Gout and moderate renal impairment MedDRA version: 20.0 Level: PT Classification code 10018627 Term: Gout System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Ironwood Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each subject must meet the following criteria to be enrolled in this study. 1.Subject is able to understand the study procedures, the risks involved, and willing to provide written informed consent before the first study related activity. 2.Subject is willing to adhere to the protocol schedule. 3.Subject is =18 years and =85 years of age. 4.Subject has a diagnosis of gout. 5.Subject has moderate renal impairment with estimated creatinine clearance (eCrCl calculated by the Cockcroft-Gault formula using ideal body weight) 25.0 to =65.0 mL/min at Screening Visits 1 and 2 and an average eCrCl for both screening visits of 30.0 to =65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: Subjects who meet the following criterion will be excluded from the study: 1.Subject had unstable angina, New York Heart Association class III or IV heart failure, myocardial infarction, or stroke within the last 6 months prior to randomization; or had a deep venous thrombosis within the previous 3 months prior to randomization. 2.Subject has uncontrolled hypertension (defined as systolic pressure above 160 or diastolic pressure above 95 mm Hg at either Screening Visits 1 or 2). 3.Subject has severe hepatic impairment (defined as Child-Pugh Class C) or is known human immunodeficiency virus (HIV) positive. 4.Subject is a solid organ transplant recipient. 5.Subject has a urine protein of 3+ or higher by dipstick by the central laboratory at Screening Visit 2. 6.Subject has a history of glomerulonephritis. 7.Subject is taking valpromide, progabide, valproic acid, or other known inhibitors of epoxide hydrolase, or subject is taking ranolazone, cyclosporine, azathioprine or mercaptopurine. 8.Subject is receiving chronic treatment with more than 325 mg of salicylates per day. 9.Subject is unable to initiate gout flare prophylaxis with colchicine or low-dose oral corticosteroids at Baseline. 10.Subject is taking any other drug approved for use as a urate-lowering medication other than allopurinol or febuxostat (eg, pegloticase, probenecid, benzbromarone) within 4 weeks prior to Screening or during Screening. 11.For subjects who will be taking colchicine for gout flare prophylaxis: Subject is taking, or anticipated to take during the first 6 months on study, moderate or strong CYP3A inhibitors (ie, verapamil or diltiazem, clarithromycin, and fluconazole) or grapefruit or grapefruit juice. 12.Subject previously participated in a clinical study involving lesinurad (RDEA594) or verinurad (RDEA3170) and received active treatment or placebo, or has taken commercially-available lesinurad. 13.Subject has a gout flare during the Screening Period. 14.Subject is pregnant or breastfeeding. 15.Subject 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). 16.Subject has a history of malignancy and has been on active treatment within the previous 5 years prior to randomization with the exception of non-melanoma skin cancer, treated in situ Grade 1 cervical cancer, or treated ductal carcinoma in situ of the breast. 17.Subject has been hospitalized (other than for elective surgery) or received intravenous contrast (eg, for CT scan or any angiography) within 1 month prior to Screening or during Screening. 18.Subject has participated in a clinical trial within 8 weeks prior to Screening. 19.Subject has any other medical or psychological condition, which in the opinion of the Investigator 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. 20.The maximum number of subjects in the eCrCl stratification subgroup has been reached.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Safety Endpoints -Absolute and percent change from Baseline in eCrCl to Month 24. -Absolute and percent change from Baseline in eCrCl over the study period, including the last value on and off treatment. -Incidence of sCr elevations (=1.5 × Baseline) over the study period. -Incidence of subjects meeting criteria (eg, based on sCr or eCrCl criteria) for treatment discontinuations over the study period. -Incidence of renal-related and kidney stone TEAEs and SAEs. -Prevalence of contributing factors to renal SAEs as adjudicated by the REAC. -Incidence of CEAC-adjudicated Major Adverse Cardiovascular Event (MACE): CV death, nonfatal myocardial infarction, and nonfatal stroke. -Incidence of CEAC-adjudicated MACE or hospitalization for unstable angina (MACE+). ;Main Objective: To evaluate the safety over 24 months of lesinurad 200 mg once daily (qd) when used in combination with a xanthine oxidase inhibitor (XOI), compared with XOI alone, in subjects with gout and moderate renal impairment (estimated creatinine clearance 30 to <60 mL/min) who have not reached target serum uric acid (sUA) levels on an XOI alone.;Secondary Objective: Efficacy Objective: To evaluate the efficacy over 24 months of lesinurad 200 mg qd in combination with an XOI, compared with XOI alone, in subjects with gout and moderate renal impairment who have not reached target sUA levels on an XOI alone.;Timepoint(s) of evaluation of this end point: Month 24 and over the study period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Exploratory end points: -Percent change from Baseline in the sum of the areas of all target tophi at scheduled visits, among subjects with =1 target tophus at Baseline. -Proportion of subjects who experienced complete resolution of at least 1 target tophus at any time during study, among subjects with =1 target tophus at Baseline. -Functional impairment assessed employing the Sheehan Disability Scale (SDS; individual domains as well as total functional impairment) at last on-study visit. -Work productivity as assessed employing the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP; absenteeism, presenteeism, work productivity loss, and activity impairment) at last on-study visit. -Health status as assessed employing the EuroQol Five Dimensions Questionnaire 3 level (EQ-5D-3L; both descriptive system and visual analogue scale) at last on-study visit. -Proportion of subjects with gout flares at each 3-month interval during the study period. Efficacy Endpoints -Key efficacy endpoint: Proportion of subjects who achieve sUA <6.0 mg/dL at Month 6. -Absolute and percent change from Baseline in sUA at each visit. -Proportions of subjects who achieve sUA <6.0 mg/dL at each visit. ;Timepoint(s) of evaluation of this end point: Month 6 and last on -study visit | — |
Countries
Czech Republic, Hungary, Poland, United States
Contacts
Public ContactRegulatory Affairs
Ironwood Pharmaceuticals, Inc.
Outcome results
None listed