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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
30
Daily dosing (dose level 1) tablet for 14 days
Daily dosing (tablet) for 14 days
Daily dosing (dose level 2) tablet(s) for 14 days
MRA Clinical Research, LLC
Miami, Florida, United States
Miami Research Associates, Inc.
South Miami, Florida, United States
Vince and Associates Clinical Research Inc.
Overland Park, Kansas, United States
Vince and Associates Clinical Research, Inc.
Overland Park, Kansas, United States
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)
Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14
Time frame: Day 14 Hour 24
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)
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).
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Daily dosing (tablets) for 14 days
Time frame: Baseline up to follow up visit (Day 25-29)
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)
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
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)
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
Incidence and Severity of Gout Flare Attacks
Time frame: Baseline up to Day 42
Duration of Gout Flare Attacks
Duration of gout flare attacks with participants who developed gout flare attacks.
Time frame: Baseline up to Day 42
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
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
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)
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)
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
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
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