Study Of Three Different Stomach Acid Reducing Agents When Given With Palbociclib (PD-0332991) And Food

Study Overview
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Brief Summary
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To investigate the effect of acid reducing agents (an antacid and an H2-receptor antagonist and a proton pump inhibitor) on palbociclib bioavailability in the presence of food.

Official Title
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A Phase 1, Open-Label, 3-Period Crossover Study Of The Effect Of An Antacid, A Proton Pump Inhibitor And An H2-Receptor Antagonist On Palbociclib (PD-0332991) Bioavailability Under Fed Conditions In Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: palbociclib commercial free base
* Drug: famotidine
* Drug: rabeprazole
* Drug: palbociclib commercial free base
* Drug: antacid
* Drug: antacid


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 (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). 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 diseases (hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease). Use of tobacco or nicotine containing products within 3 months of screening. A positive urine drug screen.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Palbociclib under fed conditions<br> | Drug: palbociclib commercial free base<br>* 125 mg oral capsule single dose<br>Drug: famotidine<br>* 20 mg oral tablet 10 hours before and 2 hours after palbociclib<br>* Other names: Pepcid;Drug: rabeprazole<br>* 2 x 20 mg oral tablets daily for 6 days then on 7th day, 4 hours after palbociclib<br>* Other names: Aciphex;|
| Experimental: Cohort 2: Palbociclib under fed conditions<br> | Drug: palbociclib commercial free base<br>* 125 mg oral capsule single dose<br>Drug: antacid<br>* 30 mL orally once (2h before palbociclib)<br>* Other names: Mi-Acid Maximum Strength Liquid;Drug: antacid<br>* 30 mL orally once (2h after palbociclib)<br>* Other names: Mi-Acid Maximum Strength Liquid;|

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). | 6 days | 
| Maximum Observed Plasma Concentration (Cmax) |  | 6 days | 

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) | 6 days | 
| 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. | 6 days | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 6 days | 
| 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. | 6 days | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antacid, rabeprazole, famotidine, palbociclib, bioavailability