Overview

This trial is active, not recruiting.

Condition hereditary angioedema
Treatment bcx7353 and probes
Phase phase 1
Sponsor BioCryst Pharmaceuticals
Start date March 2016
End date July 2016
Trial size 20 participants
Trial identifier NCT02819102, BCX7353-102

Summary

This is an open-label, single sequence study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 enzymes using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification pharmacokinetics study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Day 1: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, and 30 mg dextromethorphan orally. Day 2: a single oral dose of 2 mg midazolam. Days 3 to 9: 350 mg BCX7353 once a day. Day 10: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, 30 mg dextromethorphan and 350 mg BCX7353, orally. Day 11: a single oral dose of 2 mg of midazolam along with 350 mg BCX7353.
bcx7353 and probes

Primary Outcomes

Measure
Cmax of probe substrates
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Tmax of probe substrates
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
AUClast of probe substrates
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
AUCinf of probe substrates
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
t1/2 of probe substrates
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Cl of intravenous midazolam
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Secondary Outcomes

Measure
adverse events
time frame: absolute and change from baseline through study day 11
laboratory analyses
time frame: absolute and change from baseline through study day 11
Vital signs
time frame: absolute and change from baseline through study day 11
physical examination findings
time frame: absolute and change from baseline through study day 11
electrocardiograms
time frame: absolute and change from baseline through study day 11
C24 for tolbutamide
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
C6 for IV and oral midazolam
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Probe/metabolite AUC24 ratio
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Tlag of probe substrates
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
VdF of probe substrates
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
CL/F of oral probe substrates
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Vss of intravenous midazolam
time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Eligibility Criteria

Male or female participants from 18 years up to 55 years old.

Key Inclusion Criteria: - Written informed consent - Body mass index 18 to 32 kg/m2 - Abides by study restrictions - Attends all study visits and agrees to remain in study center for the confinement period - Acceptable birth control measures for male subjects and women of childbearing potential Key Exclusion Criteria: - Clinically significant medical history, current medical or psychiatric condition. This includes a history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, or cardiac disease - Clinically significant ECG finding, vital sign measurement or laboratory/urinalysis abnormality at screening or baseline - Poor or ultra- metabolizers of CYP2C19 or CYP2D6 Use of over the counter or prescription medication within 14 days of dosing and anticipated use through the follow-up visit - Use of medication or consumption of any substance that is known to inhibit or induce metabolic enzymes or transporters within 30 days of dosing - Participation in any other investigational drug study within 90 days of screening - Recent or current history of alcohol or drug abuse - Regular recent use of tobacco or nicotine products - Positive serology for HBV, HCV, or HIV - Pregnant or nursing - Donation or loss of greater than 400 mL of blood within 3 months - Serious adverse reaction or serious hypersensitivity to any drug

Additional Information

Official title A Single Sequence, Open-Label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 3A4, 2C9, 2C19 and 2D6 Enzyme Activity Using Probe Substrates in Healthy Subjects
Principal investigator Litza McKenzie, MBChB
Description This is a single centre, single sequence, open-label, study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 (CYP) 3A4 (midazolam IV and PO, respectively), CYP2C9 (tolbutamide), CYP2C19 (omeprazole) and CYP2D6 (dextromethorphan) enzyme activity using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353. Twenty healthy male and female subjects are planned for dosing. Each subject will receive the following treatments: Day 1: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, and 30 mg dextromethorphan orally. Day 2: a single oral dose of 2 mg midazolam. Days 3 to 9: 350 mg BCX7353 once a day. Day 10: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, 30 mg dextromethorphan and 350 mg BCX7353, orally. Day 11: a single oral dose of 2 mg of midazolam along with 350 mg BCX7353.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by BioCryst Pharmaceuticals.