An Open-label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 Enzyme Activity Using Probe Substrates
- Registration Number
- NCT02819102
- Lead Sponsor
- BioCryst Pharmaceuticals
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Metabolic Probes and BCX7353 BCX7353 and probes 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.
- Primary Outcome Measures
Name Time Method Cmax of probe substrates plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 Tmax of probe substrates plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 AUClast of probe substrates plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 AUCinf of probe substrates plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 t1/2 of probe substrates plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 Cl of intravenous midazolam plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
- Secondary Outcome Measures
Name Time Method adverse events absolute and change from baseline through study day 11 laboratory analyses absolute and change from baseline through study day 11 Vital signs absolute and change from baseline through study day 11 physical examination findings absolute and change from baseline through study day 11 electrocardiograms absolute and change from baseline through study day 11 C24 for tolbutamide plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 C6 for IV and oral midazolam plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 Probe/metabolite AUC24 ratio plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 Tlag of probe substrates plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 VdF of probe substrates plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 CL/F of oral probe substrates plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11 Vss of intravenous midazolam plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Trial Locations
- Locations (1)
Quotient Clinical Ltd
🇬🇧Ruddington, Nottingham, United Kingdom