Clinical Trial: An Open-label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 Enzyme Activity Using Probe Substrates

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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.


Sponsor: BioCryst Pharmaceuticals

Current Primary Outcome:

  • 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 ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome: Same as current

Information By: BioCryst Pharmaceuticals

Dates:
Date Received: June 28, 2016
Date Started: March 2016
Date Completion:
Last Updated: January 30, 2017
Last Verified: June 2016