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

NCT02819102 | Completed Phase 1

• 1 other identifier: BCX7353-102
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Hereditary Angioedema

Outcome Measures

Primary Outcomes (6)

• Cmax of probe substrates

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

• Tmax of probe substrates

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

• AUClast of probe substrates

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

• AUCinf of probe substrates

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

• t1/2 of probe substrates

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

• Cl of intravenous midazolam

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

Secondary Outcomes (12)

• adverse events

  absolute and change from baseline through study day 11

• laboratory analyses

  absolute and change from baseline through study day 11

• Vital signs

  absolute and change from baseline through study day 11

• physical examination findings

  absolute and change from baseline through study day 11

• electrocardiograms

  absolute and change from baseline through study day 11

Study Arms (1)

Metabolic Probes and BCX7353

EXPERIMENTAL

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.

Drug: BCX7353 and probes

Interventions

BCX7353 and probes DRUG

Metabolic Probes and BCX7353

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BioCryst Pharmaceuticals: lead

Study Sites (1)

Quotient Clinical Ltd

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

berotralstat

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Study Officials

• Litza McKenzie, MBChB

  Quotient Clinical Ltd

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: June 30, 2016
• Study Start: March 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: January 31, 2017

Record last verified: 2016-06

Locations

GB (1)