higher score represents a better patient outcome.	Baseline - 24 and 48 weeks
Six Minute Walk Distance	Six Minute Walk Distance change from baseline at 24 and 48 weeks compared with placebo Part A	Baseline - 24 and 48 weeks
Interleukin 6 (IL-6)	IL-6 change from baseline at 16, 24, and 48 weeks compared with placebo Part A	Baseline - 16, 24 and 48 weeks
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)	NT-proBNP change from baseline at 16, 24, and 48 weeks compared with placebo Part A	Baseline - 16, 24 and 48 weeks
Left Ventricular Global Longitudinal Strain (LV-GLS)	LV-GLS change from baseline at 16 and 24 weeks compared with placebo Part A. Left ventricular global longitudinal strain (LV-GLS) is an echocardiographic measure expressing longitudinal shortening as a percentage. A negative change from baseline indicates a better outcome.	Baseline - 16 and 24 weeks
Left Atrial Volume Index (LAVI)	LAVI change from baseline at 16 and 24 weeks compared with placebo Part A. Left atrial volume index (LAVI) is an echocardiographic measure calculated by dividing LA volume by body surface area. A negative change from baseline indicates a better outcome.	Baseline - 16 and 24 weeks
Left Ventricular Mass Index (LVMI)	LVMI change from baseline at 16 and 24 weeks compared with placebo Part A. Left ventricular mass index (LVMI) is an echocardiographic measure calculated by dividing LVM by body surface area. A negative change from baseline indicates a better outcome.	Baseline - 16 and 24 weeks
Pharmacokinetics (AZD4831 Plasma Exposure)	Plasma concentrations of AZD4831 summarised by timepoint and dose level Part A	Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks, 48 weeks, 52 weeks
High Sensitivity CRP (hsCRP)	hsCRP change from baseline at 16, 24, and 48 weeks compared with placebo Part A	Baseline - 16, 24 and 48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of participants with Adverse Events Part A	Baseline - 52 weeks
Vital Signs	Number of participants with treatment emergent vital sign abnormalities Part A	Baseline - 52 weeks
Clinical Laboratory (Haematology)	Number of participants with outliers for clinical laboratory (chemistry) measurements Part A	Baseline - 52 weeks
Clinical Laboratory (Chemistry)	Number of participants with outliers for clinical laboratory (chemistry) measurements Part A	Baseline - 52 weeks
Electrocardiogram (ECG)	Number of Participants With Abnormal ECG Last On-Study Value Part A	Baseline - 52 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Lund LH, Lam CSP, Pizzato PE, Gabrielsen A, Michaelsson E, Nelander K, Ericsson H, Holden J, Folkvaljon F, Mattsson A, Collen A, Aurell M, Whatling C, Baldus S, Drelich G, Goudev A, Merkely B, Bergh N, Shah SJ. Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction. Eur J Heart Fail. 2023 Sep;25(9):1696-1707. doi: 10.1002/ejhf.2977. Epub 2023 Aug 22.

Helpful Links

• Redacted_CSP
• Redacted CSR synopsis
• D6580C00010_Redacted_SAP

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): March 27, 2024
• Study Completion (Actual): March 27, 2024

Study Registration Dates

• First Submitted: June 18, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Heart failure; Heart failure with preserved ejection fraction; HFpEF
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; AZD4831
• Other Study ID Numbers: D6580C00010; 2020-005844-47 (EudraCT Number)

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. All request 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 shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer 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 de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• 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