A Study In Healthy Volunteers To Estimate The Effect Of The Active Ingredient Particle Size And Percentage Of The Excipients Used To Formulate The Capsules In The Dissolution Rate Of The Formulations In The Gastrointestinal Tract

Study Overview
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Brief Summary
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The particle size of the active ingredient may impact dissolution rate in the gastro intestinal tract and hence the amount of drug available for absorption. Similarly, differences in the percentage of the excipients used in the formulated capsules may affect dissolution rate. The purpose of this study is to estimate the effect that particle size and percentage of excipients could have in drug absorption, which will improve the manufacturing process of the formulated capsules.

Official Title
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A Phase 1, Open-Label 4 Sequence 4 Period Crossover Study In Healthy Volunteers To Estimate The Effect Of Active Pharmaceutical Ingredient Particle Size And Lubrication On The Bioavailability Of A Single 125 Mg Dose Of Palbociclib (PD-0332991) Administered Under Fasted Conditions

Conditions
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Healthy

Intervention / Treatment
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* Other: Palbociclib Formulation Reference
* Other: Palbociclib Formulation Test
* Other: Palbociclib Formulation Test
* Other: Palbociclib Formulation Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects and/or female subjects with no physical possibility of getting pregnant. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) 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 disease. Any condition possibly affecting drug absorption (eg, gastrectomy). A positive urine drug screen. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening. Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) preceding the first dose of study medication. Pregnant females; breastfeeding females; females with physical possibility of getting pregnant .

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment A<br>treatment A, reference, 20 micron palbociclib and lubrication level 1 | Other: Palbociclib Formulation Reference<br>* Single 45 mg dose; Dosage form is capsule taken orally.<br>|
| Active Comparator: Treatment B<br>treatment B, test, 50 micron palbociclib and lubrication level 1 | Other: Palbociclib Formulation Test<br>* Single 45 mg dose; Dosage form is capsule taken orally.<br>|
| Active Comparator: Treatment C<br>treatment C, test, 20 micron palbociclib and lubrication level 2 | Other: Palbociclib Formulation Test<br>* Single 45 mg dose; Dosage form is capsule taken orally.<br>|
| Active Comparator: Treatment D<br>treatment D, test, 20 micron palbociclib and lubrication level 3 | Other: Palbociclib Formulation Test<br>* Single 45 mg dose; Dosage form is capsule taken orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Concentration-Time Curve (AUC) from time zero extrapolate to infinite time | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. | 7 days | 
| 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) | 7 days | 
| Maximum Observed Plasma Concentration (Cmax) |  | 2 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) | 7 days | 
| Area under the Concentration-Time Curve (AUC) from 0 to 72 | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. | 3 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. | 7 days | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 2 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. | 7 days | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 7 days |