Effects of PQ912 on the Pharmacokinetics of Midazolam and Omeprazole
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|ClinicalTrials.gov Identifier: NCT02190708|
Recruitment Status : Completed
First Posted : July 15, 2014
Last Update Posted : October 21, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|Healthy Volunteers Pharmacologic Action||Drug: PQ912 Drug: Midazolam Drug: Omeprazole||Phase 1|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||A Phase I, Open Label Study to Assess the Effects of PQ912 on the Pharmacokinetics of Midazolam and Omeprazole in Healthy Male Subjects|
|Study Start Date :||June 2014|
|Actual Primary Completion Date :||June 2014|
|Actual Study Completion Date :||August 2014|
Experimental: PQ912 & Midazolam & Omeprazole
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
from day2 up to day6 twice daily oral dose of PQ912
Other Name: Glutaminyl Cyclase Inhibitor
single oral dose on day1 and day 6
Other Name: benzodiazepine
single oral dose on day1 and day6
Other Name: Proton pump inhibitor
- Effect of PQ912 at steady state on pharmacokinetic profile of Omeprazole and Midazolam [ Time Frame: from day 1 up to day 6 ]Serial blood samples on day 1 and day 6 from predose up to 24 hours postdose
- Safety and tolerability of PQ912 in terms of Adverse Events Assessments when coadministered with Midazolam and Omeprazol [ Time Frame: day-1 up to day 6 and post dose visit ]Safety profile in terms of Adverse Events Assessments
- 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) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02190708
|Covance Clinical Research Unit Ltd|
|Leeds, United Kingdom, LS2 9LH|
|Principal Investigator:||Joseph Chiesa, MD, Dr||Covance|