Effects of PQ912 on the Pharmacokinetics of Midazolam and Omeprazole

NCT02190708 | Completed Phase 1

• 2 other identifiers: 1002308-83028602014-001883-36
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers; Pharmacologic Action

Keywords

PQ912; Midazolam; Omeprazole; Pharmacokinetics; Drug Interaction

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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)

  from baseline up to end of study visit (2 weeks after first treatment)

• Safety and Tolerability by assessing changes in electrocardiogram (ECG) parameters

  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)

  from baseline up to end of study visit (2 weeks after first treatment)

Study Arms (1)

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

Drug: PQ912; Drug: Midazolam; Drug: Omeprazole

Interventions

PQ912 DRUG

from day2 up to day6 twice daily oral dose of PQ912

Also known as: Glutaminyl Cyclase Inhibitor

PQ912 & Midazolam & Omeprazole

Midazolam DRUG

single oral dose on day1 and day 6

Also known as: benzodiazepine

PQ912 & Midazolam & Omeprazole

Omeprazole DRUG

single oral dose on day1 and day6

Also known as: Proton pump inhibitor

PQ912 & Midazolam & Omeprazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vivoryon Therapeutics N.V.: lead
• Covance: collaborator

Study Sites (1)

Covance Clinical Research Unit Ltd

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Interventions

Midazolam; Benzodiazepines; Omeprazole; Proton Pump Inhibitors

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Joseph Chiesa, MD, Dr

  Covance

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2014
• First Posted: July 15, 2014
• Study Start: June 1, 2014
• Primary Completion: June 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 21, 2015

Record last verified: 2014-07

Locations

GB (1)