Efficacy, Safety And Tolerability Of PF-06743649 In Gout Subjects.

A Randomized, Double Blind, Third Party Open, Placebo Controlled Multi-center Study Of Efficacy, Safety And Tolerability Of Pf-06743649 In Gout Subjects

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02187029

Enrollment

Registered

2014-07-10

Start date

2014-07-31

Completion date

2014-12-31

Last updated

2016-11-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gout

Keywords

Hyperuricemia, gout, serum uric acid

Brief summary

The purpose of the study is to assess the effect of PF-06743649 in lowering serum uric acid in subjects suffering from gout following 14 days of dosing, as well as assessing safety and tolerability.

Interventions

DRUGPF-06743649

Daily dosing (dose level 1) tablet for 14 days

OTHERPlacebo

Daily dosing (tablet) for 14 days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Inclusion criteria

* Subject meets the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of acute Arthritis of Primary Gout. * Subjects taking urate lowering therapy at the time of screening must be willing to discontinue their prior urate lowering therapy from the time of Screening Visit 1 until completion of the study period Day 16. * Subjects taking urate lowering therapy at the time of screening must have a serum urate level of \>= 8.0 mg/dL at time of the second screening visit. * Subjects NOT taking urate lowering therapy at the time of screening must have a serum urate level of \>= 8.0 mg/dL at both screening visits 1 and 2.

Exclusion criteria

* Positive medical history or current evidence of medical or psychiatric condition/disease, or ECG or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study. * Chronic kidney disease classified as moderate or severe (Clinical Practice Guideline, National Kidney Foundation)12; with GFR \< 60 mL/min/1.73m2 calculated by the Cockcroft-Gault equation. * Subjects with current tophaceous gout. * Gout flare that has not resolved for at least 2 weeks prior to randomization.

Design outcomes

Primary

Measure	Time frame	Description
Baseline of Serum Uric Acid	Baseline (pre-dose Day 1)	An elevation in serum uric acid, hyperuricemia, is a prerequisite for the development of gout.
Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14	Day 14 Hour 24	—
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to 28 days after last study drug administration (Day 42)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state AEs included both serious and non-serious events.
Number of Participants With Laboratory Test Abnormalities	Baseline up to follow up visit (Day 25-29)	Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters include hematology (Hemoglobin, Hematocrit, red blood cell \[RBC\] count, Platelet count, mean corpuscular volume \[MCV\], mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration \[MCHC\], white blood cell \[WBC\] count, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes), hematocrit (blood urea nitrogen \[BUN\]/urea and Creatinine, Glucose , Calcium, Sodium, Potassium, Chloride, Total CO2 \[Bicarbonate\], aspartate transaminase \[AST\], alanine transaminase \[ALT\], Total Bilirubin, Alkaline phosphatase, Albumin, Total protein, Thyroid Stimulating Hormone \[TSH\], free T3 \[FT3\] and free T4 \[FT4\] ), urinalysis (pH, Glucose \[qual\], Protein, Blood, Ketones, Nitrites, Leukocyte esterase, Urobilinogen, Urine bilirubin, Microscopy \[including crystals\]) and other (follicle-stimulating hormone \[FSH\], Urine drug screen).
Number of Participants With Potentially Clinically Significant Vital Signs Findings	Baseline up to follow up visit (Day 25-29)	Criteria for potential clinically important change in vital signs included: Systolic blood pressure (BP) less than (\<) 90 millimeters of mercury (mmHg) or more than or equal to (\>=)30 mmHg change from baseline, diastolic BP of \<50 mmHg or \>=20 mmHg change from baseline, Supine pulse rate of \<40 or more than (\>)120 beats per minute (bpm).
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	Baseline up to Day 16	Criteria for potential clinically important changes in ECG (12-lead) were defined as: 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) or increase from baseline \>=25% when baseline \>200 msec or increase from baseline \>=50% when baseline less than or equal to (\<=) 200 msec; time from the beginning of the electrocardiogram Q wave to the end of the S wave corresponding to ventricular depolarization (QRS) interval \>=140 msec or \>=50% increase from baseline; the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval 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 from baseline.

Secondary

Measure	Time frame	Description
Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Day 3, Day 7, Day 11, Day 14 and follow-up visit (Day 25-29)	—
Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	24 hours post dose on Day 7 and Day 14	Number of participants reaching serum uric acid levels \<6, \<5 and \<4 mg/dL at 7 and 14 days after initiation.
Incidence and Severity of Gout Flare Attacks	Baseline up to Day 42	—
Duration of Gout Flare Attacks	Baseline up to Day 42	Duration of gout flare attacks with participants who developed gout flare attacks.
Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	0, 1, 2, 4, 8, 12 and 24 hours at Day 1, Day 7, and Day 14	Data has been calculated by setting concentration values below the lower limit of quantification to zero. The lower limit of quantification was 10.0 nanograms per milliliter (ng/mL).
Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Day 7, and Day 14	PF-06743648 is an active metabolite of PF-06743649. Data has been calculated by setting concentration values below the lower limit of quantification to zero. The lower limit of quantification was 2.00 nanograms per milliliter (ng/mL).
Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline, Day 1, Day 7, Day 14, and at follow-up visit (Day 25-29)	Change in plasma levels of xanthine from baseline at time points 0 (prior to dosing except on Day 1), 1, 2, 4, 8, 12 and 24 hours following dosing with PF-06743649 or placebo on days 1, 7 and 14 as well prior to dosing on days 3 and 11 and at follow-up of treatment with PF-06743649 or placebo.
Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Day 7, Day 14, and at follow-up visit (Day 25-29)	—
Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Baseline, Day 1, Day 7 and Day 14	Change from baseline in urinary uric acid cumulative amounts.
Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Baseline, Day 1, Day 7 and Day 14	Change from baseline in urinary xanthine cumulative amounts.
Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Baseline, Day 1, Day 7 and Day 14	Change from baseline in urinary hypoxanthine cumulative amounts at Day 1, Day 7 and Day 14

Countries

United States

Participant flow

Participants by arm

Arm	Count
Cohort 1: PF-06743649 2.5 mg to 10 mg Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.	7
Cohort 1: PF-06743649 40 mg Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	3
Cohort 2: PF-06743649 5 mg Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.	11
Cohort 1 and 2: Placebo Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.	9
Total	30

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	1	1	0
Overall Study	Study Terminated by Sponsor	0	0	10	3
Overall Study	Withdrawal by Subject	1	0	0	0

Baseline characteristics

Characteristic	Cohort 1: PF-06743649 2.5 mg to 10 mg	Cohort 1: PF-06743649 40 mg	Cohort 2: PF-06743649 5 mg	Cohort 1 and 2: Placebo	Total
Age, Continuous	47.1 years STANDARD_DEVIATION 8.1	50.7 years STANDARD_DEVIATION 9.7	43.4 years STANDARD_DEVIATION 9.8	46.8 years STANDARD_DEVIATION 9.3	46.0 years STANDARD_DEVIATION 9.1
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	7 Participants	3 Participants	11 Participants	9 Participants	30 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	2 / 7	3 / 3	2 / 11	4 / 9
serious Total, serious adverse events	0 / 7	0 / 3	1 / 11	0 / 9

Outcome results

Primary

Baseline of Serum Uric Acid

An elevation in serum uric acid, hyperuricemia, is a prerequisite for the development of gout.

Time frame: Baseline (pre-dose Day 1)

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Baseline of Serum Uric Acid	8.800 milligram per deciliter(mg/dL)	Standard Deviation 1.1402
Cohort 1: PF-06743649 40 mg	Baseline of Serum Uric Acid	9.100 milligram per deciliter(mg/dL)	Standard Deviation 0.8185
Cohort 2: PF-06743649 5 mg	Baseline of Serum Uric Acid	8.991 milligram per deciliter(mg/dL)	Standard Deviation 0.6549
Cohort 1 and 2: Placebo	Baseline of Serum Uric Acid	9.278 milligram per deciliter(mg/dL)	Standard Deviation 0.9536

Primary

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

Criteria for potential clinically important changes in ECG (12-lead) were defined as: 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) or increase from baseline \>=25% when baseline \>200 msec or increase from baseline \>=50% when baseline less than or equal to (\<=) 200 msec; time from the beginning of the electrocardiogram Q wave to the end of the S wave corresponding to ventricular depolarization (QRS) interval \>=140 msec or \>=50% increase from baseline; the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval 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 from baseline.

