A Study to Assess the Pharmacokinetics of AZD4831 When Administered Alone and in Combination With Itraconazole

NCT05236543 | Completed Phase 1

• 2 other identifiers: D6580C000132021-005727-21
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

A study to demonstrate pharmacokinetics of AZD4831 when administered alone and in combination with Itraconazole.

Conditions

Healthy Volunteers

Keywords

Fixed Sequence Study; Cardiovascular Disease; Drug-drug interaction; Pharmacokinetics; Myeloperoxidase inhibitor

Outcome Measures

Primary Outcomes (9)

• Maximum observed plasma (peak) drug concentration (Cmax) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

• Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

• Area under plasma concentration time curve from zero to infinity (AUCinf) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

• Time to reach peak or maximum observed concentration or response following drug administration (tmax) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

• Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

• Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

• Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase (Vz/F) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

• Terminal elimination rate constant (λz) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

• Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRTinf) for AZD4831

  To assess the effect of Itraconazole on AZD4831 only.

  Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18

Secondary Outcomes (1)

• Number of subjects with adverse events (AE)

  From Screening (Day -28 to Day -2) to Follow-up visit (Between Day 25 and Day 32)

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Subjects will receive AZD4831 on Day 1; Itraconazole only on Days 8 through 10 , and AZD4831 and Itraconazole on Day 11 oral dosing of Itraconazole only on Days 12 through 17.

Drug: AZD4831; Drug: Itraconazole

Interventions

AZD4831 DRUG

Subjects will receive single oral dose only on Day 1 and Day 11.

Treatment Arm

Itraconazole DRUG

Subjects will receive Itraconazole orally on Days 8 followed by dosing from Day 9 to Day 17.

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male and female (non-childbearing potential) subjects aged 18 to 55 years (inclusive) at the time of signing informed consent, with suitable veins for cannulation or repeated venepuncture.
• Males must be willing to use appropriate contraception methods.
• Females must not be lactating and must be of non-childbearing potential.
• Have a .BMI between 18.5 and 30.0 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive) at Screening.

You may not qualify if:

• History of any clinically significant disease or disorder, including hyperthyroidism, uncontrolled hypothyroidism or any clinically significant thyroid disease.
• History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational medicinal product (IMP).
• A positive COVID-19 test at the Screening Visit or admission to the Clinical Unit.
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis, vital signs, and 12-lead ECG.
• Any positive result at the Screening Visit for serum Hepatitis B surface antigen (HBsAg), HCV, and Human immunodeficiency virus (HIV) antibody.
• Known or suspected Gilbert's syndrome.
• Known or suspected history of drug abuse in the last 2 years, as judged by the Investigator.
• Has received another new chemical or biological entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study or final follow up visit within 1 month of first administration of IMP in this study.
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to the Screening Visit.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4831 or itraconazole.
• Current smokers or those who have smoked or used nicotine products (including e cigarettes).
• Excessive intake of caffeine-containing drinks or foods.
• Known or suspected history of alcohol or excessive intake of alcohol.
• Positive screen for drugs of abuse or cotinine at screening.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

AZD4831; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

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: February 2, 2022
• First Posted: February 11, 2022
• Study Start: February 18, 2022
• Primary Completion: August 12, 2022
• Study Completion: August 12, 2022
• Last Updated: August 23, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• 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.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified 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.

Locations

GB (1)