Glasdegib Renal Impairment Study

NCT03596567 | Completed Phase 1 FDA Drug

• 1 other identifier: B1371017
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this study is to administer single dose (100 mg) glasdegib tablet to subjects with normal, moderate and severe renal impairment and estimate the effect, if any, of this renal impairment on glasdegib pharmacokinetics.

Conditions

Renal Impairment

Keywords

Glasdegib; PF-04449913; Pharmacokinetics; Renal Impairment

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax)

  6 days

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

  AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

  6 days

Secondary Outcomes (44)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).

  34 days

• PR/ECGs

  34 days

• Hematology Lab Panel

  34 days

• BUN /Chemistry Lab Panel

  34 days

• pH/Urinalysis Lab Panel

  34 days

Study Arms (3)

Normal Renal Function Group

EXPERIMENTAL

Subjects with estimated glomerular filtration rate (eGFR) of =\> 90 ml/min

Drug: Glasdegib single 100 mg dose in normal healthy subjects

Moderate Renal Impairment Group

EXPERIMENTAL

Subjects with estimated glomerular filtration rate (eGFR) of =\> 30ml/min and \< 60 ml/min

Drug: Glasdegib single 100 mg dose in moderate renal impairment subjects

Severe Renal Impairment Group

EXPERIMENTAL

Subjects with estimated glomerular filtration rate (eGFR) of \< 30 ml/min and not requiring dialysis

Drug: Glasdegib single 100 mg dose in severe renal impairment subjects

Interventions

Glasdegib single 100 mg dose in normal healthy subjects 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.

Normal Renal Function Group

Glasdegib single 100 mg dose in moderate renal impairment subjects DRUG

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

Moderate Renal Impairment Group

Glasdegib single 100 mg dose in severe renal impairment subjects DRUG

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

Severe Renal 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 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. 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 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.
• Subjects with Normal Renal Function will Need to Meet the Following Criteria in addition -
• Normal renal function, eGFR=\>90 mL/min, based on the MDRD equation.
• Matched for age (+/-10years) weight +/-15kg, and gender to subjects in the impaired renal function groups
• Subjects with Impaired Renal Function will Need to Meet the Following Criteria in Addition to Those Above
• Good general health commensurate with the population with chronic kidney disease (renal impairment). 'Health' is defined as no clinically relevant abnormalities (with the exception of hypertension, diabetes mellitus, hyperparathyroidism, ischemic heart disease, etc. as long as, in the opinion of the investigator, the subject is medically stable, is on a stable drug regimen and can abide by the meals and dietary restrictions outlined in protocol identified by a detailed medical history, full physical examination, measurement of pulse rate and 12 lead ECG as well as clinical laboratory tests (except serum creatinine and eGFR).
• Stable drug regimen defined as not starting a new drug or changing dosage within seven days or five half lives (whichever is longer) before dosing the study drug.
• Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).

You may not qualify if:

• Any condition possibly affecting drug absorption (eg, gastrectomy, achlorhydria).
• Renal allograft recipients
• Urinary incontinence without catheterization.
• Concurrent use of any of the following food or drugs known to inhibit CYP3A4 (consult the Sponsor if in doubt whether a food or a drug falls into any of the above categories) within 7 days or 5 half lives (whichever is longer) prior to the dose of glasdegib, until the completion of the last PK sample collection.
• Concurrent use of any of the following food or drugs known to induce CYP3A4 (consult the Sponsor if in doubt whether a food or a drug falls into any of the above categories) within 12 days or 5 half lives (whichever is longer) prior to the first dose of trial medication until the completion of the last PK sample collection.
• Pregnant female subjects; breastfeeding female subjects; fertile 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.
• Subjects with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level \> upper limit of normal (ULN);
• Total bilirubin level 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.
• For subjects with renal impairment, the following important additional criteria are:
• Screening blood pressure =\>180mm Hg (systolic) or\>=110 mm Hg (diastolic), following at least 5 minutes of supine rest. If initial blood pressure (BP) is 180 mm Hg (systolic) or 110 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.
• Screening supine 12 lead ECG demonstrating QTcF \>470 msec or a QRS interval \>120 msec. If initial QTcF exceeds 470 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF or QRS values should be used to determine the subject's eligibility.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

University of Miami Division of Clinical Pharmacology

Miami, Florida, 33136, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Prism Clinical Research LLC

Saint Paul, Minnesota, 55114, United States

Location

Related Publications (1)

• Shaik N, LaBadie RR, Hee B, Chan G. Evaluation of the impact of renal impairment on the pharmacokinetics of glasdegib in otherwise healthy volunteers. Cancer Chemother Pharmacol. 2021 Feb;87(2):241-250. doi: 10.1007/s00280-020-04207-9. Epub 2021 Jan 3.

  PMID: 33388951 DERIVED

Related Links

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

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

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: April 2, 2018
• First Posted: July 24, 2018
• Study Start: May 17, 2018
• Primary Completion: August 28, 2018
• Study Completion: September 19, 2018
• Last Updated: August 29, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)