Drug Interaction Study To Investigate The Potential Effect Of Proton Pump Inhibitor On The Pharmacokinetics Of Palbociclib (PD-0332991)

Study Overview
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Brief Summary
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Fixed sequence, 2-period crossover study to compare the pharmacokinetic profiles of Palbociclib in absence and presence of prior administration of proton pump inhibitor Rabeprazole. The increased gastric pH achieved by the treatment with multiple doses of Rabeprazole might affect the absorption process of Palbociclib.

Official Title
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A Phase 1, Open-Label Fixed-Sequence 2-Period Crossover Study Of Palbociclib In Healthy Subjects To Investigate The Potential Effect Of Antacid Treatment On The Pharmacokinetics Of A Single Oral Dose Administered Under Fasted Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Palbociclib alone
* Drug: Palbociclib + Rabeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects of non-childbearing potential; Healthy subjects identified by a detailed medical history, full physical examination including blood pressure and pulse rate measurement, 12-lead ECG or clinical laboratory test. Exclusion Criteria: A positive urine drug screen, urine cotinine test or alcohol breath test. Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study medication. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives prior to the first dose of study medication. All antacid agents must be discontinued 28 days prior to the first dose of study medication.

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 |
| --- | --- |
| Experimental: Fixed sequence crossover<br>All the subjects will undergo the treatment of Palbociclib alone first and then treatment of Palbociclib and Rabeprazole. | Drug: Palbociclib alone<br>* Single dose of 125mg Palbociclib capsule will be administered to subjects orally and then PK samples will be collected at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours.<br>* Other names: Period 1;Drug: Palbociclib + Rabeprazole<br>* Two Rabeprazole 20mg tablets will be given to subjects orally once daily for 7 days. Then on the same day at least 4 hours after the last dose of Rabeprazole, single dose of 125mg Palbociclib capsule will be given to subjects orally then followed by PK samplings at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours.<br>* Other names: Period 2;|

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) | 0-120 hours | 
| Area Under the Curve from Time Zero to 72 hours | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hours | 0-72 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. | 0-120 hours | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0-120 hours | 
| Time For the Last Quantifiable Concentration (Tlast) |  | 0-120 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. | 0-120 hours | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0-120 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palbociclib, PD-0332991, Proton Pump Inhibitor, DDI, Healthy Volunteers, Pharmacokinetics, Rabeprazole