A Study Of Glasdegib In Healthy Volunteers To Establish The Bioequivalence Of The Phase 2 Formulation To The ICH Formulation

NCT03130556 | Completed Phase 1 FDA Drug

• 1 other identifier: B1371026
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is intended to establish the bioequivalence (BE) of single 100 mg doses of glasdegib administered under fasted conditions to healthy volunteers as the ICH formulation compared to the Phase 2 formulation.

Conditions

Healthy Volunteers

Keywords

Glasdegib; PF-04449913; Pharmacokinetics; Bioavailability

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax)

  5 days

• Area Under the Curve From Time Zero to Last Measured Time Point [AUC (0 - t)]

  5 days

Secondary Outcomes (1)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]

  5 days

Study Arms (2)

Glasdegib BE and Food

EXPERIMENTAL

Subjects receive 100 mg single dose of ICH glasdegib under fasted condition with washout and then 100 mg single dose of Phase 2 tablet under fasted condition with washout in a randomized fashion. Finally subjects receive a 100 mg single dose ICH tablet after a high fat, high calorie meal.

Drug: Glasdegib; Other: High Fat, High Calorie Meal

Glasdegib BE and PPI Effect

EXPERIMENTAL

Subjects receive 100 mg single dose of ICH glasdegib under fasted condition with washout and then 100 mg single dose of Phase 2 tablet under fasted condition with washout in a randomized fashion. Finally subjects receive a 100 mg single dose ICH tablet in the fasted state after repeated daily dosing with rabeprazole.

Drug: Glasdegib; Drug: Rabeprazole

Interventions

Glasdegib DRUG

Subjects receive 100 mg single dose of ICH glasdegib under fasted condition with washout and then 100 mg single dose of Phase 2 tablet under fasted condition with washout in a randomized fashion. Finally subjects either receive a 100 mg single dose ICH tablet after a high fat, high calorie meal or receive a 100 mg single dose of ICH tablet after repeated daily dosing with rabeprazole.

Glasdegib BE and Food; Glasdegib BE and PPI Effect

High Fat, High Calorie Meal OTHER

A subset of subjects in the study will receive a high fat, high calorie meal prior to being administered a single 100 mg tablet ICH tablet of glasdegib.

Glasdegib BE and Food

Rabeprazole DRUG

A subset of subjects will receive repeated daily dosing of 40 mg rabeprazole for 7 days with 100 mg single dose of ICH glasdegib being administered on Day 7.

Glasdegib BE and PPI Effect

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

• Shaik N, Hee B, Wei H, LaBadie RR. Evaluation of the effects of formulation, food, or a proton-pump inhibitor on the pharmacokinetics of glasdegib (PF-04449913) in healthy volunteers: a randomized phase I study. Cancer Chemother Pharmacol. 2019 Mar;83(3):463-472. doi: 10.1007/s00280-018-3748-8. Epub 2018 Dec 10.

  PMID: 30536154 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

glasdegib; Rabeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2017
• First Posted: April 26, 2017
• Study Start: May 1, 2017
• Primary Completion: July 6, 2017
• Study Completion: July 21, 2017
• Last Updated: August 1, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)