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] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 determine the efficacy of lesinurad by Month 6 when used in combination with allopurinol compared to allopurinol monotherapy |
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E.2.2 | Secondary objectives of the trial |
•To determine the efficacy of lesinurad by Month 12 when used in combination with allopurinol compared to allopurinol monotherapy •To determine the safety of lesinurad over 6 months and 12 months when used in combination with allopurinol •To investigate by a population analysis approach the influence of intrinsic factors (age, sex, race, body weight, renal function, concomitant medication use) on oral clearance of lesinurad •To determine the effect of lesinurad when used in combination with allopurinol on Health Related Quality of Life an physical function
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subject is able to understand the study procedures, the risks involved and willing to provide written informed consent before the first study related activity. •Subject meets the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout. •Subject has been taking allopurinol as the sole urate-lowering therapy indicated for the treatment of gout for at least 8 weeks prior to the Screening Visit at a stable, medically appropriate dose, as determined by the Investigator, of at least 300 mg per day (at least 200 mg for subjects with moderate renal impairment). •Subject must be able to take gout flare prophylaxis with colchicine or an NSAID (including Cox-2 selective NSAID) ±PPI. •Subject has an sUA level ≥ 6.5 mg/dL (387 μmol/L) at the Screening Visit and ≥ 6.0 mg/dL (357 μmol/L) at the Day -7 Visit.. •Subject has reported at least 2 gout flares in the prior 12 months. •Body mass index < 45 kg/m2. |
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E.4 | Principal exclusion criteria |
•Subject with known hypersensitivity or allergy to allopurinol. •Subject who is taking any other approved urate-lowering medication that is indicated for the treatment of gout other than allopurinol within 8 weeks of the Screening Visit. •Subject who is pregnant or breastfeeding. •Subject who consumes 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). •Subject with a history or suspicion of drug abuse within the past 5 years. •Subject that requires or may require systemic immunosuppressive or immunomodulatory treatment. •Subject with known or suspected human immunodeficiency virus (HIV) infection. •Subject with a positive test for active hepatitis B or hepatitis C infection. •Subject with a history of malignancy within the previous 5 years with the exception of non-melanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia or treated in situ Grade 1 cervical cancer. •Subject within the last 12 months with: unstable angina, New York Heart Association class III or IV heart failure, myocardial infarction, stroke, or deep venous thrombosis; or subjects currently receiving anticoagulants. •Subject with uncontrolled hypertension. •Subject with an estimated creatinine clearance < 30 mL/min. •Subject with active peptic ulcer disease requiring treatment. •Subject with a history of xanthinuria; subject with active liver disease or hepatic dysfunction. •Subject receiving chronic treatment with more than 325 mg of salicylates per day. •Subject taking valpromide, progabide or valproic acid. •Subject who has received an investigational therapy within 8 weeks or 5 half-lives (whichever is longer) prior to the Screening Visit; this does not include locally marketed products used in clinical trials. •Subject with any other medical or psychological condition which might create undue risk to the subject or interfere with the subject’s ability to comply with the protocol requirements, or to complete the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with an sUA level that is < 6.0 mg/dL by Month 6 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Proportion of subjects requiring treatment for a gout flare during Month 12 2. Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient reported outcomes. |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 45 |
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 |
France |
Germany |
New Zealand |
Poland |
South Africa |
Spain |
Switzerland |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |