A Study to Estimate the Effect of CYP3A4 Inhibitors (Itraconazole, Diltiazem or Verapamil) on the Pharmacokinetics of Single Dose PF- 00489791 in Healthy Volunteers
Condition: Healthy Volunteers
Intervention: itraconazole; diltiazem; SR verapamil; PF-00489791
Intervention description: itraconazole dosed at 200 mg; diltiazem dosed at 240 mg; SR verapamil dosed at 240 mg; PF-00489791 20 mg single dose administration
Intervention MeSH terms: Itraconazole; Verapamil; Diltiazem
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of the study is to estimate the effects of different strong enzyme
      (CYP3A4) inhibitors, itraconazole, diltiazem, or verapamil on the single dose
      pharmacokinetics of PF-00489791 in healthy volunteers. The study will enroll approximately 18
      subjects that are randomized to 1 of 3 treatment groups. The study is also intended to
      determine the safety and tolerability of single-dose PF- 00489791 when it is administered
      with steady-state itraconazole, diltiazem, or verapamil.
    

Eligibility criteria:

        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.