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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

Registration Number
NCT02059330
Lead Sponsor
Pfizer
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
27
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Healthy Subjects of Japanese DescentPalbociclib 125mgEnrolled Japanese subjects will receive four palbociclib single doses of differing dose amounts in fixed sequence over four treatment periods.
Healthy Subjects of Japanese DescentPalbociclib 100mgEnrolled Japanese subjects will receive four palbociclib single doses of differing dose amounts in fixed sequence over four treatment periods.
Healthy Subjects of Japanese DescentPalbociclib 75mgEnrolled Japanese subjects will receive four palbociclib single doses of differing dose amounts in fixed sequence over four treatment periods.
Healthy Non-Asian SubjectsPalbociclib 125mgEnrolled healthy non-Asian subjects will receive a single 125mg oral dose of palbociclib in a single treatment period.
Healthy Subjects of Japanese DescentPalbociclibEnrolled Japanese subjects will receive four palbociclib single doses of differing dose amounts in fixed sequence over four treatment periods.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

New Haven, Connecticut, United States

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