Study Of Palbociclib (PD-0332991) In Renal Impairment

A Phase 1, Open-label, Single Dose, Parallel-group Study To Evaluate The Pharmacokinetics Of Palbociclib (Pd-0332991) In Subjects With Impaired Renal Function

Since the amount of palbociclib eliminated in urine is 6.9%, renal impairment is not expected to have much impact on palbociclib. However, the Federal Drug Administration (FDA) Guidance recommends a study in subjects with renal impairment when the drug is likely to be used in patients with impaired renal function. Palbociclib is intended for chronic use in cancer patients who may have some degree of impaired renal function.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: palbociclib

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Personally signed and dated informed consent document.
• Renal function calculated by the Cockcroft Gault equation: normal function (CLcr >=90 mL/min), mild: CLcr >=60 mL/min and <90 mL/min, moderate: CLcr >=30 mL/min and <60 mL/min, severe: CLcr <30 mL/min but not requiring hemodialysis.
• Subjects with normal renal function matched for age, weight, gender and race to subjects in impaired renal function groups.

Exclusion Criteria:

• Any condition possibly affecting drug absorption.
• Renal allograft recipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Renal Impairment	Drug: palbociclib; palbociclib 125 mg oral capsule with food once
Experimental: Moderate Renal Impairment	Drug: palbociclib; palbociclib 125 mg oral capsule with food once
Experimental: Severe Renal Impairment	Drug: palbociclib; palbociclib 125 mg oral capsule with food once
Experimental: Normal Renal Function	Drug: palbociclib; palbociclib 125 mg oral capsule with food once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	8 days
Maximum Observed Plasma Concentration (Cmax)		8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	8 days
Apparent Oral Clearance (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	8 days
Time to Reach Maximum Observed Plasma Concentration (Tmax)		8 days
Apparent Volume of Distribution (Vz/F)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.	8 days
Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	8 days
Unbound Apparent Oral Clearance (CLu/F)	Clearance of unbound drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. Unbound drug clearance is a quantitative measure of the rate at which an unbound drug substance is removed from the blood.	8 days
"Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)u]"	AUC (0 - ∞)u= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞)u for unbound drug. It is obtained from AUC (0 - t)u plus AUC (t - ∞)u for unbound drug.	8 days
Unbound Maximum Observed Plasma Concentration (Cmaxu)	Cmaxu is the highest measured unbound plasma concentration during the dosing interval.	8 days
"Unbound Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu)"	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClastu) for unbound drug.	8 days
fraction of unbound drug in plasma (fu)	fraction of drug in plasma or tissues that is not bound to plasma or tissue proteins.	8 days
Unbound Apparent Volume of Distribution (Vzu/F)	Unbound Volume of distribution is defined as the theoretical volume in which the total unbound amount of drug would need to be uniformly distributed to produce the desired unbound plasma concentration of a drug. Unbound Apparent volume of distribution after oral dose (Vzu/F) is influenced by the fraction absorbed.	8 days

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: March 11, 2014
• First Submitted That Met QC Criteria: March 11, 2014
• First Posted (Estimate): March 13, 2014

Study Record Updates

• Last Update Posted (Actual): April 30, 2018
• Last Update Submitted That Met QC Criteria: April 26, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: renal impairment; AUC; Cmax; palbociclib; normal matched subjects
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: A5481014