A Phase 1 interventional study of PQ912 and Midazolam in Healthy Volunteers and Pharmacologic Action, sponsored by Vivoryon Therapeutics N.V.. Completed at 1 site in United Kingdom. Open to male participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2015-10-21.
Sponsored by Vivoryon Therapeutics N.V. · Phase 1, Interventional, and Basic science
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.
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.
Vivoryon Therapeutics N.V. is the lead sponsor of 4 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
day2 - day6 800mg PQ912 twice per day po day1 / day6 2.5 mg Midazolam once per day day1 / day6 20 mg Omeprazole once per day
Drug: PQ912 · Drug: Midazolam · Drug: Omeprazole
from day2 up to day6 twice daily oral dose of PQ912
Also known as: Glutaminyl Cyclase Inhibitor
single oral dose on day1 and day 6
Also known as: benzodiazepine
single oral dose on day1 and day6
Also known as: Proton pump inhibitor
Effect of PQ912 at steady state on pharmacokinetic profile of Omeprazole and Midazolam
Serial blood samples on day 1 and day 6 from predose up to 24 hours postdose
Time frame: from day 1 up to day 6
Safety and tolerability of PQ912 in terms of Adverse Events Assessments when coadministered with Midazolam and Omeprazol
Safety profile in terms of Adverse Events Assessments
Time frame: day-1 up to day 6 and post dose visit
Safety and tolerability in terms of vital signs (blood pressure, pulse rate, respiration rate, Body temperature)
Time frame: from baseline up to end of study visit (2 weeks after first treatment)
Safety and Tolerability by assessing changes in electrocardiogram (ECG) parameters
Time frame: from baseline up to end of study visit (2 weeks after first treatment)
Safety and tolerability in terms of lab tests assessment (hematology, Serum biochemistry, serology, urinalysis)
Time frame: from baseline up to end of study visit (2 weeks after first treatment)
This study is completed, as verified in Jul 2014. You cannot join it, but the record below documents what was studied.
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Vivoryon Therapeutics N.V.