Study to Assess the Effect of AZD4831 on the Pharmacokinetics (Drug Behavior in the Body) of Midazolam

Healthy Volunteers Clinical Trial

Official title:

A Fixed Sequence, Open-label Study to Assess the Effect of Multiple Doses of AZD4831 on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05052710
• Other study ID #: D6580C00012
• Status: Completed
• Phase: Phase 1
• Start date: October 5, 2021
• Est. completion date: November 29, 2021

Study information

• Verified date: December 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is an open-label, fixed-sequence, cross-over study conducted at a single Clinical Unit to assess the pharmacokinetics (PK) of midazolam in healthy male and female (non-childbearing potential) subjects when administered alone and in combination with AZD4831 after multiple doses (once daily) of AZD4831 for 10 consecutive days.

Description:

The study will consist of 2 treatment periods and will comprise:

• A Screening period of maximum 28 days;

• Treatment Period 1 and Treatment Period 2:

Treatment Period 1: Midazolam only (Day 1). Treatment Period 2: AZD4831 only (Days 2 to 10, once daily dosing) and AZD4831 plus midazolam (Day 11).

• A final Follow-up Visit after the last administration of investigational medicinal product (IMP) (Day 20 [± 1 day]).

Each subject will be involved in the study for approximately 7 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: November 29, 2021
• Est. primary completion date: November 29, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male and/or female subjects 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, confirmed at Screening.

• Have a body mass index between 18.5 and 30 kg/m^2 (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.

• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.

• A positive Corona Virus Disease 2019 test at Screening or admission to the Clinical Unit on Day -1.

• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results.

• Any clinically significant abnormal findings in vital signs.

• clinically significant abnormalities on 12-lead electrocardiogram.

• Any positive result at the Screening Visit for Hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody.

• Known or suspected history of drug abuse in the last 2 years.

• Current smokers or those who have smoked or used nicotine products within the 3 months prior to the Screening Visit.

• Known or suspected history of alcohol or drug abuse.

• Use of any prescribed or non-prescribed medication.

• Subjects with acute pulmonary insufficiency, marked neuromuscular respiratory weakness, obsessional states, phobic states, sleep apnoea syndrome, or unstable myasthenia gravis.

• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigatoror history of hypersensitivity to drugs with a similar chemical structure or class to AZD4831 or midazolam.

• History or ongoing allergy/hypersensitivity to drugs(including but not limited to rash, angioedema, acute urticaria).

• 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 oral doses once daily from Days 2-11.
• Midazolam
Subjects will receive oral single doses on Day 1 and Day 11.

Locations

Country	Name	City	State
United Kingdom	Research Site	Harrow

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam	Effect of AZD4831 on AUCinf of Midazolam will be assessed.	Days 1, 2, 11, and 12
Primary	Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Midazolam	Effect of AZD4831 on AUClast of Midazolam will be assessed.	Days 1, 2, 11, and 12
Primary	Maximum observed plasma (peak) drug concentration (Cmax) of Midazolam	Effect of AZD4831 on Cmax of Midazolam will be assessed.	Days 1, 2, 11, and 12
Secondary	Time to reach peak or maximum observed concentration or response following drug administration (tmax) of Midazolam and AZD4831	tmax of Midazolam and AZD4831 will be assessed.	Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Secondary	Half life associated with terminal slope (?z) of a semi logarithmic concentration timecurve (t½?z) of Midazolam and AZD4831	t½?z of Midazolam and AZD4831 will be assessed.	Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Secondary	Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Midazolam and AZD4831	CL/F of Midazolam and AZD4831 will be assessed.	Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Secondary	Apparent volume of distribution based on terminal phase (Vz/F) of Midazolam	Vz/F of Midazolam will be assessed.	Days 1, 2, 11, and 12
Secondary	Area under the plasma concentration-curve across the dosing interval (AUCtau) of AZD4831	AUCtau of AZD4831 will be assessed.	Days 2-12
Secondary	Cmax of AZD4831	Cmax of AZD4831 will be assessed.	Days 2-12
Secondary	Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831	Pre-dose plasma concentration of AZD4831 will be assessed.	Days 3-10
Secondary	Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831	Plasma concentration of AZD4831 will be assessed.	Day 11
Secondary	Number of patients with adverse events (AE) and serious AEs (SAE)	Safety and tolerability of AZD4831 alone and in combination with midazolam will be assessed.	From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20)