NCT04407091

A Study to Assess the Mass Balance Recovery, Pharmacokinetics, Metabolite Profile and Metabolite Identification of [14C]AZD4831

Completed Phase 1 Last updated 25 August 2020

What this trial tests

Phase 1 trial testing 14C]AZD4831 Oral Solution in Cardiovascular Disease in 8 participants. Completed in 6 August 2020.

Timeline

30 June 2020

Primary endpoint
6 August 2020

6 August 2020

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	8
Start date	30 June 2020
Primary completion	6 August 2020
Estimated completion	6 August 2020
Sites	1 location across United Kingdom

Drugs / interventions tested

• 14C]AZD4831 Oral Solution — full drug profile →

Conditions studied

• Cardiovascular Disease — all drugs for Cardiovascular Disease →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 65, male only, with Cardiovascular Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The Sponsor is developing the test medicine, AZD4831, for the potential treatment of cardiovascular disease (CVD). CVD is a general term to describe a range of conditions that affect the heart and blood vessels, examples of CVD include angina (chest pain caused by restricted blood flow to heart muscle) and heart failure (where the heart is unable to pump blood around the body properly). AZD4831 is an inhibitor of a protein that has a role in the formation of fatty deposits in arteries (blood vessels that take blood to the body). It is hoped that by inhibiting this action, AZD4831 will help with the management of CVD.

The study involves radiolabelling (labelling the molecule with radioactive 14C) which is used to locate the molecule within the body. The study will try to assess how much radioactivity can be recovered from the urine and faeces (mass balance recovery) after a single oral dose of \[14C\]AZD4831. It will also look to identify the breakdown products (metabolites) of the parent drug. It will additionally determine the rate and route of elimination of \[14C\]AZD4831, along with the level of test medicine in the blood. The safety and tolerability of the test medicine will be assessed. The dose of radiation administered is very low, therefore the risk associated with this is very small.

The study will consist of a single study period involving up to six healthy male volunteers. Up to six male volunteers will receive a dose of 10 mg of the radiolabelled test medicine as an oral solution. Blood, urine and faecal samples will be collected from volunteers whilst they are resident in the clinical unit for up to 336 hours post-dose (Day 15). A follow-up visit will take place seven to ten days after discharge for safety assessments.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction.
   Inghardt T, Antonsson T, Ericsson C, Hovdal D, et al · · 2022 · cited 26× · PMID 36005476 · DOI 10.1021/acs.jmedchem.1c02141
2. Biotransformation of the Novel Myeloperoxidase Inhibitor AZD4831 in Preclinical Species and Humans.
   Jurva U, Weidolf L, Sandinge AS, Leandersson C, et al · · 2023 · cited 7× · PMID 36653117 · DOI 10.1124/dmd.122.001099