Clinical trial NCT03561298: A Pharmacokinetic Study to Assess Drug-drug Interaction Between Zanubrutinib and a Cocktail of Substrates in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Pharmacokinetics
Healthy subjects
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-06-19
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Days 1-20
measure: 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
timeFrame: Days 1-20
measure: 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
timeFrame: Days 1-20
measure: 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
timeFrame: Days 1-20
Secondary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerability.
timeFrame: up to 26 days
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Clinical Research Unit
state: Florida
Study officials:
affiliation: BeiGene
name: William Novotny, MD
role: STUDY_DIRECTOR
References: