Study Of Palbociclib (PD-0332991) In Renal Impairment

Study Overview
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Brief Summary
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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.

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

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: palbociclib
* Drug: palbociclib
* Drug: palbociclib
* Drug: palbociclib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal Renal Function<br> | Drug: palbociclib<br>* palbociclib 125 mg oral capsule with food once<br>|
| Experimental: Mild Renal Impairment<br> | Drug: palbociclib<br>* palbociclib 125 mg oral capsule with food once<br>|
| Experimental: Moderate Renal Impairment<br> | Drug: palbociclib<br>* palbociclib 125 mg oral capsule with food once<br>|
| Experimental: Severe Renal Impairment<br> | Drug: palbociclib<br>* palbociclib 125 mg oral capsule with food once<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal impairment, AUC, Cmax, palbociclib, normal matched subjects