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

NCT04407091 | Completed Phase 1

• 1 other identifier: D6580C00007
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiovascular Disease

Keywords

Heart Failure with preserved Ejection Fraction (HFpEF)

Outcome Measures

Primary Outcomes (5)

• The cumulative amount of AZD4831 excreted (CumAe)

  Assessment of the total radioactivity by measuring the cumulative amount of AZD4831 excreted (CumAe)

  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)

  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

  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

  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

  Collection of faecal samples from pre-dose until 336 hours post-dose

Secondary Outcomes (16)

• The amount of AZD4831 excreted (Ae)

  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)

  Collection of urine and faecal samples from pre-dose to 336 hours post-dose

• The cumulative amount of AZD4831 excreted (CumAe)

  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)

  Collection of urine and faecal samples from pre-dose to 336 hours post-dose

• Time to maximum concentration (tmax) for AZD4831 and total radioactivity

  Collection of plasma samples from pre-dose to 336 hours post-dose

Other Outcomes (3)

• Identification of the chemical structure of major metabolite(s) in plasma

  Plasma samples collected until 336 hours post-dose

• Identification of the chemical structure of major metabolite(s) in urine

  Urine samples collected until 336 hours post-dose

• Identification of the chemical structure of major metabolite(s) in faeces

  Faeces samples collected until 336 hours post-dose

Study Arms (1)

[14C]AZD4831 Oral Solution

EXPERIMENTAL

One 10 mg dose of \[14C\]AZD4831 Oral Solution

Drug: 14C]AZD4831 Oral Solution

Interventions

14C]AZD4831 Oral Solution DRUG

10 mg dose of \[14C\]AZD4831 Oral Solution

Also known as: [14C]AZD4831

[14C]AZD4831 Oral Solution

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Healthy male subjects
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated written informed consent prior to any study specific procedures.
• Healthy male subjects aged 18 to 65 years inclusive at the time of signing informed consent with suitable veins for cannulation or repeated venepuncture.
• Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening.
• Must be willing and able to communicate and participate in the whole study.
• Must have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day).
• Must agree to adhere to the contraception requirements

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• History of presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Subjects with uncontrolled or clinically significant thyroid disease as judged by the investigator.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of the IMP.
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator. Subjects with known Gilbert's Syndrome or persistently elevated unconjugated bilirubin are not allowed. Subjects with haemoglobin \< lower limit of normal (LLN), white blood cell or neutrophil count \<LLN (subjects of African origin with neutrophil count \<1.8 × 109/L).
• Any clinically significant abnormal findings in vital signs, as judged by the investigator. Subjects with history of orthostatic hypotension or those who are noted to have a fall in systolic blood pressure \>/=20 mmHg or diastolic blood pressure \>/=10 mmHg and/or elevation in heart rate of more than 30 bpm or heart rate on standing \>120/min when checked 2 min after change of posture at screening or at pre-dose.
• Any clinically significant abnormalities on 12-lead ECG as judged by the investigator.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibody, (HCV Ab) and human immunodeficiency virus (HIV) antibody.
• Known or suspected history of drug abuse within the past 2 years, as judged by the investigator.
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
• Subjects with ongoing skin disorder or history of significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4831 or the formulation excipients. Hay fever is allowed unless it is active.
• Current smokers or those who have smoked or used nicotine products within the previous 3 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.
• Current users of e-cigarettes and those who have used e-cigarettes within the last 3 months.
• Positive screen for drugs of abuse at screening or admission to the clinical unit or positive screen for alcohol at screening or admission to the clinical unit.
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol \>21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type)

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Study Officials

• Somasekhara Menakuru, MBBS, MS, MRCS, DPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2020
• First Posted: May 29, 2020
• Study Start: June 30, 2020
• Primary Completion: August 6, 2020
• Study Completion: August 6, 2020
• Last Updated: August 25, 2020

Record last verified: 2020-08

Locations

GB (1)