A Pilot Study To Investigate The Effect Of Concurrent Antacid Administration On The Bioavailability Of Six Experimental Formulations Of Palbociclib

A Phase 1, Open-Label Fixed-Sequence 2-Period Crossover Study Of Palbociclib (pd-0332991) In Healthy Volunteers To Estimate The Effect Of Antacid Treatment On The Bioavailability Of A 125 Mg Single Dose Of Six Experimental Formulations Of Palbociclib Relative To Palbociclib Administration Alone Under Fasted Conditions

This study will investigate whether concurrent administration of rabeprazole, an antacid known as a proton pump inhibitor, alters the absorption of the drug palbociclib when given as one of six experimental formulations.

Study Overview

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

Detailed Description

This will be a 6 cohort study investigating one experimental formulation of palbociclib in each of the six cohorts of 10 healthy subjects. Each cohort will receive two treatments in a fixed-sequence. In Period 1, all subjects will receive a single 125mg dose of palbociclib alone and undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose. In Period 2, all subjects will receive daily 40mg doses of Rabeprazole for 7 consecutive days, and approximately 4 hours after the Day 7 rabeprazole dose each subject will receive a single 125mg dose of palbociclib. Subjects will undergo serial pharmacokinetic blood sampling up to 120 hours post-dose.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143
      • MRA Clinical Research - Phase 1
    • South Miami, Florida, United States, 33143
      • Miami Research Associates, LLC
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Male or Female of non-childbearing potential,
• Having a body weight >50 kg
• Having a bopy mass index (BMI) between 17.5 and 30.5 kg/m2.

Exclusion Criteria:

• Any condition possibly affecting drug absorption (eg, gastrectomy)
• A positive urine drug or cotinine test
• A known history of hypersensitivity to palbociclib
• A supine systolic blood pressure >140 mmHg, or a QTc >450 msec.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Cohort 1 will receive a 125 mg round yellow palbociclib tablet containing succinic acid	Drug: Palbociclib Alone; In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991; Drug: Palbociclib + Rabeprazole; In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI
Experimental: Cohort 2; Cohort 2 will receive a 125 mg oval yellow palbociclib spray-dried dispersion tablet containing HMPC E3	Drug: Palbociclib Alone; In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991; Drug: Palbociclib + Rabeprazole; In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI
Experimental: Cohort 3; Cohort 3 will receive a 125 mg oval yellow palbociclib spray-dried dispersion tablet with HMPC E3 and succinic acid.	Drug: Palbociclib Alone; In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991; Drug: Palbociclib + Rabeprazole; In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI
Experimental: Cohort 4; Cohort 4 will receive a 125 mg oval white/yellow palbociclib bilayer tablet with tartaric and succinic acid.	Drug: Palbociclib Alone; In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991; Drug: Palbociclib + Rabeprazole; In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI
Experimental: Cohort 5; Cohort 5 will receive a 125 mg oval yellow palbociclib fluid bed granulation tablet with succinic acid.	Drug: Palbociclib Alone; In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991; Drug: Palbociclib + Rabeprazole; In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI
Experimental: Cohort 6; Cohort 6 will receive a 125 mg palbociclib oral solution	Drug: Palbociclib Alone; In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991; Drug: Palbociclib + Rabeprazole; In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.; Other Names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCinf	Area under the concentration-time curve from time zero to infinity.	Pre-dose to 120 hours post-dose
Cmax	Maximum observed plasma concentration	Pre-dose to 120 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast	Area under the concentration-time curve from time zero to the time of the last quantifiable concentration.	Pre-dose to 120 hours post-dose
CL/F	Apparent oral clearance from plasma	Pre-dose to 120 hours post-dose
Tmax	Time of the maximum observed concentration post-dose.	Pre-dose to 120 hours post-dose
Vz/F	Apparent volume of distribution	Pre-dose to 120 hours post-dose
t1/2	Terminal phase half-life	Pre-dose to 120 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: December 4, 2014
• First Submitted That Met QC Criteria: December 8, 2014
• First Posted (Estimate): December 9, 2014

Study Record Updates

• Last Update Posted (Estimate): May 28, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Palbociclib, Rabeprazole, Proton Pump Inhibitor, Drug Interaction Study, DDI
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Protein Kinase Inhibitors; Anti-Ulcer Agents; Palbociclib; Rabeprazole; Proton Pump Inhibitors
• Other Study ID Numbers: A5481041