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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
10 mg dose of \[14C\]AZD4831 Oral Solution
Research Site
Ruddington, United Kingdom
The cumulative amount of AZD4831 excreted (CumAe)
Assessment of the total radioactivity by measuring the cumulative amount of AZD4831 excreted (CumAe)
Time frame: Urine and faecal samples collected from pre-dose until 336 hours post-dose
The cumulative amount of AZD4831 excreted and expressed as a percentage of the administered dose (CumFe)
Assessment of the total radioactivity by measuring the cumulative amount of AZD4831 excreted and expressed as a percentage of the administered dose (CumFe)
Time frame: Urine and faecal samples collected from pre-dose until 336 hours post-dose
Assessment of metabolites in plasma by accelerator mass spectrometry (AMS) analysis
Assessment of metabolites and structural identification by AMS analysis
Time frame: Collection of plasma samples from pre-dose until 336 hours post-dose
Assessment of metabolites in urine by AMS analysis
Assessment of metabolites and structural identification by AMS analysis
Time frame: Collection of urine samples from pre-dose until 336 hours post-dose
Assessment of metabolites in faeces by AMS analysis
Assessment of metabolites and structural identification by AMS analysis
Time frame: Collection of faecal samples from pre-dose until 336 hours post-dose
The amount of AZD4831 excreted (Ae)
Assessment of the rates and routes of elimination by measuring the amount excreted (Ae)
Time frame: Collection of urine and faecal samples from pre-dose to 336 hours post-dose.
Amount of AZD4831 excreted and expressed as a percentage of the administered dose (Fe)
Assessment of the rates and routes of elimination by measuring the amount excreted and expressing it as a percentage of the administered dose (Fe)
Time frame: Collection of urine and faecal samples from pre-dose to 336 hours post-dose
The cumulative amount of AZD4831 excreted (CumAe)
Assessment of the rates and routes of elimination by measuring the cumulative amount excreted (CumAe)
Time frame: Collection of urine and faecal samples from pre-dose to 336 hours post-dose
The cumulative amount of AZD4831 excreted and expressed as a percentage of the administered dose (CumFe)
Assessment of the rates and routes of elimination by measuring the cumulative amount excreted and expressed as a percentage of the administered dose (CumFe)
Time frame: Collection of urine and faecal samples from pre-dose to 336 hours post-dose
Time to maximum concentration (tmax) for AZD4831 and total radioactivity
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring the time to maximum concentration (tmax)
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
Maximum plasma concentration (cmax) for AZD4831 and total radioactivity
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring the maximum concentration (cmax)
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
Area under the concentration time curve from time zero to the time of the last measureable concentration (AUC0-t) for AZD4831 and total radioactivity
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring the concentration time curve from time zero to the last measureable concentration (AUC0-t)
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
Area under the concentration time curve from time zero to the last quantifiable concentration (AUC0-inf) for AZD4831 and total radioactivity
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring the concentration time curve from time zero extrapolated to infinity (AUC0-inf)
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
Area under the concentration time curve from time of the last measureable concentration to infinity as a percentage of the area under the curve extrapolated to infinity (AUC%extrap)
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring the concentration time curve from time of the last measureable concentration to infinity as a percentage of the area under the curve extrapolated to infinity (AUC%extrap)
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
Apparent terminal elimination half-life (t1/2) for AZD4831 and total radioactivity
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring the terminal elimination half-life (t1/2)
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
First order rate constant associated with the terminal (log-linear) portion of the curve for AZD4831 and total radioactivity
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring the first order rate constant associated with the terminal (log-linear) portion of the curve
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
Total body clearance (CL/F) of AZD4831 and total radioactivity
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring total body clearance (CL/F)
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
Apparent volume of distribution (Vz/F) of AZD4831 and total radioactivity
Assessment of pharmacokinetics of AZD4831 and total radioactivity by measuring the apparent volume of distribution (Vz/F)
Time frame: Collection of plasma samples from pre-dose to 336 hours post-dose
Renal clearance (CLR) of AZD4831 in urine
Assessment of pharmacokinetics of AZD4831 by measuring renal clearance (CLR)
Time frame: Collection of urine samples from pre-dose to 36 hours post-dose
Evaluation of whole blood to plasma concentration ratios for total radioactivity
Assessment of total radioactivity in whole blood and plasma
Time frame: Collection of blood samples until 336 hours post-dose
Number of adverse events (AE) experienced by subjects
Safety and tolerability assessed through the incidence of AEs
Time frame: AEs recorded from the time of informed consent until discharge from the study (336 hours post-dose)
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