A Study to Estimate the Effect of CYP3A4 Inhibitors (Itraconazole, Diltiazem or Verapamil) on the Pharmacokinetics of Single Dose PF- 00489791 in Healthy Volunteers

• Drug: itraconazole
  itraconazole dosed at 200 mg
• Drug: diltiazem
  diltiazem dosed at 240 mg
• Drug: SR verapamil
  SR verapamil dosed at 240 mg
• Drug: PF-00489791
  PF-00489791 20 mg single dose administration

• Experimental: Treatment B
  Treatment B subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of itraconazole (200 mg once daily).
  Interventions:

  • Drug: itraconazole
  • Drug: PF-00489791
• Experimental: Treatment C
  Treatment C subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of diltiazem (240 mg once daily).
  Interventions:

  • Drug: diltiazem
  • Drug: PF-00489791
• Experimental: Treatment D
  Treatment D subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of verapamil (240 mg once daily).
  Interventions:

  • Drug: SR verapamil
  • Drug: PF-00489791

Inclusion Criteria:

• Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests) with a Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs.) and with a personally signed and dated informed consent document and who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Participating female subjects of non-childbearing potential must meet at least one of the following criteria: achieved postmenopausal status; have undergone a documented hysterectomy and/or bilateral oophorectomy; have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.

Exclusion Criteria:

• Subjects cannot be included in the study if there is: the presence/ history of any disorder that prevents study completion
• Evidence/history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
• Any surgical or medical condition that may interfere with the absorption distribution, metabolism, or excretion of the study drug
• A positive urine drug screen or history of regular excessive alcohol consumption or use of tobacco-or nicotine-containing products in excess or from 24-hours prior to admission until discharge
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 halflives preceding the first dose of study med.
• Out of range blood pressure including current evidence of orthostatic change in blood pressure
• Abnormal ECG or history or current evidence of clinically important cardiac conduction abnormalities.
• Also excluded are: pregnant or breastfeeding female subjects; male subjects with partners currently pregnant; male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as described in the protocol for the duration of the study and for at least 28 days after the last dose of investigational product.