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

Hereditary Angioedema Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02819102
• Other study ID #: BCX7353-102
• Status: Completed
• Phase: Phase 1
• First received: June 28, 2016
• Last updated: January 30, 2017
• Start date: March 2016
• Est. completion date: June 2016

Study information

• Verified date: June 2016
• Source: BioCryst Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• BCX7353 and probes

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical Ltd	Ruddington	Nottingham

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 substrates		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Primary	Tmax of probe substrates		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Primary	AUClast of probe substrates		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Primary	AUCinf of probe substrates		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Primary	t1/2 of probe substrates		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Primary	Cl of intravenous midazolam		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Secondary	adverse events		absolute and change from baseline through study day 11
Secondary	laboratory analyses		absolute and change from baseline through study day 11
Secondary	Vital signs		absolute and change from baseline through study day 11
Secondary	physical examination findings		absolute and change from baseline through study day 11
Secondary	electrocardiograms		absolute and change from baseline through study day 11
Secondary	C24 for tolbutamide		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Secondary	C6 for IV and oral midazolam		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Secondary	Probe/metabolite AUC24 ratio		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Secondary	Tlag of probe substrates		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Secondary	VdF of probe substrates		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Secondary	CL/F of oral probe substrates		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Secondary	Vss of intravenous midazolam		plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11