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

NCT05052710 | Completed Phase 1

• 1 other identifier: D6580C00012
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

Cardiovascular Disease; Drug-drug interaction; Pharmacokinetics; Myeloperoxidase inhibitor; Fixed-sequence

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (9)

• Time to reach peak or maximum observed concentration or response following drug administration (tmax) of Midazolam and AZD4831

  Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12

• Half life associated with terminal slope (λz) of a semi logarithmic concentration timecurve (t½λz) of Midazolam and AZD4831

  Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12

• Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Midazolam and AZD4831

  Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12

• Apparent volume of distribution based on terminal phase (Vz/F) of Midazolam

  Days 1, 2, 11, and 12

• Area under the plasma concentration-curve across the dosing interval (AUCtau) of AZD4831

  Days 2-12

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Subjects will receive midazolam on Day 1 and AZD4831 once daily from Days 2 to 10, and AZD4831 plus midazolam on Day 11.

Drug: AZD4831; Drug: Midazolam

Interventions

AZD4831 DRUG

Subjects will receive oral doses once daily from Days 2-11.

Treatment Arm

Midazolam DRUG

Subjects will receive oral single doses on Day 1 and Day 11.

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

AZD4831; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: September 22, 2021
• Study Start: October 5, 2021
• Primary Completion: November 29, 2021
• Study Completion: November 29, 2021
• Last Updated: December 13, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

GB (1)