Time frame: Baseline up to Day 16

Population: The safety analysis population included all participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QRS complex increase from baseline >=50%	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	PR increase from baseline >=25/50%	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF increase from baseline >=60 msec	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) 480-<500	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) 450-<480	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QRS complex (msec) >=140	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF increase from baseline 30 to <60 msec	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) >=500	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	PR (msec) >=300	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) >=500	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QRS complex increase from baseline >=50%	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	PR increase from baseline >=25/50%	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QRS complex (msec) >=140	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	PR (msec) >=300	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) 450-<480	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF increase from baseline >=60 msec	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF increase from baseline 30 to <60 msec	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) 480-<500	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) >=500	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	PR (msec) >=300	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QRS complex (msec) >=140	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) 450-<480	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) 480-<500	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	PR increase from baseline >=25/50%	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QRS complex increase from baseline >=50%	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF increase from baseline 30 to <60 msec	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF increase from baseline >=60 msec	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QRS complex increase from baseline >=50%	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) 480-<500	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) 450-<480	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF increase from baseline >=60 msec	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF increase from baseline 30 to <60 msec	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QRS complex (msec) >=140	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	PR increase from baseline >=25/50%	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	QTCF (msec) >=500	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria	PR (msec) >=300	0 participants

Primary

Number of Participants With Laboratory Test Abnormalities

Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters include hematology (Hemoglobin, Hematocrit, red blood cell \[RBC\] count, Platelet count, mean corpuscular volume \[MCV\], mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration \[MCHC\], white blood cell \[WBC\] count, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes), hematocrit (blood urea nitrogen \[BUN\]/urea and Creatinine, Glucose , Calcium, Sodium, Potassium, Chloride, Total CO2 \[Bicarbonate\], aspartate transaminase \[AST\], alanine transaminase \[ALT\], Total Bilirubin, Alkaline phosphatase, Albumin, Total protein, Thyroid Stimulating Hormone \[TSH\], free T3 \[FT3\] and free T4 \[FT4\] ), urinalysis (pH, Glucose \[qual\], Protein, Blood, Ketones, Nitrites, Leukocyte esterase, Urobilinogen, Urine bilirubin, Microscopy \[including crystals\]) and other (follicle-stimulating hormone \[FSH\], Urine drug screen).

Time frame: Baseline up to follow up visit (Day 25-29)

Population: The safety analysis population included all participants who received at least 1 dose of study medication.

Arm	Measure	Value (NUMBER)
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Laboratory Test Abnormalities	1 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Laboratory Test Abnormalities	1 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Laboratory Test Abnormalities	3 participants
Cohort 1 and 2: Placebo	Number of Participants With Laboratory Test Abnormalities	2 participants

Primary

Number of Participants With Potentially Clinically Significant Vital Signs Findings

Criteria for potential clinically important change in vital signs included: Systolic blood pressure (BP) less than (\<) 90 millimeters of mercury (mmHg) or more than or equal to (\>=)30 mmHg change from baseline, diastolic BP of \<50 mmHg or \>=20 mmHg change from baseline, Supine pulse rate of \<40 or more than (\>)120 beats per minute (bpm).

Time frame: Baseline up to follow up visit (Day 25-29)

Population: The safety analysis population included all participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Systolic BP (mmHg) <90	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Diastolic BP (mmHg) <50	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Pulse Rate (bpm) <40	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Pulse Rate (bpm) >120	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Increase Supine Systolic BP (mmHg) >=30	1 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Increase Supine Diastolic BP (mmHg) >=20	1 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Decrease Supine Systolic BP (mmHg) >=30	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Decrease Supine Diastolic BP (mmHg) >=20	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Pulse Rate (bpm) >120	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Systolic BP (mmHg) <90	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Diastolic BP (mmHg) <50	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Pulse Rate (bpm) <40	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Decrease Supine Diastolic BP (mmHg) >=20	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Increase Supine Systolic BP (mmHg) >=30	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Increase Supine Diastolic BP (mmHg) >=20	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Decrease Supine Systolic BP (mmHg) >=30	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Pulse Rate (bpm) <40	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Increase Supine Diastolic BP (mmHg) >=20	1 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Systolic BP (mmHg) <90	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Pulse Rate (bpm) >120	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Decrease Supine Systolic BP (mmHg) >=30	1 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Increase Supine Systolic BP (mmHg) >=30	1 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Diastolic BP (mmHg) <50	0 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Decrease Supine Diastolic BP (mmHg) >=20	1 participants
Cohort 1 and 2: Placebo	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Diastolic BP (mmHg) <50	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Pulse Rate (bpm) <40	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Increase Supine Systolic BP (mmHg) >=30	1 participants
Cohort 1 and 2: Placebo	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Pulse Rate (bpm) >120	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Increase Supine Diastolic BP (mmHg) >=20	1 participants
Cohort 1 and 2: Placebo	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Decrease Supine Diastolic BP (mmHg) >=20	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Supine Systolic BP (mmHg) <90	0 participants
Cohort 1 and 2: Placebo	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Decrease Supine Systolic BP (mmHg) >=30	0 participants

Primary

Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state AEs included both serious and non-serious events.

Time frame: Baseline up to 28 days after last study drug administration (Day 42)

Population: The safety analysis population included all participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Participants with AEs	2 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Participants with SAEs	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Participants with SAEs	0 participants
Cohort 1: PF-06743649 40 mg	Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Participants with AEs	3 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Participants with AEs	3 participants
Cohort 2: PF-06743649 5 mg	Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Participants with SAEs	1 participants
Cohort 1 and 2: Placebo	Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Participants with AEs	4 participants
Cohort 1 and 2: Placebo	Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Participants with SAEs	0 participants

Primary

Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14

Time frame: Day 14 Hour 24

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment. Number of participants analyzed is number of evaluable participants for this outcome measure. No data due to Cohort 2: PF-06743649 5 mg termination after 2 days of dosing.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14	-52.891 percent (%)	Standard Deviation 6.1661
Cohort 1: PF-06743649 40 mg	Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14	-67.480 percent (%)	Standard Deviation 1.1498
Cohort 1 and 2: Placebo	Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14	-1.381 percent (%)	Standard Deviation 9.143

90% CI: [-56.32, -48.78]Bayesian ANCOVA

90% CI: [-71.31, -61.54]Bayesian ANCOVA

Secondary

Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up

Time frame: Day 1, Day 7, Day 14, and at follow-up visit (Day 25-29)

