A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions

BioCryst

Status and phase: Completed; Phase 1

Conditions: Hereditary Angioedema

Treatments: Drug: BCX7353; Drug: Rosuvastatin; Drug: rosuvastatin + BCX7353; Drug: Cyclosporine + BCX7353; Drug: Digoxin; Drug: BCX7353 + digoxin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03136237

BCX7353-105

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 3 patient groups

Cohort 1

Experimental group

Description:

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

Treatment:

Drug: BCX7353 + digoxin

Drug: BCX7353

Drug: Digoxin

Cohort 2

Experimental group

Description:

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

Treatment:

Drug: rosuvastatin + BCX7353

Drug: Rosuvastatin

Drug: BCX7353

Cohort 3

Experimental group

Description:

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

Treatment:

Drug: BCX7353

Drug: Cyclosporine + BCX7353