Myeloperoxidase (MPO) Inhibitor A_Zeneca for Heart Failure With Preserved Ejection Fraction (HFpEF)

NCT03611153 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17-002907UL1TR000135
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Researchers are studying the effect of a single dose of oral myeloperoxidase on heart failure versus placebo.

Conditions

Heart Failure

Keywords

Heart Failure; Ejection Fraction; Preserved; Myeloperoxidase Inhibitor; Exercise

Outcome Measures

Primary Outcomes (2)

• Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP)

  Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.

  Baseline, approximately 30 minutes after study drug administration

• Exercise Pulmonary Capillary Wedge Pressure (PCWP)

  Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.

  Baseline

Secondary Outcomes (5)

• Change in Resting Pulmonary Capillary Wedge Pressure (PCWP)

  Baseline, approximately 30 minutes after study drug administration

• Change in Exercise Central Pressures

  Baseline, approximately 30 minutes after study drug administration

• Change in Resting Central Pressures

  Baseline, approximately 30 minutes after study drug administration

• Change in Exercise Transmyocardial Lactate Ratio

  Baseline, approximately 30 minutes after drug administration

• Change in Resting Transmyocardial Lactate Ratio

  Baseline, approximately 30 minutes after drug administration

Study Arms (2)

AZD4831 Oral myeloperoxidase inhibitor

EXPERIMENTAL

Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization.

Drug: AZD4831 Oral Myeloperoxidase Inhibitor

Placebo

PLACEBO COMPARATOR

Patient may take 30 mg of placebo oral capsule following baseline right heart catheterization.

Drug: Placebo oral capsule

Interventions

AZD4831 Oral Myeloperoxidase Inhibitor DRUG

A single administration dose of 30 mg oral MPO inhibitor given orally following baseline, resting and exercise testing in patients during right heart catheterization.

Also known as: Oral MPO inhibitor AZD4831

AZD4831 Oral myeloperoxidase inhibitor

Placebo oral capsule DRUG

A single administration dose of 30 mg placebo given orally following baseline, resting and exercise testing in patients during right heart catheterization.

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females of non-childbearing potential
• Age ≥ 30 years
• Symptoms of dyspnea (II-IV) at the time of screening
• Ejection Fraction (EF) ≥ 50% as determined on imaging study within 12 months of enrollment
• Catheterization documented elevated filling pressures at rest (PCWP ≥15) or with exercise (PCWP ≥25)

You may not qualify if:

• Use of nitrates, phosphodiesterase 5 inhibitors or other NO-providing therapy in the past 24 hours of screening
• Significant valvular disease (\>moderate left-sided regurgitation, \>mild stenosis)
• Requirement of intravenous heparin at the start of case
• Severe pulmonary parenchymal disease
• Acute coronary syndrome or coronary disease requiring revascularization in the judgement of investigators
• Resting systolic blood pressure \< 100 mmHg
• Constrictive pericarditis
• Infiltrative, restrictive, or hypertrophic obstructive cardiomyopathies
• Previous anaphylaxis to any drug
• Pregnancy or breastfeeding mothers
• High Output heart failure
• Active thyroid disease
• Treatment with a new chemical entity (defined as a compound which has not been approved for marketing) within the preceding 3 months
• Patients with any prior allergy to propylthiouracil

Sponsors & Collaborators

• Mayo Clinic: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Heart Failure; Motor Activity

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Behavior

Results Point of Contact

• Title: Dr. Barry A. Borlaug
• Organization: Mayo Clinic

borlaug.barry@mayo.edu

507-255-2200

Study Officials

• Barry A Borlaug, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Only research pharmacy staff will be aware of randomization scheme and all study personnel and subjects will remain blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Single Administration of study drug

Study Record Dates

• First Submitted: July 26, 2018
• First Posted: August 2, 2018
• Study Start: July 1, 2018
• Primary Completion: February 11, 2022
• Study Completion: February 24, 2022
• Last Updated: January 8, 2025
• Results First Posted: January 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)