A Study To Investigate The Drug-Drug Interaction Potential Of Rifampin OnThe Investigational Agent Palbociclib (PD-0332991)

Study Overview
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Brief Summary
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This study will compare the plasma pharmacokinetics of a single 125mg oral dose of palbociclib in the presence and absence of rifampin-mediated enzyme induction in a fixed-sequence two-period study.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Palbociclib
* Drug: Rifampin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females of non-childbearing potential body mass index between 17.5-30.5 kg/m2 with a total body weight greater than 50kg Exclusion Criteria: Evidence or history of any clinically significant physiologic, psychological, or medical conditions a positive drug screen or alcohol breath test a baseline ECG demonstrating a QTc>450msecs or a QRS interval >120msecs

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-Arm Fixed-Sequence<br>Subjects will receive two different interventions in fixed-sequence two-period study. In the first period the subjects will receive a single-dose of palbociclib. In the second period, subjects will receive 12 days of rifampin and a single dose of palbociclib on day 8. In both periods, subjects will undergo pharmacokinetic sampling at prespecified time points up to 120 hours post palbociclib dose. | Drug: Palbociclib<br>* In period 1, patients will receive a single 125mg oral dose of palbociclib alone. Subjects will undergo palbociclib pharmacokinetic sampling at prespecified time points up to 120 hours post palbociclib dose. In period 2, subjects will receive 12 daily oral doses of 600mg of rifampin and a single 125mg oral dose of palbociclib on day 8. Subjects will undergo palbociclib pharmacokinetic sampling at prespecified time points up to 120 hours post palbociclib dose.<br>* Other names: palbociclib, PD-0332991;Drug: Rifampin<br>* In period 2, subjects will receive 12 daily oral doses of 600mg of rifampin and a single 125mg oral dose of palbociclib on day 8. Subjects will undergo palbociclib pharmacokinetic sampling at prespecified time points up to 120 hours post palbociclib dose.<br>* Other names: palbociclib, PD-0332991, rifampin, rifampicin;|

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). | 0-120 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0-120 hours post-dose | 

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) | 0-120 hours post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0-120 hours post-dose | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0-120 hours post-dose | 
| 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. | 0-120 hours post-dose | 
| 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. | 0-120 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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palbociclib, PD-0332991, rifampin, drug-drug interaction study