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

• 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)
• 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)

• 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.
  Interventions:

  • Drug: Palbociclib alone
  • Drug: Palbociclib plus Modafinil
• 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.
  Interventions:

  • Drug: Palbociclib alone
  • Drug: Palbociclib plus pioglitazone

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.