Healthy
Conditions
Keywords
PD-0332991, palbociclib, tamoxifen, drug-drug interaction (DDI) study
Brief summary
A single 125 mg oral dose of the investigational compound PD-0332991 will be administered alone and after steady-state dosing of tamoxifen to determine if coadministration of tamoxifen alters the plasma pharmacokinetics of PD-0332991 in healthy male volunteers.
Interventions
DRUGPD-0332991 alone
PD-0332991 is administered alone as a single oral 125 mg dose on Day 1 of Period 1.
DRUGTamoxifen 60 mg
On Days 1-4 of Period 2, tamoxifen is administered daily as 60 mg oral doses (using three 20mg tablets).
DRUGTamoxifen 20 mg
On Days 5-27 of Period 2, tamoxifen is administered daily as 20 mg oral doses.
DRUGPD-0332991 combination
PD-0332991 is administered in combination with tamoxifen on Day 22 of Period 2 as a single 125 mg oral dose.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male between the ages of 18 and 55 years of age inclusive * Body mass index (BMI) between 17.5 and 30.5 kg/m2 * Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion criteria
* a positive urine drug screen * a supine systolic blood pressure \>140 mm Hg, or diastolic blood pressure \>90 mm H. * Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of PD-0332991 | 0-144 hrs post PD-0332991 dose | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of PD-0332991 | 0-144 hrs post PD-0332991 dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991 | 0-144 hrs post PD-0332991 dose | — |
| Plasma Decay Half-Life (t1/2) of PD-0332991 | 0-144 hrs post PD-0332991 dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Apparent Oral Clearance (CL/F) of PD-0332991 | 0-144 hrs post PD-0332991 dose | 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) of PD-0332991 | 0-144 hrs post PD-0332991 dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Minimum Observed Plasma Trough Concentration (Cmin) of tamoxifen | Days 1, 5, 12, 21, 22, and 28 of Period 2 | — |
| Minimum Observed Plasma Trough Concentration (Cmin) of 4-hydroxytamoxifen | Days 1, 5, 12, 21, 22, and 28 of Period 2 | — |
| Minimum Observed Plasma Trough Concentration (Cmin) of N-desmethyltamoxifen | Days 1, 5, 12, 21, 22, and 28 of Period 2 | — |
| Minimum Observed Plasma Trough Concentration (Cmin) of endoxifen | Days 1, 5, 12, 21, 22, and 28 of Period 2 | — |
| Apparent Volume of Distribution (Vz/F) of PD-0332991 | 0-144 hrs post PD-0332991 dose | 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. |
Countries
United States
Outcome results
None listed