E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018627 |
E.1.2 | Term | Gout |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of allopurinol at medically appropriate doses (at least 200 mg daily). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the serum urate (sUA) lowering capabilities of allopurinol in gout patients with hyperuricemia.
• To evaluate the incidence of gout flares requiring treatment in gout patients taking allopurinol.
• To evaluate health-related quality of life (QOL) and disability outcomes in gout patients taking allopurinol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient is 18 to 85 years of age.
- Patient meets the diagnosis of gout according to the American Rheumatism Association (ARA) Criteria for the Classification of Acute Arthritis of Primary Gout.
- Patients not on a ULT must have an sUA level ≥ 8.0 mg/dL at screening.
- Patients on concomitant ULT must have an sUA level ≥ 6.5 mg/dL at screening.
- Patient must have had at least 2 gout flares in the past year. |
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E.4 | Principal exclusion criteria |
- Patient who consumes more than 14 drinks of alcohol per week (e.g., 1 drink = 5 oz[150 mL] of wine, 12 oz [360 mL] of beer, or 1.5 oz [45 mL] of hard liquor).
- Patient with a history or suspicion of drug abuse.
- Patient with a history of autoimmune disease requiring systemic treatment.
- Patient with a known or suspected human immunodeficiency virus (HIV), hepatitis C antibody (HCV), or hepatitis B antibody (HBsAg) infection.
- Patient with a 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).
- Patient with myocardial infarction, unstable angina, New York Heart Association (NYHA) class III or IV heart failure, or stroke within the last 12 months.
- Patient with uncontrolled hypertension (systolic pressure above 160 mm Hg or diastolic pressure above 95 mm Hg).
- Patient with an estimated creatinine clearance < 30 mL/min by Cockcroft-Gault formula.
- Patient with a kidney or other organ transplant.
- Patient with active peptic ulcer disease requiring treatment.
- Patient with a history of xanthinuria, active liver disease, or hepatic dysfunction.
- Patient who is unable to take gout flare prophylaxis of either colchicine or NSAID due to
contraindication (e.g., toxicity, renal function, use of contraindicated medications).
- Patient with known hypersensitivity or allergy to allopurinol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of treatment-emergent AEs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every month for 6 months. |
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E.5.2 | Secondary end point(s) |
• Proportion of patients with an sUA level that is < 6.0 mg/dL at the last study visit.
• Proportion of patients whose sUA levels are < 6.0 mg/dL, < 5.0 mg/dL and
< 4.0 mg/dL at each monthly visit.
• Absolute and percent reduction from baseline in sUA levels at monthly intervals.
• Change from baseline in the physical and mental component scales of the SF-36.
• Proportion of patients with at least a 0.25 point improvement in the HAQ-DI.
• Change from baseline in the SDS.
• Change from baseline in the PGA.
• Incidence of gout flares requiring treatment.
• Absolute changes and shifts from baseline in laboratory parameters.
• Absolute changes and shifts from baseline in vital signs. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
Germany |
New Zealand |
South Africa |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |