Chronic Kidney Disease (CKD), Gout
Conditions
Brief summary
This study evaluates the safety and efficacy of lesinurad administered with an XOI versus a placebo plus an XOI in gout participants who have moderate renal impairment and who are not at target level of serum urate (sUA).
Detailed description
This postmarketing study is a randomized, double-blind, placebo-controlled study to evaluate safety (with particular focus on renal and cardiovascular events) and efficacy of lesinurad 200 mg once daily (QD) in combination with an XOI for up to 24 months compared with XOI monotherapy, in participants with gout and moderate renal impairment who have not reached target sUA levels (\<6.0 mg/dL) on an XOI alone.
Interventions
DRUGLesinurad
200 mg oral tablet
DRUGXOI
All participants must be on a stable, medically appropriate dose of XOI as their sole urate-lowering therapy (ULT) indicated for the treatment of gout for at least 4 weeks prior to Screening and throughout the Screening Period. This stable dose of XOI will be maintained throughout the study period.
DRUGPlacebo
matching placebo oral tablet
DRUGcolchicine
Gout flare prophylaxis: commercially available colchicine is provided through the Month 6 study visit. Actual colchicine dose (0.5 or 0.6 mg qd) and frequency were adjusted based on the local label, subject medical history, and clinical judgement.
DRUGcorticosteroids
Gout flare prophylaxis: Participants unable to take colchicine are permitted to take a short course of low-dose oral corticosteroids up to the Month 3 study visit
Sponsors
Medpace, Inc.
Ironwood Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
active vs placebo visually identical tablets
Intervention model description
Randomized, Double-Blind, Multicenter, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
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 ULT indicated for the 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 nonhormonal contraception during the Screening Period and while taking investigation product (IP). 9. Subject has a body mass index \< 45 kg/m\^2.
Exclusion criteria
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 ranolazine, 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 Cytochrome P450 3A4 (CYP3A4) 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 computerized tomography (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 |
|---|---|
| Percentage of Participants Who Achieve Serum Urate (sUA) < 6.0 mg/dL at Month 6 | Month 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Estimated Creatinine Clearance (eCrCl) at Month 24 | Baseline, 24 months | The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight. |
| Percent Change From Baseline in eCrCl at Month 24 | Baseline, 24 months | The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight. |
| Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Baseline, Months 1, 3, 6, 9, 12, 15, 18 | The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight. |
| Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Baseline, Months 1, 3, 6, 9, 12, 15, 18 | The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight. |
| Percentage of Participants With Serum Creatinine (sCr) Elevations (≥1.5 × Baseline) Over the Study Period | up to 18 months | — |
| Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Baseline, Months 1, 3, 6, 9, 12, 15, 18 | — |
| Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Baseline, Months 1, 3, 6, 9, 12, 15, 18 | — |
| Percentage of Participants Meeting Criteria (eg, Based on sCr or eCrCl Criteria) for Treatment Discontinuations Over the Study Period | up to 18 months | Kidney function was monitored throughout the study by measuring sCr and calculating eCrCl by Cockcroft-Gault formula using ideal body weight. Treatment discontinuations were required if a participant experienced an absolute sCr ≥4.0 mg/dL or an eCrCl \<20 mL/min (based on central laboratory results). |
| Percentage of Participants Renal-Related and Kidney Stone Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose of study drug through each participant's study duration, up to approximately 18 months. | Renal-related and kidney stone events were based on Medical Dictionary for Regulatory Activities (MedDRA) Renal and Urinary Disorders system organ classification. AEs that started on or after the first dose of study drug in this study, or those AEs with onset prior to the first dose of study drug but worsened after the first dose of study drug, were considered treatment emergent. |
| Percentage of Participants With Contributing Factors to Renal SAEs as Adjudicated by the Renal Event Adjudication Committee (REAC) | From first dose of study drug through each participant's study duration, up to approximately 18 months. | — |
| Percentage of Participants With Cardiac Event Adjudication Committee (CEAC)-Adjudicated Major Adverse Cardiovascular Events (MACEs) | From first dose of study drug through each participant's study duration, up to approximately 18 months. | MACEs are defined as Cardiovascular Death, Nonfatal Myocardial Infarction, and Nonfatal Stroke. |
| Incidence of CEAC-Adjudicated MACEs or Hospitalization for Unstable Angina (MACE+) | From first dose of study drug through each participant's study duration, up to approximately 18 months. | MACEs are defined as Cardiovascular Death, Nonfatal Myocardial Infarction, and Nonfatal Stroke. |
| Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Baseline, Months 1, 3, 6, 9, 12, 15, 18 | — |
Countries
