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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT02059330

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

8.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Palbociclib 75mg Drug: Palbociclib 125mg Drug: Palbociclib 100mg Drug: Palbociclib Drug: Palbociclib 125mg	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Mar 1, 2014

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy Subjects of Japanese Descent Enrolled Japanese subjects will receive four palbociclib single doses of differing dose amounts in fixed sequence over four treatment periods.	Drug: Palbociclib 75mg 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. Other Names: PD-0332991 Drug: Palbociclib 125mg 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. Other Names: PD-0332991 Drug: Palbociclib 100mg 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. Other Names: PD-0332991 Drug: Palbociclib 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. Other Names: PD-0332991
Experimental: Healthy Non-Asian Subjects Enrolled healthy non-Asian subjects will receive a single 125mg oral dose of palbociclib in a single treatment period.	Drug: Palbociclib 125mg 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. Other Names: PD-0332991

Arm

Intervention/Treatment

Experimental: Healthy Subjects of Japanese Descent

Enrolled Japanese subjects will receive four palbociclib single doses of differing dose amounts in fixed sequence over four treatment periods.

Drug: Palbociclib 75mg

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.

Other Names:

PD-0332991

Drug: Palbociclib 125mg

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.

Other Names:

PD-0332991

Drug: Palbociclib 100mg

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.

Other Names:

PD-0332991

Drug: Palbociclib

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.

Other Names:

PD-0332991

Experimental: Healthy Non-Asian Subjects

Enrolled healthy non-Asian subjects will receive a single 125mg oral dose of palbociclib in a single treatment period.

Drug: Palbociclib 125mg

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.

Other Names:

PD-0332991

Outcome Measures

Primary Outcome Measures

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [0-120 hours]
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).
Dose-normalised Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [0-120 hours]
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.
Maximum Observed Plasma Concentration (Cmax) [0-120 hours]
Dose-Normalised Maximum Observed Plasma Concentration (Cmax) [0-120 hours]

Secondary Outcome Measures

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [0-120 hours]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [0-120 hours]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast), all divided by the administered dose.
Time to Reach Maximum Observed Plasma Concentration (Tmax) [0-120 hours]
Plasma Decay Half-Life (t1/2) [0-120 hours]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Apparent Oral Clearance (CL/F) [0-120 hours]
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.
Apparent Volume of Distribution (Vz/F) [0-120 hours]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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