A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions

Sponsor

BioCryst Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03136237

Collaborator

(none)

Enrollment

Location

Arms

5.9

Actual Duration (Months)

9.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hereditary Angioedema	Drug: BCX7353 Drug: Digoxin Drug: BCX7353 + digoxin Drug: Rosuvastatin Drug: rosuvastatin + BCX7353 Drug: Cyclosporine + BCX7353	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

3 parallel treatment assessments3 parallel treatment assessments

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study to Evaluate the Effect of BCX7353 on the Single Dose Pharmacokinetics of the P-gp Substrate Digoxin and the BCRP Substrate Rosuvastatin and the Effect of the P-gp Inhibitor Cyclosporine on the Single Dose Pharmacokinetics of BCX7353

Actual Study Start Date :

Feb 17, 2017

Actual Primary Completion Date :

Aug 15, 2017

Actual Study Completion Date :

Aug 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Day 1: Digoxin 0.25 mg oral dose Day 11-18: BCX7353 350 mg oral dose Day 19: Digoxin 0.25 mg oral dose and BCX7353 350 mg oral dose Day 20-21: BCX7353 350 mg oral dose	Drug: BCX7353 Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3 Drug: Digoxin Day 1 of Cohort 1 Drug: BCX7353 + digoxin Day 19 of Cohort 1
Experimental: Cohort 2 Day 1: Rosuvastatin 10 mg oral dose Day 7-14: BCX7353 350 mg oral dose Day 15: Rosuvastatin 10 mg oral dose and BCX7353 350 mg oral dose Day 16: BCX7353 350 mg oral dose	Drug: BCX7353 Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3 Drug: Rosuvastatin Day 1 of Cohort 2 Drug: rosuvastatin + BCX7353 Day 15 of Cohort 1
Experimental: Cohort 3 Day 1: BCX7353 350 mg oral dose Day 14: single oral dose of Cyclosporine 600 mg and BCX7353 350 mg	Drug: BCX7353 Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3 Drug: Cyclosporine + BCX7353 Day 14 of Cohort 3

Arm

Intervention/Treatment

Experimental: Cohort 1

Day 1: Digoxin 0.25 mg oral dose Day 11-18: BCX7353 350 mg oral dose Day 19: Digoxin 0.25 mg oral dose and BCX7353 350 mg oral dose Day 20-21: BCX7353 350 mg oral dose

Drug: BCX7353

Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3

Drug: Digoxin

Day 1 of Cohort 1

Drug: BCX7353 + digoxin

Day 19 of Cohort 1

Experimental: Cohort 2

Day 1: Rosuvastatin 10 mg oral dose Day 7-14: BCX7353 350 mg oral dose Day 15: Rosuvastatin 10 mg oral dose and BCX7353 350 mg oral dose Day 16: BCX7353 350 mg oral dose

Drug: BCX7353

Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3

Drug: Rosuvastatin

Day 1 of Cohort 2

Drug: rosuvastatin + BCX7353

Day 15 of Cohort 1

Experimental: Cohort 3

Day 1: BCX7353 350 mg oral dose Day 14: single oral dose of Cyclosporine 600 mg and BCX7353 350 mg

Drug: BCX7353

Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3

Drug: Cyclosporine + BCX7353

Day 14 of Cohort 3

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

adverse events [absolute and change from baseline through end 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]
physical examination findings [absolute and change from baseline through end of study, approximately 30 days]
electrocardiograms [absolute and change from baseline throughend of study, approximately 30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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