Healthy
Conditions
Keywords
Japanese PK-Bridging Study, dose-proportionality study, Palbociclib, PD-0332991, healthy volunteers
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.
Interventions
DRUGPalbociclib 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.
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.
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.
DRUGPalbociclib
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.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) |
| 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. |
| 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. |
Countries
United States
Outcome results
None listed