Gout
Conditions
Brief summary
This is a study of allopurinol in gout patients with hyperuricemia that will evaluate the safety and serum urate (sUA) lowering capability of allopurinol as a urate lowering therapy (ULT) for up to six months. Allopurinol will be dosed according to the local product label, at the discretion of the Investigator, to achieve an optimal, medically appropriate dose for each patient.
Interventions
DRUGAllopurinol
Commercially available allopurinol 100 mg and 300 mg oral tablets will be prescribed by the Investigator according to the approved product label.
Sponsors
Ardea Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Meets the diagnosis of gout according to the American Rheumatism Association (ARA) Criteria for the Classification of Acute Arthritis of Primary Gout. * Not on a urate lowering therapy (ULT) must have an sUA level ≥ 8.0 mg/dL at screening. * If on concomitant ULT must have an sUA level ≥ 6.5 mg/dL at screening. * Must have had at least 2 gout flares in the past year.
Exclusion criteria
* Consumption of more than 14 drinks of alcohol per week (eg, 1 drink = 5 oz \[150 mL\] of wine, 12 oz \[360 mL\] of beer, or 1.5 oz \[45 mL\] of hard liquor). * History or suspicion of drug abuse. * History of autoimmune disease requiring systemic treatment. * Known or suspected human immunodeficiency virus (HIV), hepatitis C antibody (HCV), or hepatitis B antibody (HBsAg) infection. * History of malignancy within the previous 5 years (with the exception of nonmelanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia or treated in situ Grade 1 cervical cancer). * Myocardial infarction, unstable angina, New York Heart Association (NYHA) class III or IV heart failure, or stroke within the last 12 months. * Uncontrolled hypertension (systolic pressure above 160 mm Hg or diastolic pressure above 95 mm Hg). * Estimated creatinine clearance \< 30 mL/min by Cockcroft-Gault formula. * Kidney or other organ transplant. * Active peptic ulcer disease requiring treatment. * History of xanthinuria, active liver disease, or hepatic dysfunction. * If unable to take gout flare prophylaxis of either colchicine or nonsteroidal anti-inflammatory drugs (NSAIDs) due to contraindication (e.g. toxicity, renal function, use of contraindicated medications). * Known hypersensitivity or allergy to allopurinol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Allopurinol | Every month for 6 months. | Proportion of subjects who experienced at least one Treatment Emergent Adverse Event (TEAE) during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Serum Urate (sUA) Less Than 6.0 mg/dL | Month 6 | Proportion of subjects with serum urate (sUA) less than 6.0 mg/dL at Month 6 using Last Observation Carried Forward (LOCF) for subjects with missing values at Month 6. |
| Incidence of Gout Flares | Every month for 6 months. | Proportion of subjects who experienced at least one gout flare requiring treatment during the study. |
| Mean Change From Baseline to Month 6 in SF-36 PCS+MCS | Month 6 | The SF-36 is a short-form health survey with 36 questions that yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical (PCS) and mental health (MCS) summary. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. The higher the score the less disability. The component scores (PCS and MCS) are norm-based to a standard population with a mean of 50 and a standard deviation of 10. |
Countries
Australia, Belgium, Canada, Germany, New Zealand, South Africa, United States
Participant flow
Pre-assignment details
1,735 subjects enrolled in the study; however, only 1,732 were treated. Therefore, 1,732 subjects started the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Allopurinol Treatment.
Allopurinol: Commercially available allopurinol 100 mg and 300 mg oral tablets will be prescribed by the Investigator according to the approved product label. | 1,732 |
| Total | 1,732 |
Baseline characteristics
| Characteristic | Allopurinol |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 249 Participants |
| Age, Categorical Between 18 and 65 years | 1483 Participants |
| Age, Continuous | 51.4 years STANDARD_DEVIATION 11.93 |
| Region of Enrollment Australia | 104 participants |
| Region of Enrollment Belgium | 11 participants |
| Region of Enrollment Canada | 74 participants |
| Region of Enrollment Germany | 14 participants |
| Region of Enrollment New Zealand | 84 participants |
| Region of Enrollment South Africa | 242 participants |
| Region of Enrollment United States | 1203 participants |
| Sex: Female, Male Female | 118 Participants |
| Sex: Female, Male Male | 1614 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 654 / 1,732 |
| serious Total, serious adverse events | 52 / 1,732 |
Outcome results
Primary
Safety of Allopurinol
Proportion of subjects who experienced at least one Treatment Emergent Adverse Event (TEAE) during the study.
Time frame: Every month for 6 months.
Population: All subjects who received at least one dose of allopurinol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allopurinol | Safety of Allopurinol | 55.1 percentage of subjects |
Secondary
Incidence of Gout Flares
Proportion of subjects who experienced at least one gout flare requiring treatment during the study.
Time frame: Every month for 6 months.
Population: Subjects who received at least one dose of allopurinol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allopurinol | Incidence of Gout Flares | 33.4 percentage of subjects |
Secondary
Mean Change From Baseline to Month 6 in SF-36 PCS+MCS
The SF-36 is a short-form health survey with 36 questions that yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical (PCS) and mental health (MCS) summary. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. The higher the score the less disability. The component scores (PCS and MCS) are norm-based to a standard population with a mean of 50 and a standard deviation of 10.
Time frame: Month 6
Population: Subjects who recieved at least one dose of allopurinol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Allopurinol | Mean Change From Baseline to Month 6 in SF-36 PCS+MCS | SF-36 Physical Component Summary | 3.88 units on a scale | Standard Deviation 8.458 |
| Allopurinol | Mean Change From Baseline to Month 6 in SF-36 PCS+MCS | SF-36 Mental Health Component Summary | 0.71 units on a scale | Standard Deviation 9.076 |
Secondary
Proportion of Subjects With Serum Urate (sUA) Less Than 6.0 mg/dL
Proportion of subjects with serum urate (sUA) less than 6.0 mg/dL at Month 6 using Last Observation Carried Forward (LOCF) for subjects with missing values at Month 6.
Time frame: Month 6
Population: All subjects who received at least one dose of allopurinol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allopurinol | Proportion of Subjects With Serum Urate (sUA) Less Than 6.0 mg/dL | 43.4 percentage of subjects |