A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Drug: BCX7353
* Drug: Digoxin
* Drug: BCX7353 + digoxin
* Drug: Rosuvastatin
* Drug: rosuvastatin + BCX7353
* Drug: Cyclosporine + BCX7353


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3 parallel treatment assessments
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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<br>* Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3<br>Drug: Digoxin<br>* Day 1 of Cohort 1<br>Drug: BCX7353 + digoxin<br>* Day 19 of Cohort 1<br>|
| Experimental: Cohort 2<br>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<br>* Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3<br>Drug: Rosuvastatin<br>* Day 1 of Cohort 2<br>Drug: rosuvastatin + BCX7353<br>* Day 15 of Cohort 1<br>|
| Experimental: Cohort 3<br>Day 1: BCX7353 350 mg oral dose Day 14: single oral dose of Cyclosporine 600 mg and BCX7353 350 mg | Drug: BCX7353<br>* Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3<br>Drug: Cyclosporine + BCX7353<br>* Day 14 of Cohort 3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |