Clinical trial NCT05236543: A Study to Assess the Pharmacokinetics of AZD4831 When Administered Alone and in Combination With Itraconazole
Official title: An Open-label, Fixed Sequence Study in Healthy Subjects to Assess the Pharmacokinetics of AZD4831 When Administered Alone and in Combination With Itraconazole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Fixed Sequence Study
Cardiovascular Disease
Drug-drug interaction
Pharmacokinetics
Myeloperoxidase inhibitor
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2022-02-11
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum observed plasma (peak) drug concentration (Cmax) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
measure: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
measure: Area under plasma concentration time curve from zero to infinity (AUCinf) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
measure: Time to reach peak or maximum observed concentration or response following drug administration (tmax) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
measure: Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
measure: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
measure: Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase (Vz/F) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
measure: Terminal elimination rate constant (λz) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
measure: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRTinf) for AZD4831
timeFrame: Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18
Secondary outcomes:
measure: Number of subjects with adverse events (AE)
timeFrame: From Screening (Day -28 to Day -2) to Follow-up visit (Between Day 25 and Day 32)
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
References: