1. Healthy female subjects of non childbearing potential and/or male subjects, between
the ages of 18 and 55 years
2. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
3. Personally signed and dated Informed Consent
4. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures.
1. Clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal,
cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
2. Any condition possibly affecting drug absorption
3. Positive urine drug screen.
4. Heavy smokers
5. History of regular heavy alcohol consumption within 6 months of Screening.
6. Treatment with an investigational drug within 30 days (or as determined by the local
requirement) or 5 half lives
7. Screening supine blood pressure
or>=140 mm Hg (systolic) or >=90 mm Hg (diastolic), following at least 5 minutes of
8. Screening pulse (HR) >100 bpm after at least 5 minutes of rest.
9. Single supine 12 lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at
10. Abnormal chest X ray
11. History of TB or active or latent or inadequately treated infection, positive
Quantiferon TB test.
12. History of hepatitis or positive testing for human HIV,HepBsAg, HepBc Ab or HCVAb
13. Any medical history of disease [ie, Gilbert's disease] that has the potential to cause
a rise in total bilirubin over the ULN
14. Clinical laboratory abnormalities including:
- Creatine kinase >1.2 X ULN;
- CK MB > ULN;
- Serum myoglobin >1.2 X ULN;
- Cardiac Troponin I (cTn I) > ULN of the laboratory reference range;
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) >=2 x ULN, total
serum bilirubin >=1.5 mg/dL;
- Subjects with benign ethnic neutropenia;
15. Nursing female subjects; male subjects with partners currently pregnant; male subjects
able to father children 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 28
days after the last dose of investigational product or longer based upon the
compound's half life characteristics.
16. 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 investigational product
until discharge from the study at the end of Period 2.
Herbal supplements and hormone replacement therapy must be discontinued 28 days prior
to the first dose of investigational product. Acetaminophen/paracetamol should not be
used. As an exception, ibuprofen may be used at doses of 200 to 400 mg orally every 6
hours as needed for up to 3 of 7 consecutive days.
17. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more
within 56 days prior to dosing.
18. History of sensitivity to heparin or heparin induced thrombocytopenia.
19. History of cancer (other than treated basal cell and squamous cell carcinoma of the
skin) in the previous 5 years.
20. Previous exposure to PF 06650833.
21. Unwilling or unable to comply with the Lifestyle guidelines
22. Subjects who are investigational site staff members directly involved in the conduct
of the study and their family members, site staff members otherwise supervised by the
Investigator, or subjects who are Pfizer employees directly involved in the conduct of
23. Other severe acute or chronic medical or psychiatric condition or laboratory