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 | 17.0 |
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 determine the efficacy of lesinurad by Month 6 when used in combination with febuxostat compared to febuxostat 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 febuxostat compared to febuxostat monotherapy
- To determine the safety of lesinurad over 6 months and 12 months when used in combination with febuxostat
- 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 febuxostat on Health Related Quality of Life and 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 meets one of the following criteria:
a.subjects who are not currently taking an approved ULT must have an sUA value of ≥ 8 mg/dL (476 μmol/L).
b.b.subjects entering the study on a medically appropriate dose of
febuxostat or allopurinol must have an sUA value of ≥ 6.0 mg/dL (357μmol/L).
c.subjects entering the study on febuxostat ≥ 80 mg or allopurinol ≥ 600 mg daily must have an sUA value of ≥ 6.0 mg/dL.
Subject must be able to take gout flare prophylaxis with colchicine or NSAID (including Cox-2 selective NSAID) ± PPI.
Subject with at least 1 measurable tophus on the hands/wrists and/or feet/ankles ≥ 5 mm and ≤ 20 mm in the longest diameter.
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E.4 | Principal exclusion criteria |
Subject with known hypersensitivity or allergy to febuxostat.
Subject who is taking any approved urate-lowering medication other than allopurinol or febuxostat that is indicated for the treatment of gout within 8 weeks of the Screening Visit.
Subject who previously received pegloticase.
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 with a history of myositis/myopathy or rhabdomyolysis.
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 (NYHA) 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.
Subjects with a creatine kinase > 2.5 x ULN at any time during the Screening Period.
Subject with active peptic ulcer disease requiring treatment.
Subject with a history of xanthinuria, 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.
Subject with any other medical or psychological condition, which in the opinion of the Investigator and/or Medical Monitor, 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 < 5.0 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 who experience complete resolution of at least 1 target tophus by Month 12
2. Proportion of subjects with a best tophus response on at least 1 target tophus of complete or partial resolution by Month 12
3. Proportion of subjects with an improvement from Baseline in HAQ-DI of at least 0.25 at 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Canada |
France |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |