Effect Of Modafinil And Pioglitazone On The Pharmacokinetics Of Palbociclib (PD-0332991)

A Phase 1, Open-label, Fixed-sequence, 2-cohort, 2-period Study To Investigate The Effect Of Modafinil And Pioglitazone Given As Multiple Doses On Single Dose Pharmacokinetics Of Palbociclib (Pd-0332991) In Healthy Volunteers

This study is designed to evaluate the potential effect of the moderate CYP3A inducer modafinil and the weak CYP3A inducer pioglitazone on the pharmacokinetics of palbociclib.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Palbociclib alone; Drug: Palbociclib plus Modafinil; Drug: Palbociclib plus pioglitazone

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

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:

• Healthy male and/or female subjects of non childbearing potential between the ages of 18 and 55 years, inclusive.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• Subjects with a self-reported history of addiction, especially to stimulants.
• A positive urine drug screen or alcohol breath test.
• Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential; male subjects with partners currently pregnant; male subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 90 days after the last dose of investigational product.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fixed sequence modafinil DDI arm (Cohort 1); Fixed sequence study with treatment A of palbociclib alone, followed by treatment B of palbociclib with modafinil in Cohort 1.	Drug: Palbociclib alone; A single 125 mg dose of palbociclib free base capsule given orally alone in the fed state, followed by 120 hours of PK sample collection.; Other Names: Palbociclib, PD-0332991; Drug: Palbociclib plus Modafinil; For Cohort 1, modafinil 200 mg once daily for 7 days, followed by 400 mg once daily for 25 days; on Day 28, a single oral 125 mg dose of palbociclib will be given with modafinil after a meal, followed by 120 hours of PK sample collection.; Other Names: Palbociclib (PD-0332991); Modafinil (Provigil)
Experimental: Fixed sequence pioglitazone DDI arm (Cohort 2); For Cohort 2, fixed sequence study with treatment A of palbociclib alone, followed by treatment C of palbociclib with pioglitazone.	Drug: Palbociclib alone; A single 125 mg dose of palbociclib free base capsule given orally alone in the fed state, followed by 120 hours of PK sample collection.; Other Names: Palbociclib, PD-0332991; Drug: Palbociclib plus pioglitazone; For Cohort 2, pioglitazone 45 mg once daily for a total of 19 days; On Day 15, a single oral 125 mg dose of palbociclib will be given with pioglitazone after a meal, followed by 120 hours of PK sample collection.; Other Names: Palbociclib (PD-0332991); Pioglitazone (Actos)

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
Plasma Palbociclib Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0 to 120 hours
Plasma Palbociclib Time to Reach Maximum Observed Plasma Concentration (Tmax)		0 to 120 hours
Plasma Palbociclib Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0 to 120 hours
Apparent Oral Clearance (CL/F) of Palbociclib	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 to 120 hours
Apparent Volume of Distribution (Vz/F) of Palbociclib	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 to 120 hours
Trough Plasma Concentrations of Modafinil, Modafinil sulfone, pioglitazone, hydroxy derivative of pioglitazone, and keto derivative of pioglitazone		0 to 120 hours
Time of last quantifiable concentration for palbociclib		0 to 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: October 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 19, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (Estimate): August 21, 2014

Study Record Updates

• Last Update Posted (Estimate): February 20, 2015
• Last Update Submitted That Met QC Criteria: February 18, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Volunteers; Modafinil; Palbociclib; Pioglitazone; Drug-Drug Interaction Study; CYP3A Inducers
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Palbociclib; Pioglitazone; Modafinil
• Other Study ID Numbers: A5481039