A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PF-06842874 in Healthy Participants

This study will be the first time PF-06842874 is administered to humans. The purpose of Part A of the study is to investigate the safety, tolerability, and pharmacokinetics of PF-06842874 following administration of single oral doses as an immediate-release or modified-release formulation to healthy adult participants. Part B of this study will evaluate the relative bioavailability of a modified-release formulation of PF-06842874 for its potential use in future clinical studies. The effect of food on PF-06842874 pharmacokinetics may also be evaluated in this study.


Eligibility Criteria:
Inclusion Criteria:

* Female participants of non-childbearing potential and male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, clinical laboratory tests, and cardiac monitoring.
* Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
* Capable of giving signed informed consent.

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
* Any condition possibly affecting drug absorption.
* History of human immunodeficiency virus infection (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody.
* Participants with benign ethnic neutropenia or cyclic neutropenia.
* Other acute or chronic medical or psychiatric condition.
* Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product.
* Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer).
* A positive urine drug test.
* Screening supine blood pressure (BP) ≥140 mmHg (systolic) or ≥90 mmHg (diastolic), following at least 5 minutes of supine rest.
* Baseline 12-lead standard electrocardiogram (ECG) that demonstrates clinically relevant abnormalities.
* Participants with ANY of the following abnormalities in clinical laboratory tests at screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.25× upper limit of normal (ULN); total bilirubin level ≥1.5× ULN; participants 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; hemoglobin ≤14 gm/dL (males) and ≤13 gm/dL (females); neutrophils \<1500 cells/mm3.
* History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of screening.
* Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
* History of sensitivity to heparin or heparin-induced thrombocytopenia.
* Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.