NCT02190708

Effects of PQ912 on the Pharmacokinetics of Midazolam and Omeprazole

A Phase I, Open Label Study to Assess the Effects of PQ912 on the Pharmacokinetics of Midazolam and Omeprazole in Healthy Male Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Vivoryon Therapeutics N.V. · Industry
• Sex: Male
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

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.

Detailed description

This will be an open-label, crossover, fixed sequence study in healthy male subjects. Thirty six (36) subjects will participate in the study and will be enrolled as two groups of 18 (Groups 1 and 2). If the PK data from Group 1 demonstrate a clinically important inhibition of the CYP3A4 and/or CYP2C19 enzymes then the second optional group (Group 2) might be studied at a lower dose level of PQ912 . Each subject will participate in one treatment period, residing at the CRU from Day -1 (the day before dosing) to Day 7 (until after the last PK sampling occasion). All subjects will return for a post study visit 5 to 7 days after their final dose. Dose Regimen: Each subject will receive single oral doses of midazolam and omeprazole on the morning of Day 1. On the morning of Day 2, all subjects will commence the multiple dose regimen for PQ912, which will continue for 5 days in total. Subjects in Group 1 and (if it necessary) in Group 2 will receive PQ912 twice daily (bid) on Days 2 to 6 inclusive and subjects in Group 2 will receive PQ912 bid on Days 2 to 6 inclusive. On the morning of Day 6 subjects will be given single oral doses of midazolam and omeprazole co-administered with PQ912.

Conditions

• Healthy Volunteers
• Pharmacologic Action

Interventions

Type	Name	Description
DRUG	PQ912	from day2 up to day6 twice daily oral dose of PQ912
DRUG	Midazolam	single oral dose on day1 and day 6
DRUG	Omeprazole	single oral dose on day1 and day6

Timeline

• Start date: 2014-06-01
• Primary completion: 2014-06-01
• Completion: 2014-08-01
• First posted: 2014-07-15
• Last updated: 2015-10-21

Locations

1 site across 1 country: United Kingdom