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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Palbociclib alone; Drug: Palbociclib + Rabeprazole

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fixed sequence crossover; All the subjects will undergo the treatment of Palbociclib alone first and then treatment of Palbociclib and Rabeprazole.

Drug: Palbociclib alone; 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.; Other Names: Period 1; Drug: Palbociclib + Rabeprazole; 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.; Other Names: Period 2

What is the study measuring?

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

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: September 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: August 5, 2013
• First Submitted That Met QC Criteria: August 5, 2013
• First Posted (Estimate): August 7, 2013

Study Record Updates

• Last Update Posted (Estimate): October 8, 2015
• Last Update Submitted That Met QC Criteria: October 6, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Volunteers; Rabeprazole; Palbociclib; PD-0332991; Proton Pump Inhibitor; DDI
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Protein Kinase Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Palbociclib; Rabeprazole
• Other Study ID Numbers: A5481018