Clinical trial NCT03136237: A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hereditary Angioedema
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-05-02
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3 parallel treatment assessments
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Cmax of probe substrate
timeFrame: plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period
measure: AUClast of probe substrate
timeFrame: plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period
measure: AUCinf of probe substrate
timeFrame: plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period
Secondary outcomes:
measure: adverse events
timeFrame: absolute and change from baseline through end of study, approximately 30 days
measure: laboratory analyses
timeFrame: absolute and change from baseline through end of study, approximately 30 days
measure: vital signs
timeFrame: absolute and change from baseline through end of study, approximately 30 days
measure: physical examination findings
timeFrame: absolute and change from baseline through end of study, approximately 30 days
measure: electrocardiograms
timeFrame: absolute and change from baseline throughend of study, approximately 30 days
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Covance CRU
Study officials:
affiliation: Covance Clinical
name: Firas Almazedi, MBChB, Msc, CPI
role: PRINCIPAL_INVESTIGATOR
References: