Clinical Trial: First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BCX7353 in Healthy Western and Japanese Volunteers

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

Official Title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of BCX7353 in Heal

Brief Summary: This is a 3-part Phase 1 dose-ranging study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single (Part 1) and multiple (Part 2) ascending doses of BCX7353 in healthy subjects, and single and multiple doses of BCX7353 in healthy Japanese subjects. Pharmacokinetics is an analysis of how the body handles the study drug BCX7353 and pharmacodynamics is an analysis of the activity the study drug BCX7353 may have in the body.

Detailed Summary:

Up to 6 ascending, single dose cohorts are planned to be dosed in a sequential manner in Part 1 of the study. Eight subjects will be treated with a single dose of study drug per dose cohort (6 subjects per cohort will receive BCX7353 and 2 subjects per cohort will receive matching placebo). Escalation to the next higher dose level will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and PI.

Up to 4 ascending, multiple dose cohorts will be enrolled in a sequential manner in Part 2 of the study. Twelve subjects will be treated with study drug per dose cohort (10 subjects will receive BCX7353 and 2 subjects will receive placebo per cohort). The planned doses, dosing regimens, and duration of dosing (7 or 14 days) for each of the Part 2 cohorts will be determined based upon safety and pharmacokinetic data collected during the study. Escalation to the next higher dose level in Part 2 will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and clinical site study physician.

In Part 3 of the study, the safety, tolerability, PK, and PD of single and multiple doses of oral BCX7353 versus placebo in healthy subjects of Japanese origin will be evaluated. In the single dose cohort, 16 Japanese subjects will be randomized into a single cohort to receive either placebo or 1 of 2 active doses of BCX7353. In the multiple dose cohort, twelve subjects will be treated with study drug (10 subjects will receive BCX7353 and 2 subjects will receive placebo per cohort). The planned doses (single and multiple dose cohort), and dosing regimen and duration of dosing (7 or 14 days; multple dose cohort) for Part 3 will be determined based upon safety and pharmacokinetic data collected during Parts 1 and 2 of the study.


Sponsor: BioCryst Pharmaceuticals

Current Primary Outcome:

  • Adverse events [ Time Frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration) ]
  • Laboratory analyses [ Time Frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration) ]
  • Vital signs [ Time Frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration) ]
  • Electrocardiograms [ Time Frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration) ]
  • Physical examination findings [ Time Frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration) ]


Original Primary Outcome:

  • Adverse events [ Time Frame: Part 1: through Study Day 7; Part 2: through 14 or 21 days (depending on dosing duration) ]
  • Laboratory analyses [ Time Frame: Part 1: through Study Day 7; Part 2: through 14 or 21 days (depending on dosing duration) ]
  • Vital signs [ Time Frame: Part 1: through Study Day 7; Part 2: through 14 or 21 days (depending on dosing duration) ]
  • Electrocardiograms [ Time Frame: Part 1: through Study Day 7; Part 2: through 14 or 21 days (depending on dosing duration) ]
  • Physical examination findings [ Time Frame: Part 1: through Study Day 7; Part 2: through 14 or 21 days (depending on dosing duration) ]


Current Secondary Outcome:

  • Plasma BCX7353 Cmax [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma BCX7353 Tmax [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma BCX7353 average steady-state concentration [ Time Frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma BCX7353 AUCinf [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort ]
  • Plasma BCX7353 AUCtau [ Time Frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma BCX7353 AUC0-t [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma BCX7353 t1/2 [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma BCX7353 apparent oral clearance [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma BCX7353 apparent volume of distribution [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma BCX7353 accumulation ratio [ Time Frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
  • Plasma pharmacodynamics of BCX7353 [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration) ]
    Outcome evaluated by change from baseline in ex vivo kallikrein inhibition


Original Secondary Outcome:

  • Plasma BCX7353 Cmax [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 Tmax [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 average steady-state concentration [ Time Frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 AUCinf [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 AUCtau [ Time Frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 AUC0-t [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 t1/2 [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 apparent oral clearance [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 apparent volume of distribution [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma BCX7353 accumulation ratio [ Time Frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
  • Plasma pharmacodynamics of BCX7353 [ Time Frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and through Day 11 or 21 for Part 2 (Day depends on dosing duration) ]
    Outcome evaluated by change from baseline in ex vivo kallikrein inhibition


Information By: BioCryst Pharmaceuticals

Dates:
Date Received: May 13, 2015
Date Started: May 2015
Date Completion:
Last Updated: January 12, 2016
Last Verified: January 2016