Effects of PQ912 on the Pharmacokinetics of Midazolam and Omeprazole
Status:
Completed
Trial end date:
2014-08-01
Target enrollment:
Participant gender:
Summary
Midazolam is a rapid-acting benzodiazepine, with a short half-life (approximately 1.9 hours)
and is primarily metabolised by CYP3A.
Omeprazole is a selective proton pump inhibitor substrate used to reduce gastric acid
secretion. Omeprazole is primarily metabolised by CYP2C19.
Midazolam and omeprazole are both used as probe drugs in clinical pharmacology studies to
evaluate clinical CYP3A and CYP2C19 drug interactions, respectively. Furthermore the EMA and
the FDA guidance on drug interactions recommend the use of these drugs for such evaluations.
The aim of this study is to assess the effect of PQ912 on the PK of midazolam and omeprazole.
In vitro studies have demonstrated that PQ912 inhibits several CYP enzymes, including CYP3A4
and CYP2C19 and at the expected exposure levels in patients, has the potential to inhibit
these enzymes in-vivo. This study is therefore planned to investigate the potential changes
in the PK of midazolam and omeprazole due to the effect of PQ912 at steady-state. In clinical
practice it is likely that co-administration of PQ912 with other drugs that are metabolised
via the CYP3A and/or CYP2C19 enzymes will occur. This study will provide important
information for the requirement of dose adjustments or contraindications in these
circumstances.