Effect Of Itraconazole On The Pharmacokinetics Of Palbociclib

Study Overview
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Brief Summary
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This study is designed to evaluate the potential effect of itraconazole on the pharmacokinetics of palbociclib.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Palbociclib Alone
* Drug: Palbociclib plus itraconazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Fixed sequence<br>Fixed sequence study with treatment A of palbociclib alone, followed by treatment B (palbociclib with itraconazole) | Drug: Palbociclib Alone<br>* 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<br>* Other names: Palbociclib, PD-0332991;Drug: Palbociclib plus itraconazole<br>* 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.<br>* Other names: Palbociclib (PD-0332991); Itraconazole (Sporanox);|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palbociclib, Itraconazole, Pharmacokinetics, Drug-Drug Interaction Study, Healthy Volunteers