A Study To Determine If Coadministration Of Tamoxifen Alters The Extent Or Rate Of Palbociclib (PD-0332991) Absorption Or Elimination In Healthy Male Volunteers
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT01821066
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 25
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Two-Period Fixed-Sequence Arm Tamoxifen 60 mg This arm is comprised of two treatment periods in fixed sequence. Period 1 is 7 days long, while Period 2 is 28 days long. In Period 1 the subjects receive a single 125 mg oral dose of PD-0332991 on Day 1. In Period 2 the subjects receive 4 daily 60 mg oral doses of tamoxifen (Days 1-4), followed by 23 daily 20 mg oral doses of tamoxifen (Days 5-27). On Day 22 of Period 2 the subjects receive a second 125 mg oral dose of PD-0332991. Two-Period Fixed-Sequence Arm PD-0332991 alone This arm is comprised of two treatment periods in fixed sequence. Period 1 is 7 days long, while Period 2 is 28 days long. In Period 1 the subjects receive a single 125 mg oral dose of PD-0332991 on Day 1. In Period 2 the subjects receive 4 daily 60 mg oral doses of tamoxifen (Days 1-4), followed by 23 daily 20 mg oral doses of tamoxifen (Days 5-27). On Day 22 of Period 2 the subjects receive a second 125 mg oral dose of PD-0332991. Two-Period Fixed-Sequence Arm Tamoxifen 20 mg This arm is comprised of two treatment periods in fixed sequence. Period 1 is 7 days long, while Period 2 is 28 days long. In Period 1 the subjects receive a single 125 mg oral dose of PD-0332991 on Day 1. In Period 2 the subjects receive 4 daily 60 mg oral doses of tamoxifen (Days 1-4), followed by 23 daily 20 mg oral doses of tamoxifen (Days 5-27). On Day 22 of Period 2 the subjects receive a second 125 mg oral dose of PD-0332991. Two-Period Fixed-Sequence Arm PD-0332991 combination This arm is comprised of two treatment periods in fixed sequence. Period 1 is 7 days long, while Period 2 is 28 days long. In Period 1 the subjects receive a single 125 mg oral dose of PD-0332991 on Day 1. In Period 2 the subjects receive 4 daily 60 mg oral doses of tamoxifen (Days 1-4), followed by 23 daily 20 mg oral doses of tamoxifen (Days 5-27). On Day 22 of Period 2 the subjects receive a second 125 mg oral dose of PD-0332991.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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 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)
Maximum Observed Plasma Concentration (Cmax) of PD-0332991 0-144 hrs post PD-0332991 dose Minimum Observed Plasma Trough Concentration (Cmin) of tamoxifen Days 1, 5, 12, 21, 22, and 28 of Period 2 Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991 0-144 hrs post PD-0332991 dose 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.
Minimum Observed Plasma Trough Concentration (Cmin) of endoxifen Days 1, 5, 12, 21, 22, and 28 of Period 2
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇺🇸New Haven, Connecticut, United States