Back to resultsEfficacy, Safety And Tolerability Of PF-06743649 In Gout Subjects.
Primary Purpose
Gout
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-06743649
Placebo
PF-06743649
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Gout focused on measuring Hyperuricemia, gout, serum uric acid
Eligibility Criteria
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.
Sites / Locations
- MRA Clinical Research, LLC
- Miami Research Associates, Inc.
- Vince and Associates Clinical Research Inc.
- Vince and Associates Clinical Research, Inc.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
PF-06743649 dose level 1 (Cohort 1)
Placebo for PF-06743649 (Cohort 1)
PF-06743649 dose level 2 (Cohort 2)
Placebo for PF-06743649 (Cohort 2)
Arm Description
Outcomes
Primary Outcome Measures
Baseline of Serum Uric Acid
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
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.
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).
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).
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.
Secondary Outcome Measures
Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up
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.
Incidence and Severity of Gout Flare Attacks
Duration of Gout Flare Attacks
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
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
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
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
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.
Change From Baseline in Urinary Xanthine Levels at 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
Change from baseline in urinary hypoxanthine cumulative amounts at Day 1, Day 7 and Day 14
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02187029
Brief Title
Efficacy, Safety And Tolerability Of PF-06743649 In Gout Subjects.
Official Title
A Randomized, Double Blind, Third Party Open, Placebo Controlled Multi-center Study Of Efficacy, Safety And Tolerability Of Pf-06743649 In Gout Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
B7911002 was prematurely discontinued due to a safety concern that led to decision to terminate the study on 10 Nov 2014
Study Start Date
July 2014 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gout
Keywords
Hyperuricemia, gout, serum uric acid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-06743649 dose level 1 (Cohort 1)
Arm Type
Experimental
Arm Title
Placebo for PF-06743649 (Cohort 1)
Arm Type
Placebo Comparator
Arm Title
PF-06743649 dose level 2 (Cohort 2)
Arm Type
Experimental
Arm Title
Placebo for PF-06743649 (Cohort 2)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
PF-06743649
Intervention Description
Daily dosing (dose level 1) tablet for 14 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Daily dosing (tablet) for 14 days
Intervention Type
Drug
Intervention Name(s)
PF-06743649
Intervention Description
Daily dosing (dose level 2) tablet(s) for 14 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Daily dosing (tablets) for 14 days
Primary Outcome Measure Information:
Title
Baseline of Serum Uric Acid
Description
An elevation in serum uric acid, hyperuricemia, is a prerequisite for the development of gout.
Time Frame
Baseline (pre-dose Day 1)
Title
Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14
Time Frame
Day 14 Hour 24
Title
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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)
Title
Number of Participants With Laboratory Test Abnormalities
Description
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)
Title
Number of Participants With Potentially Clinically Significant Vital Signs Findings
Description
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)
Title
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria
Description
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
Secondary Outcome Measure Information:
Title
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)
Title
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
Description
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
Title
Incidence and Severity of Gout Flare Attacks
Time Frame
Baseline up to Day 42
Title
Duration of Gout Flare Attacks
Description
Duration of gout flare attacks with participants who developed gout flare attacks.
Time Frame
Baseline up to Day 42
Title
Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14
Description
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
Title
Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14
Description
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
Title
Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up
Description
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)
Title
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)
Title
Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14
Description
Change from baseline in urinary uric acid cumulative amounts.
Time Frame
Baseline, Day 1, Day 7 and Day 14
Title
Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14
Description
Change from baseline in urinary xanthine cumulative amounts.
Time Frame
Baseline, Day 1, Day 7 and Day 14
Title
Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
MRA Clinical Research, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Miami Research Associates, Inc.
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Vince and Associates Clinical Research Inc.
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States
Facility Name
Vince and Associates Clinical Research, Inc.
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B7911002&StudyName=Efficacy%2C%20Safety%20And%20Tolerability%20Of%20PF-06743649%20In%20Gout%20Subjects.%0A
Description
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Efficacy, Safety And Tolerability Of PF-06743649 In Gout Subjects.
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