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Completed

NCT Number: NCT05052710

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

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.

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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site

Harrow, HA1 3UJ, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

AZD4831

Drug

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

midazolam

Drug

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

Primary outcomes

  1. Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam

    Time frame: Days 1, 2, 11, and 12

    Effect of AZD4831 on AUCinf of Midazolam will be assessed.

  2. Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Midazolam

    Time frame: Days 1, 2, 11, and 12

    Effect of AZD4831 on AUClast of Midazolam will be assessed.

  3. Maximum observed plasma (peak) drug concentration (Cmax) of Midazolam

    Time frame: Days 1, 2, 11, and 12

    Effect of AZD4831 on Cmax of Midazolam will be assessed.

Secondary outcomes

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

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

    tmax of Midazolam and AZD4831 will be assessed.

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

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

    t½λz of Midazolam and AZD4831 will be assessed.

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

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

    CL/F of Midazolam and AZD4831 will be assessed.

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

    Time frame: Days 1, 2, 11, and 12

    Vz/F of Midazolam will be assessed.

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

    Time frame: Days 2-12

    AUCtau of AZD4831 will be assessed.

  6. Cmax of AZD4831

    Time frame: Days 2-12

    Cmax of AZD4831 will be assessed.

  7. Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831

    Time frame: Days 3-10

    Pre-dose plasma concentration of AZD4831 will be assessed.

  8. Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831

    Time frame: Day 11

    Plasma concentration of AZD4831 will be assessed.

  9. Number of patients with adverse events (AE) and serious AEs (SAE)

    Time frame: From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20)

    Safety and tolerability of AZD4831 alone and in combination with midazolam will be assessed.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2021
Study completion
2021
First posted
Sep 22, 2021
Registry last updated
Dec 13, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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