A Study To Evaluate The Safety And Effects On The Body Of... | NCT01965600

ID	Type	Description	Link
2013-001528-20	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Cohort 1	Experimental		Drug: PF-06282999 Drug: Placebo Other: LPS
Cohort 2	Experimental		Drug: PF-06282999 Drug: Placebo Other: LPS

Name	Type	Description	Arm Group Labels	Other Names
PF-06282999	Drug	Tablet, 125 mg, TID, 3 days, 1 of 2 periods	Cohort 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Peak Myeloperoxidase (MPO) Activity Following Inflammatory Stimulus	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.	Days 1, 3-5
MPO Activity (Area Under the Concentration-time Profile From 0.5 to 2 Hours [AUC0.5-2hrs]) Following Inflammatory Stimulus	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.	Days 1, 3-5
MPO Activity (Area Under the Concentration-time Profile From 0 to 2 Hours [AUC0-2hrs]) Following Inflammatory Stimulus	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.	Days 1, 3-5
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs	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.

Secondary Outcomes

Measure	Description	Time Frame
Concentrations of TNF-alpha, IL-1 Beta, IL-6, IL-8, and hsCRP	The effect of multiple oral doses of PF-06282999 on inflammatory biomarkers was a secondary objective in this study. The biomarkers are tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and high-sensitivity C-reactive protein (hsCRP).	Days 1, 3, and 4

Eligibility Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
(Drug Shipment Address ONLY) Duke University Health Systems (DUHS) Investigational Drug Services		Durham	North Carolina	27710	United States

Label	URL
To obtain contact information for a study center near you, click here.	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	PF-06282999 125 mg TID Followed by Placebo	Participants received PF-06282999 125 milligrams (mg) three times daily (TID) orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm). On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3. After about 15 days of washout, participants returned for the second period where they received placebo in the same manner as active treatment before.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	All Participants	Participants received PF-06282999 125 mg TID or 500 mg BID or matching placebo orally in tablet form from Days 1 to 3. On Day 3, participants received a dose of LPS as an IV bolus at a dose of 4 ng/kg over 45-60 secs 2 hours after the morning dose of PF-06282999 or matching placebo. A final dose of PF-06282999 or matching placebo was administered on the evening of Day 3. Period 2 started after a washout period of approximately 15 days with at least 21 days in between administration of LPS. Participants who took active treatment (PF-06282999) in Period 1 received placebo in Period 2 and vice versa.

Units	Counts
Participants	BG00023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Peak Myeloperoxidase (MPO) Activity Following Inflammatory Stimulus

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.

Due to early termination of the study, there was not enough participants to perform meaningful analysis on this endpoint. As such, no analysis was done.

Posted

Days 1, 3-5

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.
OG002	PF-06282999 500 mg BID	All participants who received PF-06282999 500 mg BID orally in tablet form from Days 1 to 3 (8am and 8pm) in either Periods 1 or 2 are pooled in 1 group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 ng/kg over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. A final dose of PF-06282999 500 mg was administered on the evening of Day 3.

Units	Counts
Participants	OG0000 OG0010 OG0020

Primary

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

Due to early termination of the study, there was not enough participants to perform meaningful analysis on this endpoint. As such, no analysis was done.

Posted

Days 1, 3-5

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.

Primary

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

Due to early termination of the study, there was not enough participants to perform meaningful analysis on this endpoint. As such, no analysis was done.

Posted

Days 1, 3-5

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.

Primary

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

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.

All participants who received at least 1 dose of study medication (including LPS) were included in the safety analyses and listings.

Posted

Number

participants

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

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.

Primary

Number of Participants With Laboratory Test Abnormalities

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.

All participants who received at least 1 dose of study medication (including LPS) were included in the safety analyses and listings.

Posted

Number

participants

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

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.

Primary

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

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.

All participants who received at least 1 dose of study medication (including LPS) were included in the safety analyses and listings. n=number of participants evaluable for that parameter

Posted

Number

participants

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

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.

Primary

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

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.

All participants who received at least 1 dose of study medication (including LPS) were included in the safety analyses and listings.

Posted

Number

participants

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

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.

Primary

Number of Participants With Abnormal Urinary Biomarker Values

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

Analysis not done due to early termination of study.

Posted

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

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.
OG002	PF-06282999 500 mg BID

Secondary

Concentrations of TNF-alpha, IL-1 Beta, IL-6, IL-8, and hsCRP

The effect of multiple oral doses of PF-06282999 on inflammatory biomarkers was a secondary objective in this study. The biomarkers are tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and high-sensitivity C-reactive protein (hsCRP).

Due to early termination of the study, there was not enough participants to perform meaningful analysis on this endpoint. As such, no analysis was done.

Posted

Days 1, 3, and 4

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.

Secondary

Peak (AUC0.5-2hours and AUC0-2hours) of MPO Activity/MPO Mass

Due to early termination of the study, there was not enough participants to perform meaningful analysis on this endpoint. As such, no analysis was done.

Posted

Days 1, 3-5

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.

Secondary

Maximum Plasma Concentration (Cmax) of PF-06282999

Due to early termination of the study, there was not enough participants to perform meaningful analysis on this endpoint. As such, no analysis was done.

Posted

Day 3

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.
OG002	PF-06282999 500 mg BID	All participants who received PF-06282999 500 mg BID orally in tablet form from Days 1 to 3 (8am and 8pm) in either Periods 1 or 2 are pooled in 1 group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 ng/kg over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. A final dose of PF-06282999 500 mg was administered on the evening of Day 3.

Secondary

Area Under the Concentration-time Profile From Time 0 to End of Dosing Interval, Tau (AUCtau) of PF-06282999

Due to early termination of the study, no data was collected for this endpoint.

Posted

Day 3

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.
OG002	PF-06282999 500 mg BID	All participants who received PF-06282999 500 mg BID orally in tablet form from Days 1 to 3 (8am and 8pm) in either Periods 1 or 2 are pooled in 1 group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 ng/kg over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. A final dose of PF-06282999 500 mg was administered on the evening of Day 3.

Secondary

Time to Cmax (Tmax) of PF-06282999

Due to early termination of the study, no data was collected for this endpoint.

Posted

Day 3

ID	Title	Description
OG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.
OG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.
OG002	PF-06282999 500 mg BID	All participants who received PF-06282999 500 mg BID orally in tablet form from Days 1 to 3 (8am and 8pm) in either Periods 1 or 2 are pooled in 1 group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 ng/kg over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. A final dose of PF-06282999 500 mg was administered on the evening of Day 3.

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PF-06282999 125 mg TID	All participants who received PF-06282999 125 mg TID orally in tablet form from Days 1 to 3 (approximately 8am, 2pm, 8pm) in either Periods 1 or 2 are pooled in one group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 nanogram (ng)/kilogram (kg) over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. The final dose of PF-06282999 125 mg was administered on the evening of Day 3.	10	10	10
EG001	Placebo	All participants who received placebo in either Periods 1 or 2 are pooled in 1 group. Placebo matching either PF-06282999 125 mg TID or 500 mg twice daily (BID) were administered on Days 1-3 of each period. 2 hours after the morning dose on Day 3, LPS as IV bolus at a dose of 4 ng/kg over 45-60 secs was administered. The final dose of placebo was administered on the evening of Day 3.	19	17	19
EG002	PF-06282999 500 mg BID	All participants who received PF-06282999 500 mg BID orally in tablet form from Days 1 to 3 (8am and 8pm) in either Periods 1 or 2 are pooled in 1 group. On Day 3, participants received a dose of lipopolysaccharide (LPS) as an intravenous (IV) bolus at a dose of 4 ng/kg over 45-60 seconds (secs) 2 hours after the morning dose of PF-06282999. A final dose of PF-06282999 500 mg was administered on the evening of Day 3.	7	5	7

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bradycardia	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected19 at risk EG0020 affected7 at risk
Sinus arrest	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected19 at risk EG0020 affected7 at risk
Tachycardia	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0007 affected10 at risk EG00113 affected19 at risk EG0024 affected7 at risk
Eye pain	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected10 at risk EG0010 affected19 at risk EG0020 affected7 at risk
Dry mouth	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected19 at risk EG0020 affected7 at risk
Nausea	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected10 at risk EG0015 affected19 at risk EG0023 affected7 at risk
Vomiting	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected10 at risk EG0011 affected19 at risk EG0022 affected7 at risk
Chills	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0008 affected10 at risk EG00111 affected19 at risk EG0023 affected7 at risk
Fatigue	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected19 at risk EG0020 affected7 at risk
Pyrexia	General disorders	MedDRA v18.1	Non-systematic Assessment	EG00010 affected10 at risk EG00113 affected19 at risk EG0023 affected7 at risk
Body temperature increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected19 at risk EG0021 affected7 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected19 at risk EG0020 affected7 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0006 affected10 at risk EG0019 affected19 at risk EG0023 affected7 at risk
Headache	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0008 affected10 at risk EG00113 affected19 at risk EG0024 affected7 at risk
Lethargy	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected19 at risk EG0020 affected7 at risk
Paraesthesia	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected19 at risk EG0021 affected7 at risk
Presyncope	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected19 at risk EG0020 affected7 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected10 at risk EG0013 affected19 at risk EG0020 affected7 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected10 at risk EG0012 affected19 at risk EG0020 affected7 at risk
Hypotension	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0013 affected19 at risk EG0021 affected7 at risk
Pallor	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected19 at risk EG0020 affected7 at risk

ID	Term
C000605149	2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide
D004731	Endotoxins

ID	Term
D001427	Bacterial Toxins
D014118	Toxins, Biological
D001685	Biological Factors