A Pharmacokinetic Study to Assess Drug-drug Interaction Between Zanubrutinib and a Cocktail of Substrates in Healthy Subjects

Healthy Subjects Clinical Trial

Official title:

An Open-label, Fixed-Sequence Study in Healthy Male Subjects to Assess the Drug Interaction Potential of Multiple Doses of Zanubrutinib With a Drug "Cocktail" Representative for CYP3A4, CYP2C9, CYP2C19, P-gP and BCRP Substrates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03561298
• Other study ID #: BGB-3111-108
• Status: Completed
• Phase: Phase 1
• Start date: June 7, 2018
• Est. completion date: July 2, 2018

Study information

• Verified date: October 2018
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the safety and pharmacokinetic interaction of effects of multiple doses of zanubrutinib with a "Cocktail" of five probe drugs for cytochrome P450 (CYP) 3A, CYP2C9, CYP2C19, P-glycoprotein and breast cancer resistance protein (BCRP) in healthy subjects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 2, 2018
• Est. primary completion date: June 7, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria: All Groups

• Male subjects in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening.

• Subjects must have a body mass index (BMI) between 18 and 32 kg/m2.

• Male subjects must agree to a highly effective method of birth control from screening until at least 90 days after the last dose of study drug.

Exclusion Criteria:

• Subjects with a clinically relevant history or presence of any clinically significant disease.

• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed).

• History of drug or alcohol abuse within 2 years prior to Check-In.

• Alcohol consumption of >21 units per week.

• A positive urine drug screen and/or positive alcohol breath test at Screening and/or Check-in.

• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result and/or a positive human immunodeficiency virus (HIV) at screening.

• Use of tobacco- or nicotine-containing products within 3 months prior to Check-In.

• History of blood donation of 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• BGB-3111 and Drug Cocktail
BGB-3111 and Drug Cocktail (midazolam, warfarin, omeprazole, digoxin and rosuvastatin)

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit	Daytona Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK parameters of probe drugs (warfarin, midazolam, digoxin, rosuvastatin, and omeprazole) derived from the plasma concentration time profile before and after oral administration of zanubrutinib	AUC from time 0 to the last quantifiable concentration (AUC0-t)	Days 1-20
Primary	PK parameters of probe drugs (warfarin, midazolam, digoxin, rosuvastatin, and omeprazole) derived from the plasma concentration time profile before and after oral administration of zanubrutinib	AUC from time 0 to infinity (AUC0 8; calculated as appropriate and allowed by the available data)	Days 1-20
Primary	PK parameters of probe drugs (warfarin, midazolam, digoxin, rosuvastatin, and omeprazole) derived from the plasma concentration time profile before and after oral administration of zanubrutinib	Maximum observed plasma concentration (Cmax)	Days 1-20
Primary	PK parameters of probe drugs (warfarin, midazolam, digoxin, rosuvastatin, and omeprazole) derived from the plasma concentration time profile before and after oral administration of zanubrutinib	Time of the maximum observed plasma concentration (Tmax)	Days 1-20
Secondary	Number of participants with adverse events as a measure of safety and tolerability.	An adverse event is an unfavorable and unintended sign (including an abnormal laboratory finding, an abnormal electrocardiogram), symptom or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.	up to 26 days