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

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

Detailed Description
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This will be a an open-label, 3-period fixed sequence study to be conducted at a single study centre. The treatment starts with AZD4831 (Treatment Period 1), followed by Itraconazole administration for 3 days (Treatment Period 2) and finally a combination of AZD4831+Itraconazole administration (Treatment Period 3). The study will comprise of: A Screening Period of approximately 28 days. Three Treatment Periods: Treatment Period 1 (Day -1 through pre-dose Day 8): Single oral dose of AZD4831 only on Day 1, Treatment Period 2 (Day 8 through pre-dose Day 11): Oral dose of Itraconazole only on Days 8 through 10, Treatment Period 3 (Day 11 through Day 18, after the last PK sample is collected): AZD4831 and Itraconazole on Day 11 and oral dosing of Itraconazole only on Days 12 through 17. A final Follow-up Visit after the last PK sample (Day 25 to Day 32). Each subject will be involved in the study for approximately 9 weeks (including the 28 day Screening Period).

Official Title
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An Open-label, Fixed Sequence Study in Healthy Subjects to Assess the Pharmacokinetics of AZD4831 When Administered Alone and in Combination With Itraconazole

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: AZD4831
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP. Use of any prescribed or non prescribed medication including COVID-19 vaccines, antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life. Subjects who have previously received AZD4831. Subjects who are lactose intolerant or have other specific dietary restrictions that cannot be accommodated by the Clinical Unit. Subjects who, in the opinion of the Investigator, have any clinically significant skin condition.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>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<br>* Subjects will receive single oral dose only on Day 1 and Day 11.<br>Drug: Itraconazole<br>* Subjects will receive Itraconazole orally on Days 8 followed by dosing from Day 9 to Day 17.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events (AE) | To assess safety and tolerability of AZD4831 alone and in combination with Itraconazole. | From Screening (Day -28 to Day -2) to Follow-up visit (Between Day 25 and Day 32) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fixed Sequence Study, Cardiovascular Disease, Drug-drug interaction, Pharmacokinetics, Myeloperoxidase inhibitor