Effect Of Itraconazole On The Pharmacokinetics Of Palbociclib

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT02131298

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

11.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to evaluate the potential effect of itraconazole on the pharmacokinetics of palbociclib.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Palbociclib Alone Drug: Palbociclib plus itraconazole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Phase 1, Open-Label, Fixed-Sequence 2-Period Study To Investigate The Effect Of Multiple Doses Of Itraconazole On The Single Dose Pharmacokinetics of Palbociclib (PD-0332991) In Healthy Volunteers

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: Fixed sequence Fixed sequence study with treatment A of palbociclib alone, followed by treatment B (palbociclib with itraconazole)	Drug: Palbociclib Alone A single 125 mg dose of palbociclib free base capsule given orally alone in the fed state, followed by 120 hours of PK sample collection Other Names: Palbociclib, PD-0332991 Drug: Palbociclib plus itraconazole Itraconazole 200 mg once daily with food for a total of 11 days; on Day 5, a single oral 125 mg dose of palbociclib will be given with itraconazole after a meal, followed by 168 hours of PK sample collection. Other Names: Palbociclib (PD-0332991); Itraconazole (Sporanox)

Arm

Intervention/Treatment

Other: Fixed sequence

Fixed sequence study with treatment A of palbociclib alone, followed by treatment B (palbociclib with itraconazole)

Drug: Palbociclib Alone

A single 125 mg dose of palbociclib free base capsule given orally alone in the fed state, followed by 120 hours of PK sample collection

Other Names:

Palbociclib, PD-0332991

Drug: Palbociclib plus itraconazole

Itraconazole 200 mg once daily with food for a total of 11 days; on Day 5, a single oral 125 mg dose of palbociclib will be given with itraconazole after a meal, followed by 168 hours of PK sample collection.

Other Names:

Palbociclib (PD-0332991); Itraconazole (Sporanox)

Outcome Measures

Primary Outcome Measures

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [0 to 168 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).
Maximum Observed Plasma Concentration (Cmax) [0 to 168 hours]

Secondary Outcome Measures

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [0 to 168 hours]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time to Reach Maximum Observed Plasma Concentration (Tmax) [0 to 168 hours]
Plasma Decay Half-Life (t1/2) [0 to 168 hours]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Apparent Oral Clearance (CL/F) [0 to 168 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 to 168 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive.
Body mass index of 17.5 to 30.5 kg/m2, and a total body weight >50 kg (110 lbs).
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic diseases.
Any condition possibly affecting drug absorption.
A positive urine drug screen or alcohol breath test.
Pregnant female subjects; breast feeding female subjects, female subjects of childbearing potential, male subjects with partners currently pregnant, male subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 90 days after the last dose of investigational product.