Multiple dose AZD5718 effect on Midazolam in HV
Research type
Research Study
Full title
A Fixed Sequence, Open-label Study to Assess the Effect of Multiple Doses of AZD5718 on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Healthy Subjects
IRAS ID
284200
Contact name
Pablo ForteSoto
Contact email
Sponsor organisation
Astra Zeneca AB
Eudract number
2020-002231-30
Duration of Study in the UK
0 years, 2 months, 13 days
Research summary
In vitro studies and a human ADME study showed that the main metabolic elimination pathway of AZD5718 is via CYP3A4 metabolism. In clinical practice, AZD5718 will be co-administered with CYP3A substrates thus, it is important to determine the impact of AZD5718 on the PK of CYP3A4 substrates. The primary objective of this study is to evaluate the effect of AZD5718 on the PK of midazolam, a known sensitive CYP3A4 substrate. The results of this study will support inclusion/exclusion criteria in future clinical studies and if an interaction is observed, form the basis for the classification of the potency of AZD5718 as an inhibitor of CYP3A4.
This is a fixed sequence, open-label study in healthy subjects, performed at a single study center. This study will consist of 3 treatment periods to assess the PK of midazolam when administered alone and in combination with multiple doses of AZD5718.
The study will comprise:
• A screening period of maximum 28 days;
• Three treatment periods during which subjects will be resident from the day before first dosing (Day -1) until at least 24 hours after last dosing (Day 7); discharged on the morning of Day 8, and;
• A final Follow-up Visit within 5 to 7 days after the last administration of investigational medicinal product (IMP).
Subjects will receive midazolam (2 mg) as a single dose on 2 occasions, 6 days apart (Days 1 and 7). The first dose will be prior to dosing with AZD5718 and the second dose after multiple administrations of AZD5718 under fasted conditions, as follows:
• Treatment Period 1: Midazolam only (Day 1)
• Treatment Period 2: AZD5718 only (Days 2-6)
• Treatment Period 3: AZD5718 plus midazolam (Day 7)REC name
London - Brent Research Ethics Committee
REC reference
20/LO/0792
Date of REC Opinion
16 Jul 2020
REC opinion
Further Information Favourable Opinion