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A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions

Primary Purpose

Hereditary Angioedema

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

BCX7353

Digoxin

BCX7353 + digoxin

Rosuvastatin

rosuvastatin + BCX7353

Cyclosporine + BCX7353

About this trial

This is an interventional treatment trial for Hereditary Angioedema

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Covance CRU

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm 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

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

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

Outcomes

Primary Outcome Measures

Cmax of probe substrate

AUClast of probe substrate

AUCinf of probe substrate

Secondary Outcome Measures

adverse events

laboratory analyses

vital signs

physical examination findings

electrocardiograms

Full Information

NCT ID

NCT03136237

First Posted

April 24, 2017

Last Updated

October 24, 2017

Sponsor

BioCryst Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03136237

Brief Title

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

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

February 17, 2017 (Actual)

Primary Completion Date

August 15, 2017 (Actual)

Study Completion Date

August 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioCryst Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hereditary Angioedema

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

3 parallel treatment assessments

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm 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

Arm Title

Cohort 2

Arm Type

Experimental

Arm 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

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

BCX7353

Intervention Description

Day 11-18 for Cohort 1, Day 7-14 for Cohort 2, Day 1 for Cohort 3

Intervention Type

Drug

Intervention Name(s)

Digoxin

Intervention Description

Day 1 of Cohort 1

Intervention Type

Drug

Intervention Name(s)

BCX7353 + digoxin

Intervention Description

Day 19 of Cohort 1

Intervention Type

Drug

Intervention Name(s)

Rosuvastatin

Intervention Description

Day 1 of Cohort 2

Intervention Type

Drug

Intervention Name(s)

rosuvastatin + BCX7353

Intervention Description

Day 15 of Cohort 1

Intervention Type

Drug

Intervention Name(s)

Cyclosporine + BCX7353

Intervention Description

Day 14 of Cohort 3

Primary Outcome Measure Information:

Title

Cmax of probe substrate

Time Frame

plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period

Title

AUClast of probe substrate

Time Frame

plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period

Title

AUCinf of probe substrate

Time Frame

plasma pharmacokinetic parameters are based on blood sampling over a 48 - 72 hour period

Secondary Outcome Measure Information:

Title

adverse events

Time Frame

absolute and change from baseline through end of study, approximately 30 days

Title

laboratory analyses

Time Frame

absolute and change from baseline through end of study, approximately 30 days

Title

vital signs

Time Frame

absolute and change from baseline through end of study, approximately 30 days

Title

physical examination findings

Time Frame

absolute and change from baseline through end of study, approximately 30 days

Title

electrocardiograms

Time Frame

absolute and change from baseline throughend of study, approximately 30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Firas Almazedi, MBChB, Msc, CPI

Organizational Affiliation

Covance Clinical

Official's Role

Principal Investigator

Facility Information:

Facility Name

Covance CRU

City

Leeds

ZIP/Postal Code

LS2 9LH

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions

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