Back to results

An Open-label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 Enzyme Activity Using Probe Substrates

Primary Purpose

Hereditary Angioedema

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

BCX7353 and probes

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
Body mass index 18 to 32 kg/m2
Abides by study restrictions
Attends all study visits and agrees to remain in study center for the confinement period
Acceptable birth control measures for male subjects and women of childbearing potential

Key Exclusion Criteria:

Clinically significant medical history, current medical or psychiatric condition. This includes a history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, or cardiac disease
Clinically significant ECG finding, vital sign measurement or laboratory/urinalysis abnormality at screening or baseline
Poor or ultra- metabolizers of CYP2C19 or CYP2D6 Use of over the counter or prescription medication within 14 days of dosing and anticipated use through the follow-up visit
Use of medication or consumption of any substance 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 3 months
Serious adverse reaction or serious hypersensitivity to any drug

Sites / Locations

Quotient Clinical Ltd

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metabolic Probes and BCX7353

Arm Description

Day 1: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, and 30 mg dextromethorphan orally. Day 2: a single oral dose of 2 mg midazolam. Days 3 to 9: 350 mg BCX7353 once a day. Day 10: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, 30 mg dextromethorphan and 350 mg BCX7353, orally. Day 11: a single oral dose of 2 mg of midazolam along with 350 mg BCX7353.

Outcomes

Primary Outcome Measures

Cmax of probe substrates

Tmax of probe substrates

AUClast of probe substrates

AUCinf of probe substrates

t1/2 of probe substrates

Cl of intravenous midazolam

Secondary Outcome Measures

adverse events

laboratory analyses

Vital signs

physical examination findings

electrocardiograms

C24 for tolbutamide

C6 for IV and oral midazolam

Probe/metabolite AUC24 ratio

Tlag of probe substrates

VdF of probe substrates

CL/F of oral probe substrates

Vss of intravenous midazolam

Full Information

NCT ID

NCT02819102

First Posted

June 28, 2016

Last Updated

January 30, 2017

Sponsor

BioCryst Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02819102

Brief Title

An Open-label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 Enzyme Activity Using Probe Substrates

Official Title

A Single Sequence, Open-Label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 3A4, 2C9, 2C19 and 2D6 Enzyme Activity Using Probe Substrates in Healthy Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

June 2016

Overall Recruitment Status

Completed

Study Start Date

March 2016 (undefined)

Primary Completion Date

June 2016 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioCryst Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is an open-label, single sequence study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 enzymes using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353.

Detailed Description

This is a single centre, single sequence, open-label, study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 (CYP) 3A4 (midazolam IV and PO, respectively), CYP2C9 (tolbutamide), CYP2C19 (omeprazole) and CYP2D6 (dextromethorphan) enzyme activity using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353. Twenty healthy male and female subjects are planned for dosing. Each subject will receive the following treatments: Day 1: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, and 30 mg dextromethorphan orally. Day 2: a single oral dose of 2 mg midazolam. Days 3 to 9: 350 mg BCX7353 once a day. Day 10: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, 30 mg dextromethorphan and 350 mg BCX7353, orally. Day 11: a single oral dose of 2 mg of midazolam along with 350 mg BCX7353.

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

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Metabolic Probes and BCX7353

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

BCX7353 and probes

Primary Outcome Measure Information:

Title

Cmax of probe substrates

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

Tmax of probe substrates

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

AUClast of probe substrates

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

AUCinf of probe substrates

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

t1/2 of probe substrates

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

Cl of intravenous midazolam

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Secondary Outcome Measure Information:

Title

adverse events

Time Frame

absolute and change from baseline through study day 11

Title

laboratory analyses

Time Frame

absolute and change from baseline through study day 11

Title

Vital signs

Time Frame

absolute and change from baseline through study day 11

Title

physical examination findings

Time Frame

absolute and change from baseline through study day 11

Title

electrocardiograms

Time Frame

absolute and change from baseline through study day 11

Title

C24 for tolbutamide

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

C6 for IV and oral midazolam

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

Probe/metabolite AUC24 ratio

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

Tlag of probe substrates

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

VdF of probe substrates

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

CL/F of oral probe substrates

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

Title

Vss of intravenous midazolam

Time Frame

plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11

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 Body mass index 18 to 32 kg/m2 Abides by study restrictions Attends all study visits and agrees to remain in study center for the confinement period Acceptable birth control measures for male subjects and women of childbearing potential Key Exclusion Criteria: Clinically significant medical history, current medical or psychiatric condition. This includes a history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, or cardiac disease Clinically significant ECG finding, vital sign measurement or laboratory/urinalysis abnormality at screening or baseline Poor or ultra- metabolizers of CYP2C19 or CYP2D6 Use of over the counter or prescription medication within 14 days of dosing and anticipated use through the follow-up visit Use of medication or consumption of any substance 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 3 months Serious adverse reaction or serious hypersensitivity to any drug

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Litza McKenzie, MBChB

Organizational Affiliation

Quotient Clinical Ltd

Official's Role

Principal Investigator

Facility Information:

Facility Name

Quotient Clinical Ltd

City

Ruddington

State/Province

Nottingham

ZIP/Postal Code

NG11 6JS

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

An Open-label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 Enzyme Activity Using Probe Substrates

We'll reach out to this number within 24 hrs