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-0.2860 mcg/mL	Standard Deviation 0.21522
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 8 (n=7,2,0,6)	-0.2610 mcg/mL	Standard Deviation 0.30443
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 24 (n=7,3,11,9)	-0.0937 mcg/mL	Standard Deviation 0.30529
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 8 (n=6,2,0,6)	-0.2898 mcg/mL	Standard Deviation 0.3212
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 4 (n=7,2,0,6)	-0.0067 mcg/mL	Standard Deviation 0.28262
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 2 (n=7,2,0,6)	-0.0923 mcg/mL	Standard Deviation 0.11659
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, pre-dose (n=7,2,0,6)	-0.1309 mcg/mL	Standard Deviation 0.31653
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-0.2229 mcg/mL	Standard Deviation 0.08132
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 1 (n=7,2,0,6)	-0.1089 mcg/mL	Standard Deviation 0.40558
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 24 (n=6,2,0,6)	-0.2030 mcg/mL	Standard Deviation 0.23638
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 4 (n=6,2,0,6)	-0.3627 mcg/mL	Standard Deviation 0.22065
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline (n=7,3,11,9)	0.9604 mcg/mL	Standard Deviation 0.1538
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-0.2774 mcg/mL	Standard Deviation 0.19696
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 1 (n=7,3,11,9)	-0.2539 mcg/mL	Standard Deviation 0.24173
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 2 (n=6,2,0,6)	-0.1970 mcg/mL	Standard Deviation 0.2011
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 1 (n=6,2,0,6)	-0.2292 mcg/mL	Standard Deviation 0.13816
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-0.2000 mcg/mL	Standard Deviation 0.27433
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Follow-up Day 25-29 (n=6,3,10,9)	-0.0965 mcg/mL	Standard Deviation 0.43007
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, pre-dose (n=6,2,0,6)	-0.2573 mcg/mL	Standard Deviation 0.23823
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 24 (n=7,2,0,6)	-0.1926 mcg/mL	Standard Deviation 0.18082
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-0.2973 mcg/mL	Standard Deviation 0.13666
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 12 (n=6,2,0,6)	-0.2415 mcg/mL	Standard Deviation 0.19015
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 2 (n=6,2,0,6)	0.2860 mcg/mL	Standard Deviation 0.29133
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline (n=7,3,11,9)	1.0060 mcg/mL	Standard Deviation 0.41079
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 1 (n=7,3,11,9)	0.1440 mcg/mL	Standard Deviation 0.56564
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 2 (n=7,3,11,9)	0.2130 mcg/mL	Standard Deviation 0.40812
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 4 (n=7,3,11,9)	0.0717 mcg/mL	Standard Deviation 0.62608
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 8 (n=7,3,11,9)	0.1760 mcg/mL	Standard Deviation 0.78402
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 12 (n=7,3,11,9)	0.2703 mcg/mL	Standard Deviation 0.62935
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 24 (n=7,3,11,9)	0.5607 mcg/mL	Standard Deviation 0.66507
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, pre-dose (n=7,2,0,6)	0.0810 mcg/mL	Standard Deviation 0.21355
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 1 (n=7,2,0,6)	-0.1575 mcg/mL	Standard Deviation 0.46598
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 2 (n=7,2,0,6)	0.1360 mcg/mL	Standard Deviation 0.67317
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 4 (n=7,2,0,6)	-0.2505 mcg/mL	Standard Deviation 0.37406
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 8 (n=7,2,0,6)	-0.0495 mcg/mL	Standard Deviation 0.61023
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-0.5290 mcg/mL	Standard Deviation 0.32951
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 24 (n=7,2,0,6)	0.1410 mcg/mL	Standard Deviation 0.68024
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, pre-dose (n=6,2,0,6)	0.0710 mcg/mL	Standard Deviation 0.24183
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 1 (n=6,2,0,6)	0.1660 mcg/mL	Standard Deviation 0.30547
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 4 (n=6,2,0,6)	0.1210 mcg/mL	Standard Deviation 0.42568
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 8 (n=6,2,0,6)	-0.2310 mcg/mL	Standard Deviation 0.16829
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 12 (n=6,2,0,6)	0.0510 mcg/mL	Standard Deviation 0.11455
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 24 (n=6,2,0,6)	0.2260 mcg/mL	Standard Deviation 0.36204
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Follow-up Day 25-29 (n=6,3,10,9)	-0.2550 mcg/mL	Standard Deviation 0.91149
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 2 (n=6,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 12 (n=7,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-0.0145 mcg/mL	Standard Deviation 0.13714
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-0.1895 mcg/mL	Standard Deviation 0.18641
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 4 (n=6,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Follow-up Day 25-29 (n=6,3,10,9)	0.3204 mcg/mL	Standard Deviation 0.30373
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, pre-dose (n=6,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline (n=7,3,11,9)	0.8677 mcg/mL	Standard Deviation 0.18896
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 8 (n=6,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 12 (n=6,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, pre-dose (n=7,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-0.0979 mcg/mL	Standard Deviation 0.15883
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 1 (n=7,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 24 (n=6,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 1 (n=6,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 1 (n=7,3,11,9)	-0.1205 mcg/mL	Standard Deviation 0.16427
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 2 (n=7,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 8 (n=7,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 24 (n=7,3,11,9)	-0.0039 mcg/mL	Standard Deviation 0.10751
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-0.1426 mcg/mL	Standard Deviation 0.14932
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 4 (n=7,2,0,6)	NA mcg/mL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 24 (n=7,2,0,6)	NA mcg/mL	—
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 4 (n=7,2,0,6)	0.0762 mcg/mL	Standard Deviation 0.37371
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 8 (n=7,2,0,6)	-0.0543 mcg/mL	Standard Deviation 0.35172
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 12 (n=6,2,0,6)	-0.1075 mcg/mL	Standard Deviation 0.20019
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-0.1557 mcg/mL	Standard Deviation 0.15279
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-0.1870 mcg/mL	Standard Deviation 0.26137
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline (n=7,3,11,9)	0.8922 mcg/mL	Standard Deviation 0.13486
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 24 (n=7,2,0,6)	-0.0680 mcg/mL	Standard Deviation 0.35421
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, pre-dose (n=6,2,0,6)	-0.0978 mcg/mL	Standard Deviation 0.10319
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-0.0369 mcg/mL	Standard Deviation 0.32185
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 1 (n=6,2,0,6)	-0.1065 mcg/mL	Standard Deviation 0.19276
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-0.0421 mcg/mL	Standard Deviation 0.21113
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 2 (n=6,2,0,6)	0.0047 mcg/mL	Standard Deviation 0.25228
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 24 (n=6,2,0,6)	0.0855 mcg/mL	Standard Deviation 0.3631
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 4 (n=6,2,0,6)	0.0133 mcg/mL	Standard Deviation 0.30407
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 1 (n=7,3,11,9)	0.0847 mcg/mL	Standard Deviation 0.41097
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, pre-dose (n=7,2,0,6)	0.1317 mcg/mL	Standard Deviation 0.57974
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 8 (n=6,2,0,6)	-0.0698 mcg/mL	Standard Deviation 0.34513
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 1 (n=7,2,0,6)	-0.0285 mcg/mL	Standard Deviation 0.43096
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 24 (n=7,3,11,9)	0.1200 mcg/mL	Standard Deviation 0.489
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 2 (n=7,2,0,6)	-0.0103 mcg/mL	Standard Deviation 0.35162
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Follow-up Day 25-29 (n=6,3,10,9)	0.3778 mcg/mL	Standard Deviation 0.73741
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-0.0967 mcg/mL	Standard Deviation 0.22579

Comparison: Day 1, Hour 190% CI: [-0.707, 0.01]Mixed Models Analysis

Comparison: Day 1, Hour 290% CI: [-0.533, 0.175]Mixed Models Analysis

Comparison: Day 1, Hour 490% CI: [-0.568, 0.052]Mixed Models Analysis

Comparison: Day 1, Hour 890% CI: [-0.39, 0.298]Mixed Models Analysis

Comparison: Day 1, Hour 1290% CI: [-0.575, 0.006]Mixed Models Analysis

Comparison: Day 1, Hour 2490% CI: [-0.569, 0.237]Mixed Models Analysis

Comparison: Day 7, pre-dose90% CI: [-0.657, 0.132]Mixed Models Analysis

Comparison: Day 7, Hour 190% CI: [-0.46, 0.299]Mixed Models Analysis

Comparison: Day 7, Hour 290% CI: [-0.392, 0.228]Mixed Models Analysis

Comparison: Day 7, Hour 490% CI: [-0.408, 0.242]Mixed Models Analysis

Comparison: Day 7, Hour 890% CI: [-0.508, 0.095]Mixed Models Analysis

Comparison: Day 7, Hour 1290% CI: [-0.451, 0.191]Mixed Models Analysis

Comparison: Day 7, Hour 2490% CI: [-0.445, 0.196]Mixed Models Analysis

Comparison: Day 14, pre-dose90% CI: [-0.472, 0.097]Mixed Models Analysis

Comparison: Day 14, Hour 190% CI: [-0.434, 0.13]Mixed Models Analysis

Comparison: Day 14, Hour 290% CI: [-0.504, 0.043]Mixed Models Analysis

Comparison: Day 14, Hour 490% CI: [-0.722, -0.088]Mixed Models Analysis

Comparison: Day 14, Hour 890% CI: [-0.56, 0.062]Mixed Models Analysis

Comparison: Day 14, Hour 1290% CI: [-0.467, 0.141]Mixed Models Analysis

Comparison: Day 14, Hour 2490% CI: [-0.633, -0.002]Mixed Models Analysis

Comparison: Follow-up, Day 25-2990% CI: [-0.683, 0.496]Mixed Models Analysis

Comparison: Day 1, Hour 190% CI: [-0.406, 0.505]Mixed Models Analysis

Comparison: Day 1, Hour 290% CI: [-0.193, 0.707]Mixed Models Analysis

Comparison: Day 1, Hour 490% CI: [-0.302, 0.485]Mixed Models Analysis

Comparison: Day 1, Hour 890% CI: [-0.107, 0.768]Mixed Models Analysis

Comparison: Day 1, Hour 1290% CI: [-0.087, 0.653]Mixed Models Analysis

Comparison: Day 1, Hour 2490% CI: [-0.024, 1]Mixed Models Analysis

Comparison: Day 7, pre-dose90% CI: [-0.356, 0.768]Mixed Models Analysis

Comparison: Day 7, Hour 190% CI: [-0.41, 0.656]Mixed Models Analysis

Comparison: Day 7, Hour 290% CI: [-0.025, 0.818]Mixed Models Analysis

Comparison: Day 7, Hour 490% CI: [-0.523, 0.368]Mixed Models Analysis

Comparison: Day 7, Hour 890% CI: [-0.154, 0.661]Mixed Models Analysis

Comparison: Day 7, Hour 1290% CI: [-0.564, 0.315]Mixed Models Analysis

Comparison: Day 7, Hour 2490% CI: [0.019, 0.897]Mixed Models Analysis

Comparison: Day 14, pre-dose90% CI: [0.043, 0.792]Mixed Models Analysis

Comparison: Day 14, Hour 190% CI: [0.15, 0.893]Mixed Models Analysis

Comparison: Day 14, Hour 290% CI: [0.172, 0.888]Mixed Models Analysis

Comparison: Day 14, Hour 490% CI: [-0.069, 0.782]Mixed Models Analysis

Comparison: Day 14, Hour 890% CI: [-0.328, 0.503]Mixed Models Analysis

Comparison: Day 14, Hour 1290% CI: [0, 0.812]Mixed Models Analysis

Comparison: Day 14, Hour 2490% CI: [-0.047, 0.802]Mixed Models Analysis

Comparison: Follow-up, Day 25-2990% CI: [-0.949, 0.502]Mixed Models Analysis

Secondary

Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up

Change in plasma levels of xanthine from baseline at time points 0 (prior to dosing except on Day 1), 1, 2, 4, 8, 12 and 24 hours following dosing with PF-06743649 or placebo on days 1, 7 and 14 as well prior to dosing on days 3 and 11 and at follow-up of treatment with PF-06743649 or placebo.

