Clinical trial NCT02430545: Understanding The Effect Of A Strong CYP3A4 Inducer On Glasdegib Pharmacokinetics
Official title: A Phase 1, Open-label, Fixed-sequence, 2-period Study In Healthy Volunteers To Investigate The Effect Of Multiple Doses Of Rifampin On Single Dose Glasdegib (Pf-04449913) Plasma Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Glasdegib
PF-04449913
Drug-drug interaction
CYP3A4 inducer
Pharmacokinetics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-04-30
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 5 days
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]
timeFrame: 5 days
Secondary outcomes:
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: 5 days
measure: Apparent Oral Clearance (CL/F)
timeFrame: 5 days
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 5 days
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 5 days
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 5 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Shaik MN, Hee B, Wei H, LaBadie RR. Evaluation of the effect of rifampin on the pharmacokinetics of the Smoothened inhibitor glasdegib in healthy volunteers. Br J Clin Pharmacol. 2018 Jun;84(6):1346-1353. doi: 10.1111/bcp.13568. Epub 2018 Apr 10.