Relative Bioavailability For Palbociclib Formulations

A Phase 1, Open-Label, 6 Sequence, 3 Period, Crossover Study Of Palbociclib (PD-0332991) In Healthy Volunteers To Estimate The Relative Bioavailability Of 3 Palbociclib Formulations

This study is to assess the relative bioavailability of palbociclib hard gelatin capsule formulation (API 41 micrometer and dissolution Level 1) and palbociclib hard gelatin capsule formulation (API 16 micrometer and dissolution Level 2) compared to the palbociclib hard gelatin capsule formulation (API 16 micrometer and dissolution Level 1) after single 125 mg oral doses under fed conditions in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Palbociclib Formulation Reference; Drug: Palbociclib Formulation Test; Drug: Palbociclib Formulation Test

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment A (Reference)	Drug: Palbociclib Formulation Reference; 125 mg single dose of palbociclib formulation with 16 micrometer API particle size and dissolution level 1, which is representative of the intended commercial hard gelatin capsule.
Other: Treatment B (Test)	Drug: Palbociclib Formulation Test; 125 mg single dose of palbociclib formulation with 41 micrometer API particle size and dissolution level 1; Drug: Palbociclib Formulation Test; 125 mg single dose of palbociclib formulation with 16 micrometer API particle size and dissolution level 2
Other: Treatment C (Test)	Drug: Palbociclib Formulation Test; 125 mg single dose of palbociclib formulation with 41 micrometer API particle size and dissolution level 1; Drug: Palbociclib Formulation Test; 125 mg single dose of palbociclib formulation with 16 micrometer API particle size and dissolution level 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)		6 days
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

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)		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.	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: March 7, 2014
• First Submitted That Met QC Criteria: March 7, 2014
• First Posted (Estimate): March 11, 2014

Study Record Updates

• Last Update Posted (Estimate): June 4, 2014
• Last Update Submitted That Met QC Criteria: June 2, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: healthy volunteer; bioavailability; formulation; palbociclib
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: A5481040