Time frame: Baseline, Day 1, Day 7, Day 14, and at follow-up visit (Day 25-29)

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-0.1276 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04658
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 8 (n=7,2,0,6)	-0.1086 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04749
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 24 (n=7,3,11,9)	0.0167 micrograms per milliliter (mcg/mL)	Standard Deviation 0.08149
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 8 (n=6,2,0,6)	-0.0655 micrograms per milliliter (mcg/mL)	Standard Deviation 0.08041
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 4 (n=7,2,0,6)	-0.0147 micrograms per milliliter (mcg/mL)	Standard Deviation 0.06839
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 2 (n=7,2,0,6)	0.0231 micrograms per milliliter (mcg/mL)	Standard Deviation 0.0507
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, pre-dose (n=7,2,0,6)	-0.0362 micrograms per milliliter (mcg/mL)	Standard Deviation 0.07118
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-0.0330 micrograms per milliliter (mcg/mL)	Standard Deviation 0.03844
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 1 (n=7,2,0,6)	-0.0061 micrograms per milliliter (mcg/mL)	Standard Deviation 0.10488
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 24 (n=6,2,0,6)	-0.0172 micrograms per milliliter (mcg/mL)	Standard Deviation 0.08536
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 4 (n=6,2,0,6)	-0.0148 micrograms per milliliter (mcg/mL)	Standard Deviation 0.09997
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline (n=7,3,11,9)	0.2519 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04316
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-0.0826 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04922
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 1 (n=7,3,11,9)	-0.0473 micrograms per milliliter (mcg/mL)	Standard Deviation 0.05949
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 2 (n=6,2,0,6)	0.1353 micrograms per milliliter (mcg/mL)	Standard Deviation 0.0901
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 1 (n=6,2,0,6)	0.0607 micrograms per milliliter (mcg/mL)	Standard Deviation 0.06662
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-0.0859 micrograms per milliliter (mcg/mL)	Standard Deviation 0.07603
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Follow-up (Day 25-29) (n=6,3,10,9)	0.3710 micrograms per milliliter (mcg/mL)	Standard Deviation 0.92324
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, pre-dose (n=6,2,0,6)	-0.0290 micrograms per milliliter (mcg/mL)	Standard Deviation 0.05418
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 24 (n=7,2,0,6)	-0.0540 micrograms per milliliter (mcg/mL)	Standard Deviation 0.05434
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-0.1117 micrograms per milliliter (mcg/mL)	Standard Deviation 0.0427
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 12 (n=6,2,0,6)	-0.0986 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04973
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 2 (n=6,2,0,6)	0.5960 micrograms per milliliter (mcg/mL)	Standard Deviation 0.01131
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline (n=7,3,11,9)	0.2680 micrograms per milliliter (mcg/mL)	Standard Deviation 0.10095
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 1 (n=7,3,11,9)	0.1057 micrograms per milliliter (mcg/mL)	Standard Deviation 0.02155
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 2 (n=7,3,11,9)	0.3667 micrograms per milliliter (mcg/mL)	Standard Deviation 0.27216
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 4 (n=7,3,11,9)	0.3317 micrograms per milliliter (mcg/mL)	Standard Deviation 0.11558
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 8 (n=7,3,11,9)	0.1947 micrograms per milliliter (mcg/mL)	Standard Deviation 0.14431
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 12 (n=7,3,11,9)	0.0847 micrograms per milliliter (mcg/mL)	Standard Deviation 0.11634
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 24 (n=7,3,11,9)	0.1927 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04879
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, pre-dose (n=7,2,0,6)	0.1450 micrograms per milliliter (mcg/mL)	Standard Deviation 0.00283
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 1 (n=7,2,0,6)	0.1765 micrograms per milliliter (mcg/mL)	Standard Deviation 0.07566
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 2 (n=7,2,0,6)	0.5300 micrograms per milliliter (mcg/mL)	Standard Deviation 0.21779
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 4 (n=7,2,0,6)	0.4995 micrograms per milliliter (mcg/mL)	Standard Deviation 0.1492
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 8 (n=7,2,0,6)	0.3010 micrograms per milliliter (mcg/mL)	Standard Deviation 0.14425
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-0.0535 micrograms per milliliter (mcg/mL)	Standard Deviation 0.01909
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 24 (n=7,2,0,6)	0.1465 micrograms per milliliter (mcg/mL)	Standard Deviation 0.0799
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, pre-dose (n=6,2,0,6)	0.1540 micrograms per milliliter (mcg/mL)	Standard Deviation 0.07778
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 1 (n=6,2,0,6)	0.3515 micrograms per milliliter (mcg/mL)	Standard Deviation 0.10819
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 4 (n=6,2,0,6)	0.5595 micrograms per milliliter (mcg/mL)	Standard Deviation 0.00212
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 8 (n=6,2,0,6)	0.2030 micrograms per milliliter (mcg/mL)	Standard Deviation 0.11738
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 12 (n=6,2,0,6)	0.1175 micrograms per milliliter (mcg/mL)	Standard Deviation 0.18031
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 24 (n=6,2,0,6)	0.1695 micrograms per milliliter (mcg/mL)	Standard Deviation 0.08132
Cohort 1: PF-06743649 40 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Follow-up (Day 25-29) (n=6,3,10,9)	0.8263 micrograms per milliliter (mcg/mL)	Standard Deviation 0.77448
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 2 (n=6,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 12 (n=7,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 2 (n=7,3,11,9)	0.0346 micrograms per milliliter (mcg/mL)	Standard Deviation 0.0509
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-0.0918 micrograms per milliliter (mcg/mL)	Standard Deviation 0.02295
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 4 (n=6,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Follow-up (Day 25-29) (n=6,3,10,9)	0.1161 micrograms per milliliter (mcg/mL)	Standard Deviation 0.18229
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, pre-dose (n=6,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline (n=7,3,11,9)	0.2102 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04037
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 8 (n=6,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 12 (n=6,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, pre-dose (n=7,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-0.0921 micrograms per milliliter (mcg/mL)	Standard Deviation 0.03801
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 1 (n=7,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 24 (n=6,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 1 (n=6,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 1 (n=7,3,11,9)	-0.0192 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04214
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 2 (n=7,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 8 (n=7,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 24 (n=7,3,11,9)	0.0140 micrograms per milliliter (mcg/mL)	Standard Deviation 0.03411
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-0.0306 micrograms per milliliter (mcg/mL)	Standard Deviation 0.05783
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 4 (n=7,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 24 (n=7,2,0,6)	NA micrograms per milliliter (mcg/mL)	—
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 4 (n=7,2,0,6)	-0.0233 micrograms per milliliter (mcg/mL)	Standard Deviation 0.07942
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 8 (n=7,2,0,6)	-0.0843 micrograms per milliliter (mcg/mL)	Standard Deviation 0.05064
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 12 (n=6,2,0,6)	-0.0801 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04477
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-0.0750 micrograms per milliliter (mcg/mL)	Standard Deviation 0.04685
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-0.0982 micrograms per milliliter (mcg/mL)	Standard Deviation 0.3674
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Baseline (n=7,3,11,9)	0.2257 micrograms per milliliter (mcg/mL)	Standard Deviation 0.05304
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 24 (n=7,2,0,6)	-0.0242 micrograms per milliliter (mcg/mL)	Standard Deviation 0.06072
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, pre-dose (n=6,2,0,6)	-0.0120 micrograms per milliliter (mcg/mL)	Standard Deviation 0.02367
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-0.0511 micrograms per milliliter (mcg/mL)	Standard Deviation 0.0651
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 1 (n=6,2,0,6)	-0.0008 micrograms per milliliter (mcg/mL)	Standard Deviation 0.02699
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-0.0220 micrograms per milliliter (mcg/mL)	Standard Deviation 0.03653
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 2 (n=6,2,0,6)	0.0330 micrograms per milliliter (mcg/mL)	Standard Deviation 0.09579
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 24 (n=6,2,0,6)	0.0242 micrograms per milliliter (mcg/mL)	Standard Deviation 0.06158
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 4 (n=6,2,0,6)	-0.0210 micrograms per milliliter (mcg/mL)	Standard Deviation 0.07869
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 1 (n=7,3,11,9)	-0.0112 micrograms per milliliter (mcg/mL)	Standard Deviation 0.0823
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, pre-dose (n=7,2,0,6)	0.0177 micrograms per milliliter (mcg/mL)	Standard Deviation 0.13598
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 14, Hour 8 (n=6,2,0,6)	-0.0778 micrograms per milliliter (mcg/mL)	Standard Deviation 0.06107
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 1 (n=7,2,0,6)	-0.0170 micrograms per milliliter (mcg/mL)	Standard Deviation 0.07475
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 24 (n=7,3,11,9)	0.0233 micrograms per milliliter (mcg/mL)	Standard Deviation 0.10687
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 7, Hour 2 (n=7,2,0,6)	-0.0098 micrograms per milliliter (mcg/mL)	Standard Deviation 0.08066
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Follow-up (Day 25-29) (n=6,3,10,9)	0.2299 micrograms per milliliter (mcg/mL)	Standard Deviation 0.44888
Cohort 1 and 2: Placebo	Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-0.0786 micrograms per milliliter (mcg/mL)	Standard Deviation 0.05731

