A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions

Hereditary Angioedema Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03136237
• Other study ID #: BCX7353-105
• Status: Completed
• Phase: Phase 1
• First received: April 24, 2017
• Last updated: October 24, 2017
• Start date: February 17, 2017
• Est. completion date: August 15, 2017

Study information

• Verified date: October 2017
• Source: BioCryst Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: August 15, 2017
• Est. primary completion date: August 15, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• BCX7353
Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3
• Digoxin
Day 1 of Cohort 1
• BCX7353 + digoxin
Day 19 of Cohort 1
• Rosuvastatin
Day 1 of Cohort 2
• rosuvastatin + BCX7353
Day 15 of Cohort 1
• Cyclosporine + BCX7353
Day 14 of Cohort 3

Locations

Country	Name	City	State
United Kingdom	Covance CRU	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
BioCryst Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax of probe substrate		plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period
Primary	AUClast of probe substrate		plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period
Primary	AUCinf of probe substrate		plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period
Secondary	adverse events		absolute and change from baseline through end of study, approximately 30 days
Secondary	laboratory analyses		absolute and change from baseline through end of study, approximately 30 days
Secondary	vital signs		absolute and change from baseline through end of study, approximately 30 days
Secondary	physical examination findings		absolute and change from baseline through end of study, approximately 30 days
Secondary	electrocardiograms		absolute and change from baseline throughend of study, approximately 30 days