A Phase 1, Randomized, Double Blind, Placebo Controlled, Multiple Dose, 2 Way Crossover Study To Evaluate The Safety And Pharmacodynamic Effects Of Pf 06282999 Using An Endotoxin (Lipopolysaccharide) Induced Inflammatory Response Model In Healthy Adult Subjects

Peak Myeloperoxidase (MPO) Activity Following Inflammatory Stimulus

时间窗: Days 1, 3-5

MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.

MPO Activity (Area Under the Concentration-time Profile From 0.5 to 2 Hours [AUC0.5-2hrs]) Following Inflammatory Stimulus

时间窗: Days 1, 3-5

MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.

MPO Activity (Area Under the Concentration-time Profile From 0 to 2 Hours [AUC0-2hrs]) Following Inflammatory Stimulus

时间窗: Days 1, 3-5

MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.

Number of Participants With Laboratory Test Abnormalities

时间窗: Baseline up to 7-10 days following the last dose of PF-06282999/Placebo in Period 2

Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy). Due to early termination of the study, only laboratory data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs

时间窗: From Day 0 till approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2 (up to approximately 2 months)

An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as newly occurring AEs or those worsening after first dose. Due to early termination of the study, only AE data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.

Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria

时间窗: Screening and Days 1-2, 4-5, and approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2 for orthostatic (orth) measurements; Day 3 for supine measurements

Categorical summarization criteria in vital signs included: sitting, supine, and standing systolic blood pressure (SBP) of less than (\<)90 millimeters of mercury (mm Hg) or change (increase \[inc\] or decrease \[dec\]) in sitting, supine and standing SBP of more than or equal to (\>=)30 mm Hg; supine, sitting, and standing diastolic blood pressure (DBP) of \<50 mm Hg or change (inc or dec) in sitting, supine, and standing DBP of \>=20 mm Hg; supine and sitting pulse rate (PR) of \<40 or more than (\>)120 beats per minute (bpm); and standing PR of \<40 or \>140 bpm. Due to early termination of the study, only vital signs data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.

Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria

时间窗: Screening; Days 1-5 and approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2

Criteria for ECG (12-lead) values meeting categorical summarization criteria were: the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval \>=300 milliseconds (msec) and increase from baseline \>=25/50%; time from the beginning of the ECG Q wave to the end of the S wave corresponding to ventricular depolarization (QRS) interval \>=140 msec and increase of \>=50%; the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval \>=500 msec; QT corrected using the Fridericia formula (QTcF) of 450 to \<480 msec, 480 to \<500 msec, and \>=500 msec, or an increase of 30 to \<60 msec or \>=60 msec. Due to early termination of the study, only ECG data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.

Number of Participants With Abnormal Urinary Biomarker Values

时间窗: Days 1-3 prior to dosing with PF-06282999/Placebo; and Days 4-5

Urinary biomarkers included albumin, neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin-C.