Comparison: Day 1, Hour 190% CI: [-0.1103, 0.0394]Mixed Models Analysis

Comparison: Day 1, Hour 290% CI: [-0.1269, 0.0966]Mixed Models Analysis

Comparison: Day 1, Hour 490% CI: [-0.1078, 0.0417]Mixed Models Analysis

Comparison: Day 1, Hour 890% CI: [-0.075, 0.082]Mixed Models Analysis

Comparison: Day 1, Hour 1290% CI: [-0.1153, 0.0149]Mixed Models Analysis

Comparison: Day 1, Hour 2490% CI: [-0.1058, 0.0899]Mixed Models Analysis

Comparison: Day 7, pre-dose90% CI: [-0.1538, 0.046]Mixed Models Analysis

Comparison: Day 7, Hour 190% CI: [-0.0793, 0.101]Mixed Models Analysis

Comparison: Day 7, Hour 290% CI: [-0.0554, 0.1213]Mixed Models Analysis

Comparison: Day 7, Hour 490% CI: [-0.0733, 0.0905]Mixed Models Analysis

Comparison: Day 7, Hour 890% CI: [-0.0865, 0.0378]Mixed Models Analysis

Comparison: Day 7, Hour 1290% CI: [-0.0973, -0.0079]Mixed Models Analysis

Comparison: Day 7, Hour 2490% CI: [-0.0889, 0.0292]Mixed Models Analysis

Comparison: Day 14, pre-dose90% CI: [-0.0649, 0.0315]Mixed Models Analysis

Comparison: Day 14, Hour 190% CI: [0.001, 0.1222]Mixed Models Analysis

Comparison: Day 14, Hour 290% CI: [0.0104, 0.1945]Mixed Models Analysis

Comparison: Day 14, Hour 490% CI: [-0.0827, 0.0952]Mixed Models Analysis

Comparison: Day 14, Hour 890% CI: [-0.0672, 0.0919]Mixed Models Analysis

Comparison: Day 14, Hour 1290% CI: [-0.0918, 0.0547]Mixed Models Analysis

Comparison: Day 14, Hour 2490% CI: [-0.1192, 0.0365]Mixed Models Analysis

Comparison: Follow-up, Day 25-2990% CI: [-0.2968, 1.099]Mixed Models Analysis

Comparison: Day 1, Hour 190% CI: [0.0223, 0.2127]Mixed Models Analysis

Comparison: Day 1, Hour 290% CI: [0.2424, 0.5266]Mixed Models Analysis

Comparison: Day 1, Hour 490% CI: [0.2862, 0.4762]Mixed Models Analysis

Comparison: Day 1, Hour 890% CI: [0.1843, 0.3838]Mixed Models Analysis

Comparison: Day 1, Hour 1290% CI: [0.0635, 0.2289]Mixed Models Analysis

Comparison: Day 1, Hour 2490% CI: [0.0436, 0.2924]Mixed Models Analysis

Comparison: Day 7, pre-dose90% CI: [-0.0172, 0.2778]Mixed Models Analysis

Comparison: Day 7, Hour 190% CI: [0.0625, 0.3281]Mixed Models Analysis

Comparison: Day 7, Hour 290% CI: [0.411, 0.6707]Mixed Models Analysis

Comparison: Day 7, Hour 490% CI: [0.4032, 0.6438]Mixed Models Analysis

Comparison: Day 7, Hour 890% CI: [0.2944, 0.4769]Mixed Models Analysis

Comparison: Day 7, Hour 1290% CI: [-0.0439, 0.0872]Mixed Models Analysis

Comparison: Day 7, Hour 2490% CI: [0.0841, 0.2574]Mixed Models Analysis

Comparison: Day 14, pre-dose90% CI: [0.0982, 0.2338]Mixed Models Analysis

Comparison: Day 14, Hour 190% CI: [0.2667, 0.438]Mixed Models Analysis

Comparison: Day 14, Hour 290% CI: [0.433, 0.6932]Mixed Models Analysis

Comparison: Day 14, Hour 490% CI: [0.4549, 0.7065]Mixed Models Analysis

Comparison: Day 14, Hour 890% CI: [0.1688, 0.394]Mixed Models Analysis

Comparison: Day 14, Hour 1290% CI: [0.0945, 0.3019]Mixed Models Analysis

Comparison: Day 14, Hour 2490% CI: [0.0361, 0.2569]Mixed Models Analysis

Comparison: Follow-up, Day 25-2990% CI: [0.0017, 1.7112]Mixed Models Analysis

Secondary

Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up

Time frame: Day 1, Day 3, Day 7, Day 11, Day 14 and follow-up visit (Day 25-29)

