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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01953731

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Palbociclib Drug: Rifampin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

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

Study Start Date :

Oct 1, 2013

Actual Primary Completion Date :

Jan 1, 2014

Actual Study Completion Date :

Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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.	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 Names: 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 Names: palbociclib, PD-0332991, rifampin, rifampicin

Arm

Intervention/Treatment

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.

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 Names:

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 Names:

palbociclib, PD-0332991, rifampin, rifampicin

Outcome Measures

Primary Outcome Measures

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [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) [0-120 hours post-dose]

Secondary Outcome Measures

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [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) [0-120 hours post-dose]
Plasma Decay Half-Life (t1/2) [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) [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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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