Understanding The Effect Of A Strong CYP3A4 Inducer On Glasdegib Pharmacokinetics
- Registration Number
- NCT02430545
- Lead Sponsor
- Pfizer
- Brief Summary
The study also aims to determine the effect of a strong enzyme (CYP3A4) inducer-rifampin- on drug exposure of Glasdegib. This study will be conducted in healthy subjects given a single dose of glasdegib in each period.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
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Healthy female subjects of non-childbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG or clinical laboratory tests.
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Female subjects of non childbearing potential must meet at least one of the following criteria:
- Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; AND have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state;
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- Have medically confirmed ovarian failure.
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All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential.
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Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
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Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
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Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
- A positive urine drug screen
- Screening supine 12 lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
- Subjects with family history of myocardial infarction, congenital long QT syndrome, torsades de pointes or clinically significant ventricular arrhythmias.
- Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use two highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of investigational product and, refrain from sperm donation for the duration of the study and for at least 90 days after the last dose of investigational product.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Glasdegib, Rifampin Rifampin Subjects receive a 100mg oral dose of glasdegib under fasted conditions with washout, then single 100mg oral dose of glasdegib under fasted following dosing to steady state with rifampin Glasdegib, Rifampin Glasdegib Subjects receive a 100mg oral dose of glasdegib under fasted conditions with washout, then single 100mg oral dose of glasdegib under fasted following dosing to steady state with rifampin
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) 5 days Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] 5 days
- Secondary Outcome Measures
Name Time Method Time to Reach Maximum Observed Plasma Concentration (Tmax) 5 days Apparent Volume of Distribution (Vz/F) 5 days Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Plasma Decay Half-Life (t1/2) 5 days Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 5 days Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Apparent Oral Clearance (CL/F) 5 days Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Trial Locations
- Locations (1)
New Haven Clinical Research Unit
🇺🇸New Haven, Connecticut, United States