Understanding The Effect Of A Strong CYP3A4 Inducer On Glasdegib Pharmacokinetics

NCT02430545 | Completed Phase 1

• 1 other identifier: B1371015
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Glasdegib; PF-04449913; Drug-drug interaction; CYP3A4 inducer; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax)

  5 days

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

  5 days

Secondary Outcomes (5)

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

  5 days

• Apparent Oral Clearance (CL/F)

  5 days

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  5 days

• Apparent Volume of Distribution (Vz/F)

  5 days

• Plasma Decay Half-Life (t1/2)

  5 days

Study Arms (1)

Glasdegib, Rifampin

EXPERIMENTAL

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

Drug: Glasdegib; Drug: Rifampin

Interventions

Glasdegib DRUG

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

Glasdegib, Rifampin

Rifampin DRUG

Subjects receive rifampin 600 mg oral dose daily \[Day -6 to day 4\]

Glasdegib, Rifampin

Eligibility Criteria

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

You may qualify if:

• 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:
• 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;
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

• 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.

  PMID: 29488303 DERIVED

MeSH Terms

Interventions

glasdegib; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 27, 2015
• First Posted: April 30, 2015
• Study Start: May 1, 2015
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 25, 2015

Record last verified: 2015-06

Locations

US (1)