Healthy Volunteers
Conditions
Keywords
Glasdegib, PF-04449913, Drug-drug interaction, CYP3A4 inducer, Pharmacokinetics
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.
Interventions
DRUGGlasdegib
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
DRUGRifampin
Subjects receive rifampin 600 mg oral dose daily \[Day -6 to day 4\]
Sponsors
Pfizer
Study design
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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. * Female subjects of non childbearing potential must meet at least one of the following criteria: 1. 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; 2. Have undergone a documented hysterectomy and/or bilateral oophorectomy; 3. Have medically confirmed ovarian failure. * All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential. * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs). * Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. * Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) | 5 days |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | 5 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5 days | — |
| 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) |
| 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. |
| 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. |
| 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. |
Countries
United States
Outcome results
None listed