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 24 (n=7,3,11,9)	-1.69 mg/dL	Standard Deviation 0.664
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 1 (n=6,3,11, 9)	-0.18 mg/dL	Standard Deviation 0.194
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-0.69 mg/dL	Standard Deviation 0.261
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-1.47 mg/dL	Standard Deviation 0.293
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-2.00 mg/dL	Standard Deviation 0.716
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-1.77 mg/dL	Standard Deviation 0.704
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Baseline (n=7,3,11,9)	8.80 mg/dL	Standard Deviation 1.14
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 3 (n=7,3,10,9)	-2.13 mg/dL	Standard Deviation 0.921
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, pre-dose (n=7,2,0,6)	-2.60 mg/dL	Standard Deviation 0.945
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 1 (n=7,2,0,6)	-2.64 mg/dL	Standard Deviation 0.846
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 2 (n=7,2,0,6)	-2.94 mg/dL	Standard Deviation 0.838
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 4 (n=7,2,0,6)	-3.44 mg/dL	Standard Deviation 0.873
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 8 (n=7,2,0,6)	-3.49 mg/dL	Standard Deviation 0.996
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-3.24 mg/dL	Standard Deviation 1.037
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 24 (n=7,2,0,6)	-2.73 mg/dL	Standard Deviation 0.955
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 11 (n=6,2,0,6)	-4.80 mg/dL	Standard Deviation 0.961
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, pre-dose (n=6,2,0,6)	-4.57 mg/dL	Standard Deviation 0.9
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 1 (n=6,2,0,6)	-4.83 mg/dL	Standard Deviation 0.799
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 2 (n=6,2,0,6)	-5.35 mg/dL	Standard Deviation 0.846
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 4 (n=6,2,0,6)	-6.02 mg/dL	Standard Deviation 0.906
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 8 (n=6,2,0,6)	-5.93 mg/dL	Standard Deviation 1.001
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 12 (n=6,2,0,6)	-5.67 mg/dL	Standard Deviation 1.124
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 24 (n=6,2,0,6)	-4.85 mg/dL	Standard Deviation 0.94
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Follow-up (Day 25-29) (n=6,3,10,9)	-0.93 mg/dL	Standard Deviation 1.422
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Follow-up (Day 25-29) (n=6,3,10,9)	-2.27 mg/dL	Standard Deviation 2.593
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 8 (n=7,2,0,6)	-6.60 mg/dL	Standard Deviation 0.141
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, pre-dose (n=7,2,0,6)	-5.75 mg/dL	Standard Deviation 0.212
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 1 (n=6,2,0,6)	-6.05 mg/dL	Standard Deviation 0.495
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 12 (n=6,2,0,6)	-6.60 mg/dL	Standard Deviation 0.566
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-6.45 mg/dL	Standard Deviation 0.071
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-3.83 mg/dL	Standard Deviation 0.577
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, pre-dose (n=6,2,0,6)	-5.75 mg/dL	Standard Deviation 0.636
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-3.07 mg/dL	Standard Deviation 0.115
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 24 (n=7,2,0,6)	-5.90 mg/dL	Standard Deviation 0.141
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 8 (n=6,2,0,6)	-6.85 mg/dL	Standard Deviation 0.636
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 24 (n=6,2,0,6)	-5.90 mg/dL	Standard Deviation 0.424
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 11 (n=6,2,0,6)	-5.75 mg/dL	Standard Deviation 0.071
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 1 (n=7,2,0,6)	-5.75 mg/dL	Standard Deviation 0.212
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 4 (n=6,2,0,6)	-6.80 mg/dL	Standard Deviation 0.566
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-1.17 mg/dL	Standard Deviation 0.839
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 3 (n=7,3,10,9)	-4.50 mg/dL	Standard Deviation 0.529
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 2 (n=7,2,0,6)	-6.10 mg/dL	Standard Deviation 0.283
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 24 (n=7,3,11,9)	-3.43 mg/dL	Standard Deviation 0.757
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 1 (n=6,3,11, 9)	-0.50 mg/dL	Standard Deviation 0.436
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 2 (n=6,2,0,6)	-6.35 mg/dL	Standard Deviation 0.495
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 4 (n=7,2,0,6)	-6.60 mg/dL	Standard Deviation 0.283
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-3.87 mg/dL	Standard Deviation 0.473
Cohort 1: PF-06743649 40 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Baseline (n=7,3,11,9)	9.10 mg/dL	Standard Deviation 0.819
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 2 (n=7,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 24 (n=7,3,11,9)	-2.04 mg/dL	Standard Deviation 0.77
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 3 (n=7,3,10,9)	-3.02 mg/dL	Standard Deviation 0.925
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, pre-dose (n=7,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 1 (n=7,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 8 (n=6,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 4 (n=6,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 4 (n=7,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Follow-up (Day 25-29) (n=6,3,10,9)	0.45 mg/dL	Standard Deviation 0.938
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 8 (n=7,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 12 (n=7,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 12 (n=6,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 24 (n=7,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 11 (n=6,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, pre-dose (n=6,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 24 (n=6,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 1 (n=6,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Baseline (n=7,3,11,9)	8.99 mg/dL	Standard Deviation 0.655
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 1 (n=6,3,11, 9)	-0.51 mg/dL	Standard Deviation 0.353
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 2 (n=6,2,0,6)	NA mg/dL	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-1.27 mg/dL	Standard Deviation 0.403
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-2.30 mg/dL	Standard Deviation 0.382
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-2.77 mg/dL	Standard Deviation 0.623
Cohort 2: PF-06743649 5 mg	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-2.74 mg/dL	Standard Deviation 0.721
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 24 (n=6,2,0,6)	-0.20 mg/dL	Standard Deviation 0.834
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 4 (n=7,2,0,6)	-0.22 mg/dL	Standard Deviation 0.731
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 3 (n=7,3,10,9)	0.08 mg/dL	Standard Deviation 0.342
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Baseline (n=7,3,11,9)	9.28 mg/dL	Standard Deviation 0.954
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 8 (n=6,2,0,6)	-0.33 mg/dL	Standard Deviation 0.781
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 2 (n=7,2,0,6)	-0.05 mg/dL	Standard Deviation 0.797
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 12 (n=7,3,11,9)	-0.19 mg/dL	Standard Deviation 0.389
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 1 (n=6,3,11, 9)	0.11 mg/dL	Standard Deviation 0.19
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 8 (n=7,3,11,9)	-0.23 mg/dL	Standard Deviation 0.32
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 1 (n=7,2,0,6)	-0.03 mg/dL	Standard Deviation 0.787
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 4 (n=6,2,0,6)	-0.55 mg/dL	Standard Deviation 0.638
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 2 (n=7,3,11,9)	-0.02 mg/dL	Standard Deviation 0.156
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 2 (n=6,2,0,6)	-0.33 mg/dL	Standard Deviation 0.68
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Follow-up (Day 25-29) (n=6,3,10,9)	-0.30 mg/dL	Standard Deviation 1.648
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, pre-dose (n=7,2,0,6)	-0.07 mg/dL	Standard Deviation 0.734
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 11 (n=6,2,0,6)	-0.17 mg/dL	Standard Deviation 0.845
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 24 (n=7,2,0,6)	-0.17 mg/dL	Standard Deviation 0.794
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 12 (n=7,2,0,6)	-0.25 mg/dL	Standard Deviation 0.599
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 24 (n=7,3,11,9)	-0.18 mg/dL	Standard Deviation 0.396
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, pre-dose (n=6,2,0,6)	-0.22 mg/dL	Standard Deviation 0.747
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 1, Hour 4 (n=7,3,11,9)	-0.12 mg/dL	Standard Deviation 0.233
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 7, Hour 8 (n=7,2,0,6)	-0.38 mg/dL	Standard Deviation 0.578
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 12 (n=6,2,0,6)	-0.28 mg/dL	Standard Deviation 0.725
Cohort 1 and 2: Placebo	Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up	Day 14, Hour 1 (n=6,2,0,6)	-0.23 mg/dL	Standard Deviation 0.659

Comparison: Day 1, Hour 190% CI: [-0.55, -0.06]Mixed Models Analysis

Comparison: Day 1, Hour 290% CI: [-0.95, -0.28]Mixed Models Analysis

Comparison: Day 1, Hour 490% CI: [-1.52, -1.16]Mixed Models Analysis

Comparison: Day 1, Hour 890% CI: [-2.38, -1.33]Mixed Models Analysis

Comparison: Day 1, Hour 1290% CI: [-2.18, -1.48]Mixed Models Analysis

Comparison: Day 1, Hour 2490% CI: [-2.11, -1.37]Mixed Models Analysis

Comparison: Day 390% CI: [-2.89, -2.06]Mixed Models Analysis

Comparison: Day 7, pre-dose90% CI: [-3.29, -2.2]Mixed Models Analysis

Comparison: Day 7, Hour 190% CI: [-3.39, -2.21]Mixed Models Analysis

Comparison: Day 7, Hour 290% CI: [-3.72, -2.41]Mixed Models Analysis

Comparison: Day7, Hour 490% CI: [-4.03, -2.77]Mixed Models Analysis

Comparison: Day 7, Hour 890% CI: [-3.82, -2.79]Mixed Models Analysis

Comparison: Day 7, Hour 1290% CI: [-3.72, -2.68]Mixed Models Analysis

Comparison: Day 7, Hour 2490% CI: [-3.3, -2.32]Mixed Models Analysis

Comparison: Day 1190% CI: [-5.19, -3.92]Mixed Models Analysis

Comparison: Day 14, pre-dose90% CI: [-4.75, -3.88]Mixed Models Analysis

Comparison: Day 14, Hour 190% CI: [-5.02, -4.08]Mixed Models Analysis

Comparison: Day 14, Hour 290% CI: [-5.47, -4.47]Mixed Models Analysis

Comparison: Day 14, Hour 490% CI: [-5.83, -5.02]Mixed Models Analysis

Comparison: Day 14, Hour 890% CI: [-6.08, -5.05]Mixed Models Analysis

Comparison: Day 14, Hour 1290% CI: [-5.86, -4.82]Mixed Models Analysis

Comparison: Day 14, Hour 2490% CI: [-5.12, -4.18]Mixed Models Analysis

Comparison: Follow-up, Day 25-2990% CI: [-2.97, 0.79]Mixed Models Analysis

Comparison: Day 1, Hour 190% CI: [-0.92, -0.32]Mixed Models Analysis

Comparison: Day 1, Hour 290% CI: [-1.61, -0.75]Mixed Models Analysis

Comparison: Day 1, Hour 490% CI: [-3.14, -2.69]Mixed Models Analysis

Comparison: Day 1, Hour 890% CI: [-4.36, -3.03]Mixed Models Analysis

Comparison: Day 1, Hour 1290% CI: [-4.28, -3.4]Mixed Models Analysis

Comparison: Day 1, Hour 2490% CI: [-3.94, -3]Mixed Models Analysis

Comparison: Day 390% CI: [-5.29, -4.23]Mixed Models Analysis

Comparison: Day 7, pre-dose90% CI: [-6.62, -5]Mixed Models Analysis

Comparison: Day 7, Hour 190% CI: [-6.72, -4.95]Mixed Models Analysis

Comparison: Day 7, Hour 290% CI: [-7.17, -5.19]Mixed Models Analysis

Comparison: Day 7, Hour 490% CI: [-7.46, -5.55]Mixed Models Analysis

Comparison: Day 7, Hour 890% CI: [-7.07, -5.51]Mixed Models Analysis

Comparison: Day 7, Hour 1290% CI: [-7.03, -5.44]Mixed Models Analysis

Comparison: Day 7, Hour 2490% CI: [-6.5, -4.99]Mixed Models Analysis

Comparison: Day 1190% CI: [-6.59, -4.65]Mixed Models Analysis

Comparison: Day 14, pre-dose90% CI: [-6.42, -5.1]Mixed Models Analysis

Comparison: Day 14, Hour 190% CI: [-6.67, -5.24]Mixed Models Analysis

Comparison: Day 14, Hour 290% CI: [-6.9, -5.38]Mixed Models Analysis

Comparison: Day 14, Hour 490% CI: [-7.03, -5.81]Mixed Models Analysis

Comparison: Day 14, Hour 890% CI: [-7.41, -5.87]Mixed Models Analysis

Comparison: Day 14, Hour 1290% CI: [-7.18, -5.63]Mixed Models Analysis

Comparison: Day 14, Hour 2490% CI: [-6.47, -5.07]Mixed Models Analysis

Comparison: Follow-up, Day 25-2990% CI: [-4.96, -0.35]Mixed Models Analysis

Secondary

Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14

Change from baseline in urinary hypoxanthine cumulative amounts at Day 1, Day 7 and Day 14

