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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02819102
Other study ID # BCX7353-102
Secondary ID
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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