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

NCT02187029 | Terminated Phase 1 Results

• 1 other identifier: B7911002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

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.

Conditions

Gout

Keywords

Hyperuricemia; gout; serum uric acid

Outcome Measures

Primary Outcomes (6)

• Baseline of Serum Uric Acid

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

  Baseline (pre-dose Day 1)

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

  Day 14 Hour 24

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

  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.

  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).

  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).

  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.

  Baseline up to Day 16

Secondary Outcomes (11)

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

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

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

  24 hours post dose on Day 7 and Day 14

• Incidence and Severity of Gout Flare Attacks

  Baseline up to Day 42

• Duration of Gout Flare Attacks

  Baseline up to Day 42

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

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

Study Arms (4)

PF-06743649 dose level 1 (Cohort 1)

EXPERIMENTAL

Drug: PF-06743649

Placebo for PF-06743649 (Cohort 1)

PLACEBO COMPARATOR

Other: Placebo

PF-06743649 dose level 2 (Cohort 2)

EXPERIMENTAL

Drug: PF-06743649

Placebo for PF-06743649 (Cohort 2)

PLACEBO COMPARATOR

Other: Placebo

Interventions

PF-06743649 DRUG

Daily dosing (dose level 1) tablet for 14 days

PF-06743649 dose level 1 (Cohort 1)

Placebo OTHER

Daily dosing (tablet) for 14 days

Placebo for PF-06743649 (Cohort 1)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (4)

MRA Clinical Research, LLC

Miami, Florida, 33143, United States

Location

Miami Research Associates, Inc.

South Miami, Florida, 33143, United States

Location

Vince and Associates Clinical Research Inc.

Overland Park, Kansas, 66211, United States

Location

Vince and Associates Clinical Research, Inc.

Overland Park, Kansas, 66212, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Gout; Hyperuricemia

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2014
• First Posted: July 10, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: November 11, 2016
• Results First Posted: November 11, 2016

Record last verified: 2016-09

Locations

US (4)