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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05236543
• Other study ID #: D6580C00013
• Secondary ID: 2021-005727-21
• Status: Completed
• Phase: Phase 1
• Start date: February 18, 2022
• Est. completion date: August 12, 2022

Study information

• Verified date: August 2022
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 12, 2022
• Est. primary completion date: August 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• AZD4831
Subjects will receive single oral dose only on Day 1 and Day 11.
• Itraconazole
Subjects will receive Itraconazole orally on Days 8 followed by dosing from Day 9 to Day 17.

Locations

Country	Name	City	State
United Kingdom	Research Site	Harrow

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Half life associated with terminal slope (?z) of a semi logarithmic concentration time curve (t½?z) 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
Primary	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
Primary	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
Primary	Terminal elimination rate constant (?z) 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
Primary	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	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)