A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Repeat Doses of PF-06372865 in Healthy Subjects

• Drug: Placebo
  Placebo
• Drug: PF-06372865
  PF-06372865

• Placebo Comparator: Placebo
  Subjects receiving placebo
  Intervention: Drug: Placebo
• Experimental: PF-06372865
  Subjects receiving PF-06372865
  Intervention: Drug: PF-06372865

Inclusion Criteria:

1. Healthy female subjects of non-childbearing potential and/or male subjects between the ages of 18 and 55 years
2. Body mass index of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)
3. Subjects who are willing and able to comply with all study procedures (including being able to swallow up to 8 tablets/dose or 16 tablets/day)
4. For optional Japanese subjects only: Japanese subjects currently residing in the United States who have 4 biologic Japanese grandparents born in Japan

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
2. Subjects with history of sleep apnea
3. Any condition possibly affecting drug absorption (eg, gastrectomy)
4. Positive urine drug test
5. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males
6. Treatment with an investigational drug within 30 days or 5 half-lives of the first dose of PF-06372865 (whichever is longer)
7. Clinically significant orthostatic hypotension at screening or screening supine BP >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), following at least 5 minutes of supine rest
8. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS interval >120 msec
9. Subjects with any of the following abnormalities in clinical laboratory tests at screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >=1.5x upper limit of normal (ULN); total bilirubin level >=1.5x ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is <=ULN
10. Fertile male subjects who are unwilling or unable to use a highly effective method of contraception for the duration of the study and for at least 60 days after the last dose of PF-06372865
11. Male subjects whose partners are currently pregnant
12. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of PF-06372865
13. Use of herbal supplements or hormone replacement therapy within 28 days prior to the first dose of PF-06372865
14. Blood donation of approximately 1 pint (500 mL) or more within 60 days prior to dosing
15. History of sensitivity to heparin or heparin-induced thrombocytopenia
16. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody
17. Other acute or chronic medical or psychiatric condition including recent or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or PF-06372865 administration or may interfere with the interpretation of study results
18. Subjects with active suicidal ideations or suicidal behavior within 5 years prior to screening
19. Subjects with history of cyclic neutropenia.
20. Subjects with known history of hypersensitivity to benzodiazepines, or for whom benzodiazepines would be contraindicated
21. Subjects who have previously been exposed to, or participated in a study with, PF-06372865
22. Subjects with folate deficiency
23. Subjects who have had an X-ray within 4 weeks prior to screening