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

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ClinicalTrials.gov Identifier: NCT02187029
Recruitment Status : Terminated (B7911002 was prematurely discontinued due to a safety concern that led to decision to terminate the study on 10 Nov 2014)
First Posted : July 10, 2014
Results First Posted : November 11, 2016
Last Update Posted : November 11, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Gout Drug: PF-06743649 Other: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : July 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Gout
MedlinePlus related topics: Gout

Arm Intervention/treatment
Experimental: PF-06743649 dose level 1 (Cohort 1) Drug: PF-06743649
Daily dosing (dose level 1) tablet for 14 days

Placebo Comparator: Placebo for PF-06743649 (Cohort 1) Other: Placebo
Daily dosing (tablet) for 14 days

Experimental: PF-06743649 dose level 2 (Cohort 2) Drug: PF-06743649
Daily dosing (dose level 2) tablet(s) for 14 days

Placebo Comparator: Placebo for PF-06743649 (Cohort 2) Other: Placebo
Daily dosing (tablets) for 14 days




Primary Outcome Measures :
  1. Baseline of Serum Uric Acid [ Time Frame: Baseline (pre-dose Day 1) ]
    An elevation in serum uric acid, hyperuricemia, is a prerequisite for the development of gout.

  2. Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14 [ Time Frame: Day 14 Hour 24 ]
  3. Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last study drug administration (Day 42) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state AEs included both serious and non-serious events.

  4. Number of Participants With Laboratory Test Abnormalities [ Time Frame: Baseline up to follow up visit (Day 25-29) ]
    Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters include hematology (Hemoglobin, Hematocrit, red blood cell [RBC] count, Platelet count, mean corpuscular volume [MCV], mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration [MCHC], white blood cell [WBC] count, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes), hematocrit (blood urea nitrogen [BUN]/urea and Creatinine, Glucose , Calcium, Sodium, Potassium, Chloride, Total CO2 [Bicarbonate], aspartate transaminase [AST], alanine transaminase [ALT], Total Bilirubin, Alkaline phosphatase, Albumin, Total protein, Thyroid Stimulating Hormone [TSH], free T3 [FT3] and free T4 [FT4] ), urinalysis (pH, Glucose [qual], Protein, Blood, Ketones, Nitrites, Leukocyte esterase, Urobilinogen, Urine bilirubin, Microscopy [including crystals]) and other (follicle-stimulating hormone [FSH], Urine drug screen).

  5. Number of Participants With Potentially Clinically Significant Vital Signs Findings [ Time Frame: Baseline up to follow up visit (Day 25-29) ]
    Criteria for potential clinically important change in vital signs included: Systolic blood pressure (BP) less than (<) 90 millimeters of mercury (mmHg) or more than or equal to (>=)30 mmHg change from baseline, diastolic BP of <50 mmHg or >=20 mmHg change from baseline, Supine pulse rate of <40 or more than (>)120 beats per minute (bpm).

  6. Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria [ Time Frame: Baseline up to Day 16 ]
    Criteria for potential clinically important changes in ECG (12-lead) were defined as: the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval) >=300 milliseconds (msec) or increase from baseline >=25% when baseline >200 msec or increase from baseline >=50% when baseline less than or equal to (<=) 200 msec; time from the beginning of the electrocardiogram Q wave to the end of the S wave corresponding to ventricular depolarization (QRS) interval >=140 msec or >=50% increase from baseline; the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval corrected using the Fridericia formula (QTcF) of 450 to < 480 msec, 480 to <500 msec and >=500 msec, or an increase of 30 to <60 msec or >=60 msec from baseline.


Secondary Outcome Measures :
  1. 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) ]
  2. 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 [ Time Frame: 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.

  3. Incidence and Severity of Gout Flare Attacks [ Time Frame: Baseline up to Day 42 ]
  4. Duration of Gout Flare Attacks [ Time Frame: Baseline up to Day 42 ]
    Duration of gout flare attacks with participants who developed gout flare attacks.

  5. Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14 [ Time Frame: 0, 1, 2, 4, 8, 12 and 24 hours at Day 1, Day 7, and Day 14 ]
    Data has been calculated by setting concentration values below the lower limit of quantification to zero. The lower limit of quantification was 10.0 nanograms per milliliter (ng/mL).

  6. Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14 [ Time Frame: 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).

  7. Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up [ Time Frame: Baseline, Day 1, Day 7, Day 14, and at follow-up visit (Day 25-29) ]
    Change in plasma levels of xanthine from baseline at time points 0 (prior to dosing except on Day 1), 1, 2, 4, 8, 12 and 24 hours following dosing with PF-06743649 or placebo on days 1, 7 and 14 as well prior to dosing on days 3 and 11 and at follow-up of treatment with PF-06743649 or placebo.

  8. 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) ]
  9. Change From Baseline in Urinary Uric Acid Levels at Day 1, Day 7, and Day 14 [ Time Frame: Baseline, Day 1, Day 7 and Day 14 ]
    Change from baseline in urinary uric acid cumulative amounts.

  10. Change From Baseline in Urinary Xanthine Levels at Day 1, Day 7, and Day 14 [ Time Frame: Baseline, Day 1, Day 7 and Day 14 ]
    Change from baseline in urinary xanthine cumulative amounts.

  11. Change From Baseline in Urinary Hypoxanthine Levels at Day 1, Day 7, and Day 14 [ Time Frame: Baseline, Day 1, Day 7 and Day 14 ]
    Change from baseline in urinary hypoxanthine cumulative amounts at Day 1, Day 7 and Day 14



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02187029


Locations
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United States, Florida
MRA Clinical Research, LLC
Miami, Florida, United States, 33143
Miami Research Associates, Inc.
South Miami, Florida, United States, 33143
United States, Kansas
Vince and Associates Clinical Research Inc.
Overland Park, Kansas, United States, 66211
Vince and Associates Clinical Research, Inc.
Overland Park, Kansas, United States, 66212
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02187029     History of Changes
Other Study ID Numbers: B7911002
First Posted: July 10, 2014    Key Record Dates
Results First Posted: November 11, 2016
Last Update Posted: November 11, 2016
Last Verified: September 2016
Keywords provided by Pfizer:
Hyperuricemia
gout
serum uric acid
Additional relevant MeSH terms:
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Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases