A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions

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

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.

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.

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