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Trial record 1 of 1 for:    NCT02222441
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Effect Of Modafinil And Pioglitazone On The Pharmacokinetics Of Palbociclib (PD-0332991)

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ClinicalTrials.gov Identifier: NCT02222441
Recruitment Status : Completed
First Posted : August 21, 2014
Last Update Posted : February 20, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Palbociclib alone Drug: Palbociclib plus Modafinil Drug: Palbociclib plus pioglitazone Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: 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
Study Start Date : October 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: Palbociclib (PD-0332991); Pioglitazone (Actos)




Primary Outcome Measures :
  1. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [ Time Frame: 0-120 hours ]
    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).

  2. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0-120 hours ]

Secondary Outcome Measures :
  1. Plasma Palbociclib Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0 to 120 hours ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  2. Plasma Palbociclib Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 to 120 hours ]
  3. Plasma Palbociclib Decay Half-Life (t1/2) [ Time Frame: 0 to 120 hours ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  4. Apparent Oral Clearance (CL/F) of Palbociclib [ Time Frame: 0 to 120 hours ]
    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.

  5. Apparent Volume of Distribution (Vz/F) of Palbociclib [ Time Frame: 0 to 120 hours ]
    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.

  6. Trough Plasma Concentrations of Modafinil, Modafinil sulfone, pioglitazone, hydroxy derivative of pioglitazone, and keto derivative of pioglitazone [ Time Frame: 0 to 120 hours ]
  7. Time of last quantifiable concentration for palbociclib [ Time Frame: 0 to 120 hours ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02222441


Locations
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United States, Connecticut
New Haven Clinical Research Unit
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02222441    
Other Study ID Numbers: A5481039
First Posted: August 21, 2014    Key Record Dates
Last Update Posted: February 20, 2015
Last Verified: February 2015
Keywords provided by Pfizer:
Palbociclib
Modafinil
Pioglitazone
Pharmacokinetics
Drug-Drug Interaction Study
Healthy Volunteers
CYP3A Inducers
Additional relevant MeSH terms:
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Pioglitazone
Palbociclib
Modafinil
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Wakefulness-Promoting Agents
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers