Trial Outcomes & Findings for Efficacy, Safety And Tolerability Of PF-06743649 In Gout Subjects. (NCT NCT02187029)

NCT ID: NCT02187029

Last Updated: 2016-11-11

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

Baseline (pre-dose Day 1)

Results posted on

2016-11-11

Participant Flow

Participant milestones

Participant milestones
Measure	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.	Cohort 1: PF-06743649 40 mg Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	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.	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.
Overall Study STARTED	7	3	11	9
Overall Study COMPLETED	6	2	0	6
Overall Study NOT COMPLETED	1	1	11	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Cohort 1: PF-06743649 40 mg Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	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.	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.
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

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.	Total n=30 Participants Total of all reporting groups
Age, Continuous	47.1 years STANDARD_DEVIATION 8.1 • n=5 Participants	50.7 years STANDARD_DEVIATION 9.7 • n=7 Participants	43.4 years STANDARD_DEVIATION 9.8 • n=5 Participants	46.8 years STANDARD_DEVIATION 9.3 • n=4 Participants	46.0 years STANDARD_DEVIATION 9.1 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants	9 Participants n=4 Participants	30 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (pre-dose Day 1)

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

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

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
Baseline of Serum Uric Acid	8.800 milligram per deciliter(mg/dL) Standard Deviation 1.1402	9.100 milligram per deciliter(mg/dL) Standard Deviation 0.8185	8.991 milligram per deciliter(mg/dL) Standard Deviation 0.6549	9.278 milligram per deciliter(mg/dL) Standard Deviation 0.9536

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=6 Participants 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.	Cohort 1: PF-06743649 40 mg n=2 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	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.	Cohort 1 and 2: Placebo n=6 Participants 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.
Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14	-52.891 percent (%) Standard Deviation 6.1661	-67.480 percent (%) Standard Deviation 1.1498	—	-1.381 percent (%) Standard Deviation 9.1430

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Participants with SAEs	0 participants	0 participants	1 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Participants with AEs	2 participants	3 participants	3 participants	4 participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
Number of Participants With Laboratory Test Abnormalities	1 participants	1 participants	3 participants	2 participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
Number of Participants With Potentially Clinically Significant Vital Signs Findings Decrease Supine Diastolic BP (mmHg) >=20	0 participants	0 participants	1 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine Systolic BP (mmHg) <90	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine Diastolic BP (mmHg) <50	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine Pulse Rate (bpm) <40	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine Pulse Rate (bpm) >120	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Increase Supine Systolic BP (mmHg) >=30	1 participants	0 participants	1 participants	1 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Increase Supine Diastolic BP (mmHg) >=20	1 participants	0 participants	1 participants	1 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Decrease Supine Systolic BP (mmHg) >=30	0 participants	0 participants	1 participants	0 participants

PRIMARY outcome

Timeframe: Baseline up to Day 16

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

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.

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria QRS complex (msec) >=140	0 participants	0 participants	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria PR increase from baseline >=25/50%	0 participants	0 participants	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria QTCF (msec) 450-<480	0 participants	0 participants	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria PR (msec) >=300	0 participants	0 participants	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria QTCF (msec) 480-<500	0 participants	0 participants	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria QTCF (msec) >=500	0 participants	0 participants	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria QRS complex increase from baseline >=50%	0 participants	0 participants	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria QTCF increase from baseline 30 to <60 msec	0 participants	0 participants	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria QTCF increase from baseline >=60 msec	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
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 1.140	9.10 mg/dL Standard Deviation 0.819	8.99 mg/dL Standard Deviation 0.655	9.28 mg/dL Standard Deviation 0.954
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	-0.50 mg/dL Standard Deviation 0.436	-0.51 mg/dL Standard Deviation 0.353	0.11 mg/dL Standard Deviation 0.190
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	-1.17 mg/dL Standard Deviation 0.839	-1.27 mg/dL Standard Deviation 0.403	-0.02 mg/dL Standard Deviation 0.156
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	-3.07 mg/dL Standard Deviation 0.115	-2.30 mg/dL Standard Deviation 0.382	-0.12 mg/dL Standard Deviation 0.233
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	-3.87 mg/dL Standard Deviation 0.473	-2.77 mg/dL Standard Deviation 0.623	-0.23 mg/dL Standard Deviation 0.320
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	-3.83 mg/dL Standard Deviation 0.577	-2.74 mg/dL Standard Deviation 0.721	-0.19 mg/dL Standard Deviation 0.389
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	-3.43 mg/dL Standard Deviation 0.757	-2.04 mg/dL Standard Deviation 0.770	-0.18 mg/dL Standard Deviation 0.396
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	-4.50 mg/dL Standard Deviation 0.529	-3.02 mg/dL Standard Deviation 0.925	0.08 mg/dL Standard Deviation 0.342
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	-5.75 mg/dL Standard Deviation 0.212	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.07 mg/dL Standard Deviation 0.734
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	-5.75 mg/dL Standard Deviation 0.212	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.03 mg/dL Standard Deviation 0.787
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	-6.10 mg/dL Standard Deviation 0.283	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.05 mg/dL Standard Deviation 0.797
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	-6.60 mg/dL Standard Deviation 0.283	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.22 mg/dL Standard Deviation 0.731
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	-6.60 mg/dL Standard Deviation 0.141	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.38 mg/dL Standard Deviation 0.578
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	-6.45 mg/dL Standard Deviation 0.071	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.25 mg/dL Standard Deviation 0.599
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	-5.90 mg/dL Standard Deviation 0.141	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.17 mg/dL Standard Deviation 0.794
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	-5.75 mg/dL Standard Deviation 0.071	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.17 mg/dL Standard Deviation 0.845
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 0.900	-5.75 mg/dL Standard Deviation 0.636	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.22 mg/dL Standard Deviation 0.747
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	-6.05 mg/dL Standard Deviation 0.495	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.23 mg/dL Standard Deviation 0.659
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	-6.35 mg/dL Standard Deviation 0.495	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.33 mg/dL Standard Deviation 0.680
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	-6.80 mg/dL Standard Deviation 0.566	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.55 mg/dL Standard Deviation 0.638
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	-6.85 mg/dL Standard Deviation 0.636	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.33 mg/dL Standard Deviation 0.781
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	-6.60 mg/dL Standard Deviation 0.566	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.28 mg/dL Standard Deviation 0.725
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 0.940	-5.90 mg/dL Standard Deviation 0.424	NA mg/dL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.20 mg/dL Standard Deviation 0.834
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	-2.27 mg/dL Standard Deviation 2.593	0.45 mg/dL Standard Deviation 0.938	-0.30 mg/dL Standard Deviation 1.648

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	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.	Cohort 1 and 2: Placebo n=9 Participants 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.
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	2 participants	—	0 participants
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	2 participants	—	0 participants
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	2 participants	—	0 participants
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	2 participants	—	0 participants
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	2 participants	—	0 participants
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	2 participants	—	0 participants

SECONDARY outcome

Timeframe: Baseline up to Day 42

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

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
Incidence and Severity of Gout Flare Attacks	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline up to Day 42

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	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.
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 Standard Deviation NA Data was not reported because the observations were not above lower limit of quantification.	NA ng/mL Standard Deviation NA Data was not reported because the observations were not above lower limit of quantification.	NA ng/mL Standard Deviation NA Data was not reported because the observations were not above lower limit of quantification.	—
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	1097 ng/mL Standard Deviation 1011.8	371.3 ng/mL Standard Deviation 239.52	—
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	1570 ng/mL Standard Deviation 416.77	454.7 ng/mL Standard Deviation 141.62	—
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	1081 ng/mL Standard Deviation 189.22	282.4 ng/mL Standard Deviation 106.48	—
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	523.3 ng/mL Standard Deviation 108.89	142.7 ng/mL Standard Deviation 87.111	—
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	229.3 ng/mL Standard Deviation 36.665	99.27 ng/mL Standard Deviation 70.301	—
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	86.67 ng/mL Standard Deviation 18.434	48.90 ng/mL Standard Deviation 49.583	—
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 10.560	154.0 ng/mL Standard Deviation 41.012	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	1275 ng/mL Standard Deviation 261.63	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	2715 ng/mL Standard Deviation 487.90	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	1520 ng/mL Standard Deviation 183.85	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	697.0 ng/mL Standard Deviation 49.497	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	457.5 ng/mL Standard Deviation 78.489	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	147.0 ng/mL Standard Deviation 31.113	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	157.5 ng/mL Standard Deviation 43.134	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	1995 ng/mL Standard Deviation 417.19	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	2140 ng/mL Standard Deviation 325.27	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	1480 ng/mL Standard Deviation 325.27	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	687.0 ng/mL Standard Deviation 96.167	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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 73.480	400.0 ng/mL Standard Deviation 74.953	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	133.5 ng/mL Standard Deviation 13.435	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	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.
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 Standard Deviation NA Data was not reported because the observations were not above lower limit of quantification.	NA ng/mL Standard Deviation NA Data was not reported because the observations were not above lower limit of quantification.	NA ng/mL Standard Deviation NA Data was not reported because the observations were not above lower limit of quantification.	—
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	79.62 ng/mL Standard Deviation 82.093	13.81 ng/mL Standard Deviation 10.519	—
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	245.6 ng/mL Standard Deviation 182.75	49.30 ng/mL Standard Deviation 26.599	—
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	395.0 ng/mL Standard Deviation 69.936	59.21 ng/mL Standard Deviation 29.231	—
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	261.3 ng/mL Standard Deviation 53.003	38.25 ng/mL Standard Deviation 18.527	—
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	156.3 ng/mL Standard Deviation 22.591	25.67 ng/mL Standard Deviation 13.251	—
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	76.27 ng/mL Standard Deviation 23.811	12.76 ng/mL Standard Deviation 7.3997	—
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	70.50 ng/mL Standard Deviation 11.597	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	107.0 ng/mL Standard Deviation 1.4142	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	344.0 ng/mL Standard Deviation 49.497	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	397.0 ng/mL Standard Deviation 9.8995	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	261.0 ng/mL Standard Deviation 0.00000	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	167.5 ng/mL Standard Deviation 23.335	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	91.80 ng/mL Standard Deviation 1.9799	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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 9.6890	76.60 ng/mL Standard Deviation 9.4752	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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 37.910	171.0 ng/mL Standard Deviation 26.870	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	390.0 ng/mL Standard Deviation 117.38	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	364.0 ng/mL Standard Deviation 18.385	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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 39.810	280.5 ng/mL Standard Deviation 9.1924	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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 27.960	162.0 ng/mL Standard Deviation 1.4142	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—
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	81.35 ng/mL Standard Deviation 1.2021	NA ng/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
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 0.15380	1.0060 mcg/mL Standard Deviation 0.41079	0.8677 mcg/mL Standard Deviation 0.18896	0.8922 mcg/mL Standard Deviation 0.13486
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	0.1440 mcg/mL Standard Deviation 0.56564	-0.1205 mcg/mL Standard Deviation 0.16427	0.0847 mcg/mL Standard Deviation 0.41097
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	0.2130 mcg/mL Standard Deviation 0.40812	-0.0145 mcg/mL Standard Deviation 0.13714	-0.0421 mcg/mL Standard Deviation 0.21113
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	0.0717 mcg/mL Standard Deviation 0.62608	-0.1426 mcg/mL Standard Deviation 0.14932	-0.0369 mcg/mL Standard Deviation 0.32185
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	0.1760 mcg/mL Standard Deviation 0.78402	-0.1895 mcg/mL Standard Deviation 0.18641	-0.1870 mcg/mL Standard Deviation 0.26137
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	0.2703 mcg/mL Standard Deviation 0.62935	-0.0979 mcg/mL Standard Deviation 0.15883	-0.0967 mcg/mL Standard Deviation 0.22579
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	0.5607 mcg/mL Standard Deviation 0.66507	-0.0039 mcg/mL Standard Deviation 0.10751	0.1200 mcg/mL Standard Deviation 0.48900
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	0.0810 mcg/mL Standard Deviation 0.21355	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.1317 mcg/mL Standard Deviation 0.57974
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	-0.1575 mcg/mL Standard Deviation 0.46598	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0285 mcg/mL Standard Deviation 0.43096
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	0.1360 mcg/mL Standard Deviation 0.67317	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0103 mcg/mL Standard Deviation 0.35162
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	-0.2505 mcg/mL Standard Deviation 0.37406	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.0762 mcg/mL Standard Deviation 0.37371
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	-0.0495 mcg/mL Standard Deviation 0.61023	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0543 mcg/mL Standard Deviation 0.35172
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	-0.5290 mcg/mL Standard Deviation 0.32951	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.1557 mcg/mL Standard Deviation 0.15279
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	0.1410 mcg/mL Standard Deviation 0.68024	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0680 mcg/mL Standard Deviation 0.35421
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	0.0710 mcg/mL Standard Deviation 0.24183	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0978 mcg/mL Standard Deviation 0.10319
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	0.1660 mcg/mL Standard Deviation 0.30547	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.1065 mcg/mL Standard Deviation 0.19276
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 0.20110	0.2860 mcg/mL Standard Deviation 0.29133	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.0047 mcg/mL Standard Deviation 0.25228
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	0.1210 mcg/mL Standard Deviation 0.42568	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.0133 mcg/mL Standard Deviation 0.30407
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 0.32120	-0.2310 mcg/mL Standard Deviation 0.16829	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0698 mcg/mL Standard Deviation 0.34513
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	0.0510 mcg/mL Standard Deviation 0.11455	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.1075 mcg/mL Standard Deviation 0.20019
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	0.2260 mcg/mL Standard Deviation 0.36204	NA mcg/mL Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.0855 mcg/mL Standard Deviation 0.36310
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	-0.2550 mcg/mL Standard Deviation 0.91149	0.3204 mcg/mL Standard Deviation 0.30373	0.3778 mcg/mL Standard Deviation 0.73741

SECONDARY outcome

Timeframe: 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.

Change from baseline in urinary uric acid cumulative amounts.

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
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	745.574 mg Standard Deviation 262.1465	590.951 mg Standard Deviation 195.9763	583.854 mg Standard Deviation 147.2471
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	424.684 mg Standard Deviation 475.6851	168.996 mg Standard Deviation 339.0577	-19.228 mg Standard Deviation 117.2680
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	-28.477 mg Standard Deviation 235.2700	NA mg Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-23.369 mg Standard Deviation 141.1305
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	-79.793 mg Standard Deviation 195.2251	NA mg Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-34.863 mg Standard Deviation 81.4321

SECONDARY outcome

Timeframe: 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.

Change from baseline in urinary xanthine cumulative amounts.

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
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	8.783 mg Standard Deviation 2.2772	5.756 mg Standard Deviation 2.3429	6.431 mg Standard Deviation 2.4413
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	13.209 mg Standard Deviation 4.8900	1.793 mg Standard Deviation 2.2691	0.031 mg Standard Deviation 0.8807
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	27.886 mg Standard Deviation 1.1209	NA mg Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.832 mg Standard Deviation 1.3666
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	29.063 mg Standard Deviation 2.9613	NA mg Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.708 mg Standard Deviation 0.7644

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
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	7.732 mg Standard Deviation 1.5422	5.416 mg Standard Deviation 2.3568	5.500 mg Standard Deviation 1.9022
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 2.1850 • Interval 0.94 to 3.93	3.051 mg Standard Deviation 2.5346 • Interval 0.76 to 5.34	1.600 mg Standard Deviation 3.2414	1.486 mg Standard Deviation 2.1230 • Interval -0.08 to 3.16
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 • Interval 1.8 to 4.79	8.714 mg Standard Deviation 0.2294 • Interval 5.4 to 10.83	NA mg Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.384 mg Standard Deviation 0.9645 • Interval -1.23 to 2.0
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 • Interval 2.88 to 6.05	10.536 mg Standard Deviation 0.9138 • Interval 7.22 to 12.66	NA mg Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.870 mg Standard Deviation 0.8776 • Interval -0.75 to 2.49

Adverse Events

Cohort 1: PF-06743649 2.5 mg to 10 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 1: PF-06743649 40 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 2: PF-06743649 5 mg

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 1 and 2: Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 participants at risk 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.	Cohort 1: PF-06743649 40 mg n=3 participants at risk Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 participants at risk 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.	Cohort 1 and 2: Placebo n=9 participants at risk 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.
Renal and urinary disorders Renal injury	0.00% 0/7 • Baseline up to 28 days after last study drug administration. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another, or 1 participant may have experienced both an AE and SAE during the study. All treated participants were included in the analysis.	0.00% 0/3 • Baseline up to 28 days after last study drug administration. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another, or 1 participant may have experienced both an AE and SAE during the study. All treated participants were included in the analysis.	9.1% 1/11 • Baseline up to 28 days after last study drug administration. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another, or 1 participant may have experienced both an AE and SAE during the study. All treated participants were included in the analysis.	0.00% 0/9 • Baseline up to 28 days after last study drug administration. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another, or 1 participant may have experienced both an AE and SAE during the study. All treated participants were included in the analysis.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cohort 1: PF-06743649 2.5 mg to 10 mg n=7 Participants 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.	Cohort 1: PF-06743649 40 mg n=3 Participants Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.	Cohort 2: PF-06743649 5 mg n=11 Participants 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.	Cohort 1 and 2: Placebo n=9 Participants 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.
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	0.8263 micrograms per milliliter (mcg/mL) Standard Deviation 0.77448	0.1161 micrograms per milliliter (mcg/mL) Standard Deviation 0.18229	0.2299 micrograms per milliliter (mcg/mL) Standard Deviation 0.44888
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 0.09010	0.5960 micrograms per milliliter (mcg/mL) Standard Deviation 0.01131	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.0330 micrograms per milliliter (mcg/mL) Standard Deviation 0.09579
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	0.5595 micrograms per milliliter (mcg/mL) Standard Deviation 0.00212	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0210 micrograms per milliliter (mcg/mL) Standard Deviation 0.07869
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	0.2030 micrograms per milliliter (mcg/mL) Standard Deviation 0.11738	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0778 micrograms per milliliter (mcg/mL) Standard Deviation 0.06107
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	0.2680 micrograms per milliliter (mcg/mL) Standard Deviation 0.10095	0.2102 micrograms per milliliter (mcg/mL) Standard Deviation 0.04037	0.2257 micrograms per milliliter (mcg/mL) Standard Deviation 0.05304
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	0.1057 micrograms per milliliter (mcg/mL) Standard Deviation 0.02155	-0.0192 micrograms per milliliter (mcg/mL) Standard Deviation 0.04214	-0.0112 micrograms per milliliter (mcg/mL) Standard Deviation 0.08230
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	0.3667 micrograms per milliliter (mcg/mL) Standard Deviation 0.27216	0.0346 micrograms per milliliter (mcg/mL) Standard Deviation 0.05090	-0.0220 micrograms per milliliter (mcg/mL) Standard Deviation 0.03653
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	0.3317 micrograms per milliliter (mcg/mL) Standard Deviation 0.11558	-0.0306 micrograms per milliliter (mcg/mL) Standard Deviation 0.05783	-0.0511 micrograms per milliliter (mcg/mL) Standard Deviation 0.06510
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	0.1947 micrograms per milliliter (mcg/mL) Standard Deviation 0.14431	-0.0918 micrograms per milliliter (mcg/mL) Standard Deviation 0.02295	-0.0982 micrograms per milliliter (mcg/mL) Standard Deviation 0.3674
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 0.04270	0.0847 micrograms per milliliter (mcg/mL) Standard Deviation 0.11634	-0.0921 micrograms per milliliter (mcg/mL) Standard Deviation 0.03801	-0.0786 micrograms per milliliter (mcg/mL) Standard Deviation 0.05731
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	0.1927 micrograms per milliliter (mcg/mL) Standard Deviation 0.04879	0.0140 micrograms per milliliter (mcg/mL) Standard Deviation 0.03411	0.0233 micrograms per milliliter (mcg/mL) Standard Deviation 0.10687
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	0.1450 micrograms per milliliter (mcg/mL) Standard Deviation 0.00283	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.0177 micrograms per milliliter (mcg/mL) Standard Deviation 0.13598
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	0.1765 micrograms per milliliter (mcg/mL) Standard Deviation 0.07566	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0170 micrograms per milliliter (mcg/mL) Standard Deviation 0.07475
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 0.05070	0.5300 micrograms per milliliter (mcg/mL) Standard Deviation 0.21779	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0098 micrograms per milliliter (mcg/mL) Standard Deviation 0.08066
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	0.4995 micrograms per milliliter (mcg/mL) Standard Deviation 0.14920	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0233 micrograms per milliliter (mcg/mL) Standard Deviation 0.07942
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	0.3010 micrograms per milliliter (mcg/mL) Standard Deviation 0.14425	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0843 micrograms per milliliter (mcg/mL) Standard Deviation 0.05064
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	-0.0535 micrograms per milliliter (mcg/mL) Standard Deviation 0.01909	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0750 micrograms per milliliter (mcg/mL) Standard Deviation 0.04685
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	0.1465 micrograms per milliliter (mcg/mL) Standard Deviation 0.07990	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0242 micrograms per milliliter (mcg/mL) Standard Deviation 0.06072
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	0.1540 micrograms per milliliter (mcg/mL) Standard Deviation 0.07778	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0120 micrograms per milliliter (mcg/mL) Standard Deviation 0.02367
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	0.3515 micrograms per milliliter (mcg/mL) Standard Deviation 0.10819	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0008 micrograms per milliliter (mcg/mL) Standard Deviation 0.02699
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	0.1175 micrograms per milliliter (mcg/mL) Standard Deviation 0.18031	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	-0.0801 micrograms per milliliter (mcg/mL) Standard Deviation 0.04477
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	0.1695 micrograms per milliliter (mcg/mL) Standard Deviation 0.08132	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data due to cohort termination after 2 days of dosing.	0.0242 micrograms per milliliter (mcg/mL) Standard Deviation 0.06158