Time frame: Baseline, Day 1, Day 7 and Day 14

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	5.999 mg	Standard Deviation 2.4371
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	2.435 mg	Standard Deviation 2.185
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	3.295 mg	Standard Deviation 3.1395
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	4.291 mg	Standard Deviation 3.2263
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	3.051 mg	Standard Deviation 2.5346
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	8.714 mg	Standard Deviation 0.2294
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	10.536 mg	Standard Deviation 0.9138
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	7.732 mg	Standard Deviation 1.5422
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	NA mg	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	1.600 mg	Standard Deviation 3.2414
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	NA mg	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	5.416 mg	Standard Deviation 2.3568
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	0.870 mg	Standard Deviation 0.8776
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	1.486 mg	Standard Deviation 2.123
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	5.500 mg	Standard Deviation 1.9022
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	0.384 mg	Standard Deviation 0.9645

Comparison: Day 190% CI: [-1.31, 3.1]Mixed Models Analysis

Comparison: Day 790% CI: [0.71, 5.11]Mixed Models Analysis

Comparison: Day 1490% CI: [1.33, 5.85]Mixed Models Analysis

Comparison: Day 190% CI: [-1.29, 4.31]Mixed Models Analysis

Comparison: Day 790% CI: [4.57, 10.89]Mixed Models Analysis

Comparison: Day 1490% CI: [5.91, 12.23]Mixed Models Analysis

Secondary

Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14

Change from baseline in urinary uric acid cumulative amounts.

Time frame: Baseline, Day 1, Day 7 and Day 14

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	658.495 mg	Standard Deviation 192.7457
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	308.363 mg	Standard Deviation 320.3229
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	38.603 mg	Standard Deviation 160.1758
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	55.610 mg	Standard Deviation 236.5787
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	424.684 mg	Standard Deviation 475.6851
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	-28.477 mg	Standard Deviation 235.27
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	-79.793 mg	Standard Deviation 195.2251
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	745.574 mg	Standard Deviation 262.1465
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	NA mg	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	168.996 mg	Standard Deviation 339.0577
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	NA mg	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	590.951 mg	Standard Deviation 195.9763
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	-34.863 mg	Standard Deviation 81.4321
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	-19.228 mg	Standard Deviation 117.268
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	583.854 mg	Standard Deviation 147.2471
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	-23.369 mg	Standard Deviation 141.1305

Comparison: Day 190% CI: [21.91, 611.88]Mixed Models Analysis

Comparison: Day 790% CI: [-94.87, 218.82]Mixed Models Analysis

Comparison: Day 1490% CI: [-71.2, 287.11]Mixed Models Analysis

Comparison: Day 190% CI: [58.3, 808.13]Mixed Models Analysis

Comparison: Day 790% CI: [-208.07, 234.47]Mixed Models Analysis

Comparison: Day 1490% CI: [-285.26, 225.6]Mixed Models Analysis

Secondary

Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14

Change from baseline in urinary xanthine cumulative amounts.

Time frame: Baseline, Day 1, Day 7 and Day 14

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	7.014 mg	Standard Deviation 1.9431
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	3.528 mg	Standard Deviation 2.6662
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	2.838 mg	Standard Deviation 1.8937
Cohort 1: PF-06743649 2.5 mg to 10 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	7.291 mg	Standard Deviation 2.1068
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	13.209 mg	Standard Deviation 4.89
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	27.886 mg	Standard Deviation 1.1209
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	29.063 mg	Standard Deviation 2.9613
Cohort 1: PF-06743649 40 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	8.783 mg	Standard Deviation 2.2772
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	NA mg	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	1.793 mg	Standard Deviation 2.2691
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	NA mg	—
Cohort 2: PF-06743649 5 mg	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	5.756 mg	Standard Deviation 2.3429
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 14 (n=6,2,0,6)	-0.708 mg	Standard Deviation 0.7644
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 1 (n=7,3,11,9)	0.031 mg	Standard Deviation 0.8807
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Baseline (n=7,3,11,9)	6.431 mg	Standard Deviation 2.4413
Cohort 1 and 2: Placebo	Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14	Change at Day 7 (n=7,2,0,6)	-0.832 mg	Standard Deviation 1.3666

Comparison: Day 190% CI: [0.71, 6.17]Mixed Models Analysis

Comparison: Day 790% CI: [1.97, 5.37]Mixed Models Analysis

Comparison: Day 1490% CI: [6.24, 9.96]Mixed Models Analysis

Comparison: Day 190% CI: [9.65, 16.59]Mixed Models Analysis

Comparison: Day 790% CI: [25.49, 30.49]Mixed Models Analysis

Comparison: Day 1490% CI: [26.14, 31.41]Mixed Models Analysis

Secondary

Duration of Gout Flare Attacks

Duration of gout flare attacks with participants who developed gout flare attacks.

Time frame: Baseline up to Day 42

Population: Participants who developed gout flare attacks (Duration was not assessed as no participant developed gout flare attacks).

Secondary

Incidence and Severity of Gout Flare Attacks

Time frame: Baseline up to Day 42

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment.

Arm	Measure	Value (NUMBER)
Cohort 1: PF-06743649 2.5 mg to 10 mg	Incidence and Severity of Gout Flare Attacks	0 participants
Cohort 1: PF-06743649 40 mg	Incidence and Severity of Gout Flare Attacks	0 participants
Cohort 2: PF-06743649 5 mg	Incidence and Severity of Gout Flare Attacks	0 participants
Cohort 1 and 2: Placebo	Incidence and Severity of Gout Flare Attacks	0 participants

Secondary

Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14

Number of participants reaching serum uric acid levels \<6, \<5 and \<4 mg/dL at 7 and 14 days after initiation.

Time frame: 24 hours post dose on Day 7 and Day 14

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment.

Arm	Measure	Group	Value (NUMBER)
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<6.0)	4 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<5.0)	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<4.0)	0 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<5.0)	6 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<4.0)	1 participants
Cohort 1: PF-06743649 2.5 mg to 10 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<6.0)	6 participants
Cohort 1: PF-06743649 40 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<5.0)	2 participants
Cohort 1: PF-06743649 40 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<6.0)	2 participants
Cohort 1: PF-06743649 40 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<6.0)	2 participants
Cohort 1: PF-06743649 40 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<4.0)	2 participants
Cohort 1: PF-06743649 40 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<5.0)	2 participants
Cohort 1: PF-06743649 40 mg	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<4.0)	2 participants
Cohort 1 and 2: Placebo	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<5.0)	0 participants
Cohort 1 and 2: Placebo	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<4.0)	0 participants
Cohort 1 and 2: Placebo	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<6.0)	0 participants
Cohort 1 and 2: Placebo	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 7 (<6.0)	0 participants
Cohort 1 and 2: Placebo	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<5.0)	0 participants
Cohort 1 and 2: Placebo	Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14	Day 14 (<4.0)	0 participants

Secondary

Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14

PF-06743648 is an active metabolite of PF-06743649. Data has been calculated by setting concentration values below the lower limit of quantification to zero. The lower limit of quantification was 2.00 nanograms per milliliter (ng/mL).

