A Study To Investigate The Drug-Drug Interaction Potential Of Rifampin OnThe Investigational Agent Palbociclib (PD-0332991)

• ClinicalTrials.gov Identifier: NCT01953731
• Recruitment Status: Completed
• First Posted: October 1, 2013
• Last Update Posted: January 20, 2014
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 26, 2013
• First Posted Date: October 1, 2013
• Last Update Posted Date: January 20, 2014
• Study Start Date: October 2013
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2013)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [ Time Frame: 0-120 hours post-dose ]
  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).
• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0-120 hours post-dose ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 26, 2013)

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0-120 hours post-dose ]
  Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0-120 hours post-dose ]
• Plasma Decay Half-Life (t1/2) [ Time Frame: 0-120 hours post-dose ]
  Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
• Apparent Oral Clearance (CL/F) [ Time Frame: 0-120 hours post-dose ]
  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.
• Apparent Volume of Distribution (Vz/F) [ Time Frame: 0-120 hours post-dose ]
  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.

• 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 Study To Investigate The Drug-Drug Interaction Potential Of Rifampin OnThe Investigational Agent Palbociclib (PD-0332991)
• Official Title: A Phase 1, Open-Label Fixed-Sequence 2-Period Study To Investigate The Effect Of Multiple Doses Of Rifampin On Palbociclib (PD-0332991) Pharmacokinetics In Healthy Volunteers
• Brief Summary: This study will compare the plasma pharmacokinetics of a single 125mg oral dose of palbociclib in the presence and absence of rifampin-mediated enzyme induction in a fixed-sequence two-period study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Healthy

Intervention

• Drug: Palbociclib

  In period 1, patients will receive a single 125mg oral dose of palbociclib alone. Subjects will undergo palbociclib pharmacokinetic sampling at prespecified time points up to 120 hours post palbociclib dose.

  In period 2, subjects will receive 12 daily oral doses of 600mg of rifampin and a single 125mg oral dose of palbociclib on day 8. Subjects will undergo palbociclib pharmacokinetic sampling at prespecified time points up to 120 hours post palbociclib dose.

  Other Name: palbociclib, PD-0332991
• Drug: Rifampin
  In period 2, subjects will receive 12 daily oral doses of 600mg of rifampin and a single 125mg oral dose of palbociclib on day 8. Subjects will undergo palbociclib pharmacokinetic sampling at prespecified time points up to 120 hours post palbociclib dose.
  Other Name: palbociclib, PD-0332991, rifampin, rifampicin

Study Arms

Experimental: Single-Arm Fixed-Sequence

Subjects will receive two different interventions in fixed-sequence two-period study. In the first period the subjects will receive a single-dose of palbociclib. In the second period, subjects will receive 12 days of rifampin and a single dose of palbociclib on day 8. In both periods, subjects will undergo pharmacokinetic sampling at prespecified time points up to 120 hours post palbociclib dose.

Interventions:

• Drug: Palbociclib
• Drug: Rifampin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 16, 2014): 15
• Original Estimated Enrollment (submitted: September 26, 2013): 14
• Actual Study Completion Date: January 2014
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy males or females of non-childbearing potential
• body mass index between 17.5-30.5 kg/m2 with a total body weight greater than 50kg

Exclusion Criteria:

• Evidence or history of any clinically significant physiologic, psychological, or medical conditions
• a positive drug screen or alcohol breath test
• a baseline ECG demonstrating a QTc>450msecs or a QRS interval >120msecs

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: NCT01953731
• Other Study ID Numbers: A5481017
• 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: January 2014