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

NCT02222441 | Completed Phase 1

• 1 other identifier: A5481039
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Palbociclib; Modafinil; Pioglitazone; Pharmacokinetics; Drug-Drug Interaction Study; Healthy Volunteers; CYP3A Inducers

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Plasma Palbociclib Area Under the Curve From Time Zero to Last Quantifiable 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)

  0 to 120 hours

• Apparent Oral Clearance (CL/F) of Palbociclib

  0 to 120 hours

• Apparent Volume of Distribution (Vz/F) of Palbociclib

  0 to 120 hours

Study Arms (2)

Fixed sequence modafinil DDI arm (Cohort 1)

EXPERIMENTAL

Fixed sequence study with treatment A of palbociclib alone, followed by treatment B of palbociclib with modafinil in Cohort 1.

Drug: Palbociclib alone; Drug: Palbociclib plus Modafinil

Fixed sequence pioglitazone DDI arm (Cohort 2)

EXPERIMENTAL

For Cohort 2, fixed sequence study with treatment A of palbociclib alone, followed by treatment C of palbociclib with pioglitazone.

Drug: Palbociclib alone; Drug: Palbociclib plus pioglitazone

Interventions

Palbociclib alone DRUG

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.

Also known as: Palbociclib, PD-0332991

Fixed sequence modafinil DDI arm (Cohort 1)

Palbociclib plus Modafinil DRUG

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.

Also known as: Palbociclib (PD-0332991); Modafinil (Provigil)

Fixed sequence modafinil DDI arm (Cohort 1)

Palbociclib plus pioglitazone DRUG

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.

Also known as: Palbociclib (PD-0332991); Pioglitazone (Actos)

Fixed sequence pioglitazone DDI arm (Cohort 2)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

palbociclib; Modafinil; Pioglitazone

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 21, 2014
• Study Start: October 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 20, 2015

Record last verified: 2015-02

Locations

US (1)