Healthy Volunteers
Conditions
Keywords
Fixed Sequence Study, Cardiovascular Disease, Drug-drug interaction, Pharmacokinetics, Myeloperoxidase inhibitor
Brief summary
A study to demonstrate pharmacokinetics of AZD4831 when administered alone and in combination with Itraconazole.
Detailed description
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).
Interventions
DRUGAZD4831
Subjects will receive single oral dose only on Day 1 and Day 11.
DRUGItraconazole
Subjects will receive Itraconazole orally on Days 8 followed by dosing from Day 9 to Day 17.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRTinf) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
| Maximum observed plasma (peak) drug concentration (Cmax) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
| Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
| Area under plasma concentration time curve from zero to infinity (AUCinf) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
| Time to reach peak or maximum observed concentration or response following drug administration (tmax) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
| Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
| Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
| Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase (Vz/F) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
| Terminal elimination rate constant (λz) for AZD4831 | Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18 | To assess the effect of Itraconazole on AZD4831 only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events (AE) | From Screening (Day -28 to Day -2) to Follow-up visit (Between Day 25 and Day 32) | To assess safety and tolerability of AZD4831 alone and in combination with Itraconazole. |
Countries
United Kingdom
Outcome results
None listed