Phase 1 Study - Multiple dose AZD4831 effect on PK of oral Midazolam

• Research type

  Research Study

• Full 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

• IRAS ID

  300827

• Contact name

  David Steel

• Contact email

  David.Steel@parexel.com

• Sponsor organisation

  AstraZeneca AB

• Eudract number

  2021-002793-12

• Duration of Study in the UK

  0 years, 1 months, 23 days

• Research summary

  This is a fixed sequence, open-label study in healthy subjects, performed at a single study center in up to 14 healthy male and female volunteers.

  The main purpose of the clinical trial is to investigate whether AZD4831 affects how midazolam is taken up, metabolised (chemically broken down), distributed through the body, and cleared from the body (referred to as pharmacokinetics or PK). Midazolam, a registered drug, like AZD4831, is broken down by the cytochrome CYP450 3A4 specific drug-degrading enzyme.

  The clinical trial will also assess how safe AZD4831 is and how well it is tolerated when given alone and in combination with midazolam.

  The study will comprise:
  • A Screening Period of maximum 28 days;
  • Two treatment periods during which volunteers will be resident from the day before first dosing (Day 1) until Day 3, as well as from Day 10 to 12. On Days 4 to 9, outpatient dosing with AZD4831 will be performed if feasible.

  Subjects will receive 2 mg midazolam as a single dose on 2 occasions, 10 days apart (Days 1 and 11). The first dose will be prior to dosing with AZD4831 and the second dose after multiple administrations of AZD4831 under fasted conditions, as follows:

  o Treatment Period 1: 2 mg midazolam (oral solution) only (Day 1)
  o Treatment Period 2: AZD4831 (tablet) only (Days 2 to 10) and AZD4831 plus 2 mg midazolam (Day 11)

  • A final Follow-up Visit on Day 20 (± 1 day).

  This is not a first-in-human study as the study drug has been given to humans before in clinical studies. AZD4831 is being developed for the treatment of cardiovascular disease.

• REC name

  South Central - Berkshire B Research Ethics Committee

• REC reference

  21/SC/0185

• Date of REC Opinion

  15 Jul 2021

• REC opinion

  Favourable Opinion