Glasdegib Absolute Bioavailability Study

NCT ID: NCT03270878

Last Updated: 2017-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-07
• Study Completion Date: 2017-10-30

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.

Conditions

Healthy Volunteer Study

Keywords

Glasdegib; PF-04449913; Pharmacokinetics; Bioavailability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Glasdegib Oral tablet then IV

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.

Group Type: EXPERIMENTAL

Glasdegib Oral Tablet

Intervention Type: DRUG

Subjects will receive a single 100 mg oral tablet of glasdegib under fasted conditions, either in study period 1 or 2, depending on randomization.

Glasdegib IV infusion

Intervention Type: DRUG

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.

Glasdegib IV solution followed by Oral tablet

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

Group Type: EXPERIMENTAL

Glasdegib Oral Tablet

Intervention Type: DRUG

Subjects will receive a single 100 mg oral tablet of glasdegib under fasted conditions, either in study period 1 or 2, depending on randomization.

Glasdegib IV infusion

Intervention Type: DRUG

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.

Interventions

Glasdegib Oral Tablet

Subjects will receive a single 100 mg oral tablet of glasdegib under fasted conditions, either in study period 1 or 2, depending on randomization.

Intervention Type: DRUG

Glasdegib IV infusion

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.

Intervention Type: DRUG

Eligibility 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:

1. 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;

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 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

New Haven Clinical Research Unit

New Haven, Connecticut, United States

Countries

United States

References

Shaik N, Hee B, Liang Y, LaBadie RR. Absolute Oral Bioavailability of Glasdegib (PF-04449913), a Smoothened Inhibitor, in Randomized Healthy Volunteers. Clin Pharmacol Drug Dev. 2019 Oct;8(7):895-902. doi: 10.1002/cpdd.692. Epub 2019 Apr 12.

Reference Type: DERIVED

PMID: 30977980 (View on PubMed)

Related Links

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1371022&StudyName=A+Phase+One%2C+Single+Dose%2C+Randomized%2C+Open-label%2C+Two-period%2C+Two-sequence%2C+Crossover%2C+Absolute+Bioavailability+Study+Of+Glasdegib+%28pf-04449913%29+In+Healthy+Volunteers

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Other Identifiers

B1371022

Identifier Type: -

Identifier Source: org_study_id