Healthy VolunteersPhase 1NCT02190708
Effects of PQ912 on the Pharmacokinetics of Midazolam and Omeprazole
A Phase 1 study testing PQ912, Midazolam and Omeprazole in people with Healthy Volunteers and Pharmacologic Action, run by Vivoryon Therapeutics N.V. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, Pharmacologic Action
- What is being tested?
- PQ912, Midazolam and Omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2014to Aug 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- males
- of any ethnic origin
- between 18 and 55 years of age
- body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive
- body weight between 50 kg and 100 kg inclusive
- must be in good health,
- will have given written informed consent and to abide by the study restrictions
Who cannot join
- history of any clinically significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results, or may limit the subject's ability to participate in the study
- history or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
- active participation in a clinical study or participation in a clinical study investigating a new chemical entity within 3 months or 5 half-lives (whichever is longer prior to first dose)
- clinically significant illness within 4 weeks of the start of the dose administration
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
Read the 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
- Being tested
- PQ912, Midazolam, Omeprazole
- Keywords
- PQ912, Midazolam, Omeprazole, Pharmacokinetics, Drug Interaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PQ912Drug
Also called Glutaminyl Cyclase Inhibitor
from day2 up to day6 twice daily oral dose of PQ912
MidazolamDrug
Also called benzodiazepine
single oral dose on day1 and day 6
OmeprazoleDrug
Also called Proton pump inhibitor
single oral dose on day1 and day6
| Study group | Role | What they receive |
|---|---|---|
| PQ912 & Midazolam & Omeprazole | Experimental | 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 Receives: Drug: PQ912; Drug: Midazolam; Drug: Omeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: from day 1 up to day 6
Secondary outcomes (4)
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
Measured: 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)
Measured: from baseline up to end of study visit (2 weeks after first treatment)
Safety and Tolerability by assessing changes in electrocardiogram (ECG) parameters
Measured: 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)
Measured: from baseline up to end of study visit (2 weeks after first treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2014 (estimated)
- Study startJun 2014
- Primary completionJun 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vivoryon Therapeutics N.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Covance
- Responsible party
- Sponsor
- Investigators
- Joseph Chiesa, MD, Dr, Principal investigator, Covance
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02190708
- Sponsor's protocol ID
- 1002308-8302860
- Other IDs
- 2014-001883-36, 2014
- Status last verified
- Jul 2014
- First submitted
- 4 Jul 2014
- Last updated
- 21 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02190708
- Acronym / sponsor ID
- 1002308-8302860
- Conditions
- Healthy Volunteers, Pharmacologic Action
- Keywords
- PQ912, Midazolam, Omeprazole, Pharmacokinetics, Drug Interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Vivoryon Therapeutics N.V.Industry (pharma, biotech, devices)
- Collaborators
- Covance
- Study start
- Jun 2014
- Primary completion
- Jun 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 15 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PQ912 & Midazolam & Omeprazole | Experimental | Drug: PQ912, Drug: Midazolam, Drug: Omeprazoleday2 - day6 800mg PQ912 twice per day po day1 / day6 2.5 mg Midazolam once per day day1 / day6 20 mg Omeprazole once per day |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- males
- of any ethnic origin
- between 18 and 55 years of age
- body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive
- body weight between 50 kg and 100 kg inclusive
Key exclusion criteria (4 listed)
- history of any clinically significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results, or may limit the subject's ability to participate in the study
- history or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
- active participation in a clinical study or participation in a clinical study investigating a new chemical entity within 3 months or 5 half-lives (whichever is longer prior to first dose)
- clinically significant illness within 4 weeks of the start of the dose administration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PQ912Also: Glutaminyl Cyclase Inhibitorfrom day2 up to day6 twice daily oral dose of PQ912 | Drug | PQ912 & Midazolam & Omeprazole |
| MidazolamAlso: benzodiazepinesingle oral dose on day1 and day 6 | Drug | PQ912 & Midazolam & Omeprazole |
| OmeprazoleAlso: Proton pump inhibitorsingle oral dose on day1 and day6 | Drug | PQ912 & Midazolam & Omeprazole |
Primary outcome
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
4 secondary outcomes
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 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Chiesa, MD, Dr principal investigator
Covance
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PQ912, Midazolam and Omeprazole in people with Healthy Volunteers and Pharmacologic Action, run by Vivoryon Therapeutics N.V. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of PQ912 at steady state on pharmacokinetic profile of Omeprazole and Midazolam (time frame: from day 1 up to day 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2015; AzTrials last refreshed its copy on 8 Nov 2026.