Glasdegib Absolute Bioavailability Study

Study Overview
=================
Brief Summary
-----------------
This study is intended to estimate the absolute bioavailability of Glasdegib by comparison of the pharmacokinetic exposures following administration of an oral, single dose 100 mg tablet vs. an IV infusion of a 50 mg IV dose in the fasted state in a crossover fashion to healthy volunteers.

Official Title
-----------------
A Phase One, Single Dose, Randomized, Open-label, Two-period, Two-sequence, Crossover, Absolute Bioavailability Study Of Glasdegib (Pf-04449913) In Healthy Volunteers

Conditions
-----------------
Healthy Volunteer Study

Intervention / Treatment
-----------------
* Drug: Glasdegib Oral Tablet
* Drug: Glasdegib IV infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion Criteria: Healthy male and/or female subjects of non-child bearing potential 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 nonchildbearing potential must meet at least 1 of the following criteria: Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 24 consecutive months with no alternative pathological or physiological cause; with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state; Have undergone a documented hysterectomy and/or bilateral oophorectomy; Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) are 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 lb). 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 test. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS interval >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 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. Subjects should be within normal range of potassium, magnesium and corrected calcium calculation at screening. Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential; male subjects with partners currently pregnant; male subjects 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glasdegib Oral tablet then IV<br>Subjects will receive a single 100 mg oral tablet of glasdegib under fasted conditions in the first study period followed by washout. Then in the second period, a 50 mg IV solution will be infused over approximately 1.25 hours under fasted conditions. | Drug: Glasdegib Oral Tablet<br>* Subjects will receive a single 100 mg oral tablet of glasdegib under fasted conditions, either in study period 1 or 2, depending on randomization.<br>Drug: Glasdegib IV infusion<br>* Subjects will receive a 50 mg IV infusion of glasdegib over approximately 1.25 hours, in the fasted state, in either period 1 or 2 based on randomization.<br>|
| Experimental: Glasdegib IV solution followed by Oral tablet<br>Subjects will receive a 50 mg IV solution will be infused over approximately 1.25 hours in the fasted condition followed by washout in the first study period . Then in the second period, a single 100 mg oral tablet of glasdegib will be administered under fasted conditions | Drug: Glasdegib Oral Tablet<br>* Subjects will receive a single 100 mg oral tablet of glasdegib under fasted conditions, either in study period 1 or 2, depending on randomization.<br>Drug: Glasdegib IV infusion<br>* Subjects will receive a 50 mg IV infusion of glasdegib over approximately 1.25 hours, in the fasted state, in either period 1 or 2 based on randomization.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] |  | 5 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glasdegib, PF-04449913, Pharmacokinetics, Bioavailability