A Study To Determine If Coadministration Of Tamoxifen Alters The Extent Or Rate Of Palbociclib (PD-0332991) Absorption Or Elimination In Healthy Male Volunteers

A Phase 1 Open-Label Fixed-Sequence Two-Period Crossover Study Of The Effect Of Multiple Doses Of Tamoxifen On PD-0332991 Pharmacokinetics In Healthy Male Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PD-0332991 alone; Drug: Tamoxifen 60 mg; Drug: Tamoxifen 20 mg; Drug: PD-0332991 combination

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Two-Period Fixed-Sequence Arm; 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.

Drug: PD-0332991 alone; PD-0332991 is administered alone as a single oral 125 mg dose on Day 1 of Period 1.; Other Names: PD-0332991, palbociclib; Drug: Tamoxifen 60 mg; On Days 1-4 of Period 2, tamoxifen is administered daily as 60 mg oral doses (using three 20mg tablets).; Drug: Tamoxifen 20 mg; On Days 5-27 of Period 2, tamoxifen is administered daily as 20 mg oral doses.; Drug: PD-0332991 combination; PD-0332991 is administered in combination with tamoxifen on Day 22 of Period 2 as a single 125 mg oral dose.; Other Names: PD-0332991, palbociclib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of PD-0332991	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).	0-144 hrs post PD-0332991 dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PD-0332991	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0-144 hrs post PD-0332991 dose
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	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0-144 hrs post PD-0332991 dose
Apparent Oral Clearance (CL/F) of PD-0332991	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.	0-144 hrs post PD-0332991 dose
Apparent Volume of Distribution (Vz/F) of PD-0332991	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.	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
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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: March 26, 2013
• First Submitted That Met QC Criteria: March 26, 2013
• First Posted (Estimate): March 29, 2013

Study Record Updates

• Last Update Posted (Estimate): October 8, 2015
• Last Update Submitted That Met QC Criteria: October 6, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: tamoxifen; PD-0332991; palbociclib; drug-drug interaction (DDI) study
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Palbociclib; Tamoxifen
• Other Study ID Numbers: A5481026