Time frame: Day 1, Day 7, and Day 14

Population: The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 0 (n=7,2,0)	7.259 ng/mL	Standard Deviation 3.5055
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 0 (n=7,3,11)	NA ng/mL	—
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 0 (n=6,2,0)	21.99 ng/mL	Standard Deviation 9.689
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 1 (n=7,2,0)	22.00 ng/mL	Standard Deviation 9.8895
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 4 (n=7,3,11)	30.07 ng/mL	Standard Deviation 7.3081
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 24 (n=7,2,0)	8.470 ng/mL	Standard Deviation 3.7998
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 2 (n=7,2,0)	42.83 ng/mL	Standard Deviation 20.763
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 24 (n=6,2,0)	27.32 ng/mL	Standard Deviation 14.608
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 12 (n=7,2,0)	16.67 ng/mL	Standard Deviation 5.5011
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 4 (n=7,2,0)	40.26 ng/mL	Standard Deviation 13.353
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 8 (n=6,2,0)	74.82 ng/mL	Standard Deviation 39.81
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 8 (n=7,2,0)	26.64 ng/mL	Standard Deviation 9.2428
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 8 (n=7,3,11)	18.09 ng/mL	Standard Deviation 5.4462
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 12 (n=6,2,0)	49.07 ng/mL	Standard Deviation 27.96
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 4 (n=6,2,0)	127.3 ng/mL	Standard Deviation 37.255
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 12 (n=7,3,11)	11.46 ng/mL	Standard Deviation 3.4996
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 2 (n=7,3,11)	28.69 ng/mL	Standard Deviation 14.265
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 2 (n=6,2,0)	139.3 ng/mL	Standard Deviation 53.432
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 24 (n=7,3,11)	6.059 ng/mL	Standard Deviation 2.8621
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 1 (n=7,3,11)	6.713 ng/mL	Standard Deviation 6.6738
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 1 (n=6,2,0)	74.72 ng/mL	Standard Deviation 37.91
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 8 (n=6,2,0)	280.5 ng/mL	Standard Deviation 9.1924
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 0 (n=7,3,11)	NA ng/mL	—
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 1 (n=7,3,11)	79.62 ng/mL	Standard Deviation 82.093
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 2 (n=7,3,11)	245.6 ng/mL	Standard Deviation 182.75
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 4 (n=7,3,11)	395.0 ng/mL	Standard Deviation 69.936
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 8 (n=7,3,11)	261.3 ng/mL	Standard Deviation 53.003
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 12 (n=7,3,11)	156.3 ng/mL	Standard Deviation 22.591
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 24 (n=7,3,11)	76.27 ng/mL	Standard Deviation 23.811
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 0 (n=7,2,0)	70.50 ng/mL	Standard Deviation 11.597
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 1 (n=7,2,0)	107.0 ng/mL	Standard Deviation 1.4142
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 2 (n=7,2,0)	344.0 ng/mL	Standard Deviation 49.497
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 4 (n=7,2,0)	397.0 ng/mL	Standard Deviation 9.8995
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 8 (n=7,2,0)	261.0 ng/mL	Standard Deviation 0
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 12 (n=7,2,0)	167.5 ng/mL	Standard Deviation 23.335
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 24 (n=7,2,0)	91.80 ng/mL	Standard Deviation 1.9799
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 0 (n=6,2,0)	76.60 ng/mL	Standard Deviation 9.4752
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 1 (n=6,2,0)	171.0 ng/mL	Standard Deviation 26.87
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 2 (n=6,2,0)	390.0 ng/mL	Standard Deviation 117.38
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 4 (n=6,2,0)	364.0 ng/mL	Standard Deviation 18.385
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 12 (n=6,2,0)	162.0 ng/mL	Standard Deviation 1.4142
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 24 (n=6,2,0)	81.35 ng/mL	Standard Deviation 1.2021
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 0 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 1 (n=7,3,11)	13.81 ng/mL	Standard Deviation 10.519
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 0 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 24 (n=7,3,11)	12.76 ng/mL	Standard Deviation 7.3997
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 24 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 1 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 12 (n=7,3,11)	25.67 ng/mL	Standard Deviation 13.251
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 12 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 2 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 8 (n=7,3,11)	38.25 ng/mL	Standard Deviation 18.527
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 0 (n=7,3,11)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 4 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 4 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 4 (n=7,3,11)	59.21 ng/mL	Standard Deviation 29.231
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 8 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 2 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 2 (n=7,3,11)	49.30 ng/mL	Standard Deviation 26.599
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 12 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 1 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 8 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 24 (n=7,2,0)	NA ng/mL	—

Secondary

Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14

Data has been calculated by setting concentration values below the lower limit of quantification to zero. The lower limit of quantification was 10.0 nanograms per milliliter (ng/mL).

Time frame: 0, 1, 2, 4, 8, 12 and 24 hours at Day 1, Day 7, and Day 14

Population: All participants randomized and treated who have at least 1 measureable concentration; n=number of participants analyzed in each respective arm.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 0 (n=7,2,0)	10.50 ng/mL	Standard Deviation 10.56
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 0 (n=7,3,11)	NA ng/mL	—
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 0 (n=6,2,0)	47.08 ng/mL	Standard Deviation 27.363
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 1 (n=7,2,0)	185.9 ng/mL	Standard Deviation 102.26
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 4 (n=7,3,11)	105.8 ng/mL	Standard Deviation 34.342
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 24 (n=7,2,0)	12.50 ng/mL	Standard Deviation 10.356
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 2 (n=7,2,0)	211.7 ng/mL	Standard Deviation 95.552
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 24 (n=6,2,0)	54.27 ng/mL	Standard Deviation 34.849
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 12 (n=7,2,0)	42.30 ng/mL	Standard Deviation 16.272
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 4 (n=7,2,0)	137.3 ng/mL	Standard Deviation 43.222
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 8 (n=6,2,0)	245.8 ng/mL	Standard Deviation 99.385
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 8 (n=7,2,0)	67.59 ng/mL	Standard Deviation 19.509
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 8 (n=7,3,11)	47.27 ng/mL	Standard Deviation 19.596
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 12 (n=6,2,0)	163.3 ng/mL	Standard Deviation 73.48
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 4 (n=6,2,0)	429.5 ng/mL	Standard Deviation 165.51
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 12 (n=7,3,11)	26.84 ng/mL	Standard Deviation 13.738
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 2 (n=7,3,11)	196.6 ng/mL	Standard Deviation 47.367
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 2 (n=6,2,0)	729.5 ng/mL	Standard Deviation 218.79
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 24 (n=7,3,11)	7.586 ng/mL	Standard Deviation 10.183
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 1 (n=7,3,11)	163.8 ng/mL	Standard Deviation 84.336
Cohort 1: PF-06743649 2.5 mg to 10 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 1 (n=6,2,0)	736.7 ng/mL	Standard Deviation 483.18
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 8 (n=6,2,0)	687.0 ng/mL	Standard Deviation 96.167
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 0 (n=7,3,11)	NA ng/mL	—
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 1 (n=7,3,11)	1097 ng/mL	Standard Deviation 1011.8
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 2 (n=7,3,11)	1570 ng/mL	Standard Deviation 416.77
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 4 (n=7,3,11)	1081 ng/mL	Standard Deviation 189.22
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 8 (n=7,3,11)	523.3 ng/mL	Standard Deviation 108.89
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 12 (n=7,3,11)	229.3 ng/mL	Standard Deviation 36.665
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 24 (n=7,3,11)	86.67 ng/mL	Standard Deviation 18.434
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 0 (n=7,2,0)	154.0 ng/mL	Standard Deviation 41.012
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 1 (n=7,2,0)	1275 ng/mL	Standard Deviation 261.63
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 2 (n=7,2,0)	2715 ng/mL	Standard Deviation 487.9
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 4 (n=7,2,0)	1520 ng/mL	Standard Deviation 183.85
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 8 (n=7,2,0)	697.0 ng/mL	Standard Deviation 49.497
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 12 (n=7,2,0)	457.5 ng/mL	Standard Deviation 78.489
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 24 (n=7,2,0)	147.0 ng/mL	Standard Deviation 31.113
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 0 (n=6,2,0)	157.5 ng/mL	Standard Deviation 43.134
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 1 (n=6,2,0)	1995 ng/mL	Standard Deviation 417.19
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 2 (n=6,2,0)	2140 ng/mL	Standard Deviation 325.27
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 4 (n=6,2,0)	1480 ng/mL	Standard Deviation 325.27
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 12 (n=6,2,0)	400.0 ng/mL	Standard Deviation 74.953
Cohort 1: PF-06743649 40 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 24 (n=6,2,0)	133.5 ng/mL	Standard Deviation 13.435
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 0 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 1 (n=7,3,11)	371.3 ng/mL	Standard Deviation 239.52
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 0 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 24 (n=7,3,11)	48.90 ng/mL	Standard Deviation 49.583
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 24 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 1 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 12 (n=7,3,11)	99.27 ng/mL	Standard Deviation 70.301
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 12 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 2 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 8 (n=7,3,11)	142.7 ng/mL	Standard Deviation 87.111
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 0 (n=7,3,11)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 4 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 4 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 4 (n=7,3,11)	282.4 ng/mL	Standard Deviation 106.48
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 8 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 2 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 1, Hour 2 (n=7,3,11)	454.7 ng/mL	Standard Deviation 141.62
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 12 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 1 (n=7,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 14, Hour 8 (n=6,2,0)	NA ng/mL	—
Cohort 2: PF-06743649 5 mg	Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14	Day 7, Hour 24 (n=7,2,0)	NA ng/mL	—

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Efficacy, Safety And Tolerability Of PF-06743649 In Gout Subjects.

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Baseline of Serum Uric Acid

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

Number of Participants With Laboratory Test Abnormalities

Number of Participants With Potentially Clinically Significant Vital Signs Findings

Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14

Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up

Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up

Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up

Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14

Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14

Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14

Duration of Gout Flare Attacks

Incidence and Severity of Gout Flare Attacks

Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14

Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14

Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14