Hereditary Angioedema
Conditions
Brief summary
This is an open-label, three part study to evaluate the effect of BCX7353 on drug transporters as well as the effect of an inhibitor of drug transport on BCX7353.
Detailed description
This is a single center, open-label, fixed-sequence, drug interaction study to evaluate the effect of BCX7353 on the pharmacokinetics of the P-gp substrate digoxin and the BCRP substrate rosuvastatin, as well as the effect of the P-gp inhibitor cyclosporine on the pharmacokinetics of BCX7353. It is planned that 54 subjects will be enrolled into 3 cohorts of 18 subjects each. Cohort 1 will evaluate the effects of multiple doses of BCX7353 on single-dose pharmacokinetics of digoxin. Cohort 2 will evaluate the effect of multiple doses of BCX7353 on the pharmacokinetics of rosuvastatin. Cohort 3 will evaluate the effect of a single dose of cyclosporine on the pharmacokinetics of BCX7353. Cohorts may be dosed in parallel or in any order.
Interventions
DRUGBCX7353
Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3
DRUGDigoxin
Day 1 of Cohort 1
DRUGBCX7353 + digoxin
Day 19 of Cohort 1
DRUGRosuvastatin
Day 1 of Cohort 2
DRUGrosuvastatin + BCX7353
Day 15 of Cohort 1
DRUGCyclosporine + BCX7353
Day 14 of Cohort 3
Sponsors
BioCryst Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3 parallel treatment assessments
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * written informed consent * acceptable birth control measures for male subjects and women of childbearing potential * creatinine clearance of at least 80 mL/min by Cockcroft-Gault equation * complies with all required study procedures and restrictions Key
Exclusion criteria
* clinically significant medical history, current medical or psychiatric condition * clinically significant ECG finding, vital sign measurement or laboratory/urinalysis abnormality at screening or baseline * current use, or use of any prescribed or over the counter medication, vitamins or herbal products within 14 days of Day 1 * use of medication 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 the previous 3 months * history of severe hypersensitivity to any medicinal product * for subjects enrolled in cohort 1, current use of antibiotics or probiotics, or use within 6 months prior to Day 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax of probe substrate | plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period |
| AUClast of probe substrate | plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period |
| AUCinf of probe substrate | plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period |
Secondary
| Measure | Time frame |
|---|---|
| physical examination findings | absolute and change from baseline through end of study, approximately 30 days |
| adverse events | absolute and change from baseline through end of study, approximately 30 days |
| electrocardiograms | absolute and change from baseline throughend of study, approximately 30 days |
| laboratory analyses | absolute and change from baseline through end of study, approximately 30 days |
| vital signs | absolute and change from baseline through end of study, approximately 30 days |
Countries
United Kingdom
Outcome results
None listed