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

• ClinicalTrials.gov Identifier: NCT02311946
• Recruitment Status: Completed
• First Posted: December 9, 2014
• Last Update Posted: May 28, 2015
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: December 4, 2014
• First Posted Date: December 9, 2014
• Last Update Posted Date: May 28, 2015
• Study Start Date: January 2015
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 8, 2014)

• AUCinf [ Time Frame: Pre-dose to 120 hours post-dose ]
  Area under the concentration-time curve from time zero to infinity.
• Cmax [ Time Frame: Pre-dose to 120 hours post-dose ]
  Maximum observed plasma concentration

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 8, 2014)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Pilot Study To Investigate The Effect Of Concurrent Antacid Administration On The Bioavailability Of Six Experimental Formulations Of Palbociclib
• Official Title: 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
• Brief Summary: 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.
• 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
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Healthy

Intervention

• 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 Name: 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 Name: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI

Study Arms

• Experimental: Cohort 1
  Cohort 1 will receive a 125 mg round yellow palbociclib tablet containing succinic acid
  Interventions:

  • Drug: Palbociclib Alone
  • Drug: Palbociclib + Rabeprazole
• Experimental: Cohort 2
  Cohort 2 will receive a 125 mg oval yellow palbociclib spray-dried dispersion tablet containing HMPC E3
  Interventions:

  • Drug: Palbociclib Alone
  • Drug: Palbociclib + Rabeprazole
• Experimental: Cohort 3
  Cohort 3 will receive a 125 mg oval yellow palbociclib spray-dried dispersion tablet with HMPC E3 and succinic acid.
  Interventions:

  • Drug: Palbociclib Alone
  • Drug: Palbociclib + Rabeprazole
• Experimental: Cohort 4
  Cohort 4 will receive a 125 mg oval white/yellow palbociclib bilayer tablet with tartaric and succinic acid.
  Interventions:

  • Drug: Palbociclib Alone
  • Drug: Palbociclib + Rabeprazole
• Experimental: Cohort 5
  Cohort 5 will receive a 125 mg oval yellow palbociclib fluid bed granulation tablet with succinic acid.
  Interventions:

  • Drug: Palbociclib Alone
  • Drug: Palbociclib + Rabeprazole
• Experimental: Cohort 6
  Cohort 6 will receive a 125 mg palbociclib oral solution
  Interventions:

  • Drug: Palbociclib Alone
  • Drug: Palbociclib + Rabeprazole

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 8, 2014): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02311946
• Other Study ID Numbers: A5481041
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: May 2015