A Study To Investigate Palbociclib (PD-0332991) Pharmacokinetics In Healthy Subjects Of Japanese Descent Relative To Healthy Non-Asian Subjects, And To Determine If Changes In Palbociclib Dose Result In Proportional Changes In Palbociclib Plasma Exposure In Japanese Subjects

Study Overview
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Brief Summary
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This study will investigate the dose-proportionality of palbociclib pharmacokinetics in healthy subjects of Japanese descent. Approximately fourteen healthy Japanese subjects will receive four single doses of palbociclib (PD-0332991) with a minimum washout of 10 days between doses. Additionally, this study will investigate the effect of Japanese ethnicity of palbociclib pharmacokinetics by comparing palbociclib pharmacokinetics at a single dose-level between healthy subjects of Japanese descent and approximately fourteen healthy non-Asian subjects.

Official Title
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A Phase 1, Open Label Study To Investigate The Effect Of Dose And Ethnicity On Palbociclib (PD-0332991) Pharmacokinetics In Japanese Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Palbociclib 75mg
* Drug: Palbociclib 125mg
* Drug: Palbociclib 100mg
* Drug: Palbociclib
* Drug: Palbociclib 125mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be a healthy male or female of non-childbearing potential Subjects must have a BMI (Body Mass Index) between 17.5 and 30.5 kg/m2 To be eligible for the Japanese cohort, subjects must have 4 biological grandparents who are Japanese that were born in Japan Exclusion Criteria: Any condition affecting drug absorption (eg gastrectomy, achlorhydria, etc) Use of prescription or non-prescription drugs A QTc-interval >450msec or a QRS interval >120msec Pregnant or breastfeeding females, females of childbearing potential, and males who are unwilling or unable to use an effective method of contraception for the duration of the study and for 90 days after the last dose of palbociclib in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Healthy Subjects of Japanese Descent<br>Enrolled Japanese subjects will receive four palbociclib single doses of differing dose amounts in fixed sequence over four treatment periods. | Drug: Palbociclib 75mg<br>* In Period 1, Japanese subjects will receive a single oral 75mg dose of palbociclib with food. Serial PK assessments will be collected over the next 120 hours.<br>* Other names: PD-0332991;Drug: Palbociclib 125mg<br>* In Period 2, Japanese subjects will receive a single oral 125mg dose of palbociclib with food. Serial PK assessments will be collected over the next 120 hours.<br>* Other names: PD-0332991;Drug: Palbociclib 100mg<br>* In Period 3, Japanese subjects will receive a single oral 100mg dose of palbociclib with food. Serial PK assessments will be collected over the next 120 hours.<br>* Other names: PD-0332991;Drug: Palbociclib<br>* In Period 4, Japanese subjects will receive a single oral dose of palbociclib with food. Serial PK assessments will be collected over the next 120 hours. The amount of the dose will be determined based on an interim analysis of the PK data from Periods 1 and 2.<br>* Other names: PD-0332991;|
| Experimental: Healthy Non-Asian Subjects<br>Enrolled healthy non-Asian subjects will receive a single 125mg oral dose of palbociclib in a single treatment period. | Drug: Palbociclib 125mg<br>* In Period 1, healthy non-Asian subjects will receive a single oral 125mg dose of palbociclib with food. Serial PK assessments will be collected over the next 120 hours.<br>* Other names: PD-0332991;|

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). | 0-120 hours | 
| Dose-normalised Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | AUC (0 - 8)DN= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8) divided by dose. It is obtained from AUC (0 - t) plus AUC (t - 8) all divided by the administered dose. | 0-120 hours | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0-120 hours | 
| Dose-Normalised Maximum Observed Plasma Concentration (Cmax) |  | 0-120 hours | 

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) | 0-120 hours | 
| Dose-Normalized 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), all divided by the administered dose. | 0-120 hours | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0-120 hours | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0-120 hours | 
| 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. | 0-120 hours | 
| 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. | 0-120 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese PK-Bridging Study, dose-proportionality study, Palbociclib, PD-0332991, healthy volunteers