A phase 4 Study to evaluate the safety and efficacy of Lesinurad 200 mg in combination with a Xanthine Oxidase Inhibitor (XOI) compared with XOI alone in subjects with gout.
- Conditions
- Gout and moderate renal impairmentMedDRA version: 20.0Level: PTClassification code 10018627Term: GoutSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2017-001191-30-CZ
- Lead Sponsor
- Ironwood Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
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 <60.0 mL/min.
6.Subject has been taking an XOI as urate-lowering therapy (ULT) treatment of gout for at least 4 weeks prior to Screening at a stable, medically appropriate dose, as determined by the Investigator. The minimum dose of allopurinol is 200 mg daily, and the minimum dose of febuxostat is the lowest approved dose per the local product label.
7.Subject has a serum uric acid level =6.0 mg/dL (357 µmol/L) at Screening Visits 1 and 2.
8.Subject is male or female; females must not be pregnant or breastfeeding and females of childbearing potential must agree to use non-hormonal contraception during the Screening Period and while taking IP.
9.Subject has a body mass index <45 kg/m2.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 510
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method