A Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of Glasdegib

NCT03627754 | Completed Phase 1 FDA Drug

• 1 other identifier: B1371016
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1, open-label, parallel group, single dose study to investigate the effect of moderate or severe hepatic impairment on the PK of glasdegib, compared to subjects with normal hepatic function.

Conditions

Hepatic Impairment

Keywords

Glasdegib; PF-04449913; Pharmacokinetics; Hepatic Impairment

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time curve from time 0 to infinity (AUCinf) of glasdegib

  PK parameter of glasdegib to be calculated from the plasma concentration-time data

  Day 1 to Day 6

• Maximum observed plasma concentration (Cmax) of glasdegib

  PK parameter of glasdegib to be calculated from the plasma concentration-time data

  Day 1

Secondary Outcomes (4)

• Incidence of adverse events

  Day 1 to Day 35

• Incidence of clinical laboratory abnormalities

  Day 1 to Day 35

• Incidence of vital sign abnormalities

  Day 1 to Day 35

• Incidence of clinical ECG abnormalities

  Day 1 to Day 35

Study Arms (3)

Moderate Hepatic Impairment Group

EXPERIMENTAL

Subjects with Child-Pugh Classification B (score 7-9)

Drug: Glasdegib 100 mg single oral dose

Severe Hepatic Impairment Group

EXPERIMENTAL

Subjects with Child-Pugh Classification C (score 10-15)

Drug: Glasdegib 100 mg single oral dose

Normal Hepatic Function Group

EXPERIMENTAL

Healthy subjects with normal hepatic function

Drug: Glasdegib 100 mg single oral dose

Interventions

Glasdegib 100 mg single oral dose DRUG

A single dose of 100 mg glasdegib tablet will be administered after an overnight fast, followed by serial PK collection, discharge and follow-up.

Moderate Hepatic Impairment Group; Normal Hepatic Function Group; Severe Hepatic Impairment Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy or hepatically impaired female subjects of non-child bearing potential and/or male subjects who, at the time of Screening, are between the ages of 18 and 75 years, inclusive.
• 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 12 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) are considered to be of childbearing potential.
• Body mass index (BMI) of 17.5 to 40 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 (or a legal representative) 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.
• No known or suspected hepatic impairment based on liver function tests, albumin and prothrombin time, defined as the following:
• ALT and AST \<= upper limit of normal (ULN);
• Total bilirubin \<= 1.5 × ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is not greater than 0.5 mg/dL;
• Alkaline phosphatase \<= ULN;
• Albumin within the normal range (local lab ranges);
• Prothrombin time (PT) within the normal range (local lab ranges).
• Subjects must fit the demographic-matching criteria, including:

You may not qualify if:

• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug test. Subjects with hepatic impairment (Cohorts 1 and 2) will be eligible to participate if their urine drug test is positive with a drug for a prescribed substance that is not expected to interfere with the PK of glasdegib.
• Pregnant female subjects; breastfeeding female subjects; fertile male subjects who are unwilling or unable to use at least one highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the glasdegib dose and, refrain from sperm donation for the duration of the Study and for at least 90 days after the glasdegib dose.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Blood donation of approximately 1 pint (500 mL) or more within 56 days prior to dosing.
• Unwilling or unable to comply with the Lifestyle Requirements.
• Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
• History of known sensitivity to glasdegib.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the dose of glasdegib (whichever is longer).
• Subjects with a history of or current positive results for human immunodeficiency virus (HIV).
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• In addition, subjects in the normal hepatic function cohort (Cohort 3) presenting with any of the following will not be included in the trial:
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies deemed relevant for participation in this study, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.
• Screening supine BP =\> 140 mm Hg (systolic) or =\> 90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is =\> 140 mm Hg (systolic) or =\> 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

Investigational Drug Services (IDS) University of Miami Hospitals and Clinics, Research Pharmacy

Miami, Florida, 33136, United States

Location

University of Miami Division of Clinical Pharmacology

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• Masters JC, LaBadie RR, Salageanu J, Li J, Shaik N. Pharmacokinetics and Safety of Glasdegib in Participants With Moderate/Severe Hepatic Impairment: A Phase I, Single-Dose, Matched Case-Control Study. Clin Pharmacol Drug Dev. 2021 Jul;10(7):707-717. doi: 10.1002/cpdd.897. Epub 2020 Dec 23.

  PMID: 33356019 DERIVED

Related Links

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

MeSH Terms

Interventions

glasdegib

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2018
• First Posted: August 13, 2018
• Study Start: November 5, 2018
• Primary Completion: April 11, 2019
• Study Completion: April 11, 2019
• Last Updated: May 6, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)