Czechia, Hungary, Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo + XOI placebo oral tablet QD plus a stable, medically appropriate dose of an XOI | 118 |
| Lesinurad + XOI lesinurad 200 mg oral tablet QD plus a stable, medically appropriate dose of an XOI | 124 |
| Total | 242 |
Baseline characteristics
| Characteristic | Lesinurad + XOI | Total | Placebo + XOI |
|---|---|---|---|
| Age, Continuous | 66.4 years STANDARD_DEVIATION 10.1 | 66.8 years STANDARD_DEVIATION 9.12 | 67.3 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 46 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 104 Participants | 196 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 38 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 95 Participants | 194 Participants | 99 Participants |
| Sex: Female, Male Female | 28 Participants | 50 Participants | 22 Participants |
| Sex: Female, Male Male | 96 Participants | 192 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 118 | 0 / 124 |
| other Total, other adverse events | 9 / 118 | 18 / 124 |
| serious Total, serious adverse events | 7 / 118 | 13 / 124 |
Outcome results
Primary
Percentage of Participants Who Achieve Serum Urate (sUA) < 6.0 mg/dL at Month 6
Time frame: Month 6
Population: Modified Intent-to-Treat (mITT) Population: all randomized participants who received at least 1 dose of study drug. Participants with a value at Month 6.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + XOI | Percentage of Participants Who Achieve Serum Urate (sUA) < 6.0 mg/dL at Month 6 | 33.8 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Who Achieve Serum Urate (sUA) < 6.0 mg/dL at Month 6 | 58.8 percentage of participants |
Secondary
Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment
The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight.
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Population: Safety Population: all randomized participants who received at least 1 dose of lesinurad or placebo. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 1 | 0.13 mL/min | Standard Deviation 9.67 |
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 3 | -0.69 mL/min | Standard Deviation 7.41 |
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 6 | -1.84 mL/min | Standard Deviation 7.58 |
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 9 | -0.78 mL/min | Standard Deviation 6.85 |
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 12 | -2.14 mL/min | Standard Deviation 7.03 |
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 15 | 0.36 mL/min | Standard Deviation 6.07 |
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 18 | -19.0 mL/min | — |
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Last On-Treatment Visit | -1.03 mL/min | Standard Deviation 6.97 |
| Placebo + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Last Off-Treatment Visit | 2.33 mL/min | Standard Deviation 5.61 |
| Lesinurad + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 1 | -1.29 mL/min | Standard Deviation 6.45 |
| Lesinurad + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 12 | -4.30 mL/min | Standard Deviation 6.34 |
| Lesinurad + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 3 | -1.53 mL/min | Standard Deviation 8.65 |
| Lesinurad + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Last Off-Treatment Visit | -2.45 mL/min | Standard Deviation 5.41 |
| Lesinurad + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 6 | -1.80 mL/min | Standard Deviation 7.02 |
| Lesinurad + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 15 | -6.00 mL/min | Standard Deviation 8.49 |
| Lesinurad + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 9 | -2.10 mL/min | Standard Deviation 7.97 |
| Lesinurad + XOI | Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Last On-Treatment Visit | -1.91 mL/min | Standard Deviation 8.19 |
Secondary
Change From Baseline in Estimated Creatinine Clearance (eCrCl) at Month 24
The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight.
Time frame: Baseline, 24 months
Population: Due to early study termination, no participant reached Month 24. Therefore these data are not available.
Secondary
Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Population: Safety Population: all randomized participants who received at least 1 dose of lesinurad or placebo. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 6 | -54.6 µmol/L | Standard Deviation 103.1 |
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 1 | -57.0 µmol/L | Standard Deviation 96.2 |
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 3 | -59.8 µmol/L | Standard Deviation 98.6 |
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 9 | -70.6 µmol/L | Standard Deviation 128.4 |
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 12 | -78.7 µmol/L | Standard Deviation 122.4 |
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 15 | -92.6 µmol/L | Standard Deviation 91.4 |
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 18 | 0.00 µmol/L | — |
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Last On-Treatment Visit | -57.0 µmol/L | Standard Deviation 104.7 |
| Placebo + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Last Off-Treatment Visit | -70.7 µmol/L | Standard Deviation 105.4 |
| Lesinurad + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 12 | -69.6 µmol/L | Standard Deviation 110.4 |
| Lesinurad + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 1 | -120.3 µmol/L | Standard Deviation 105.3 |
| Lesinurad + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Last Off-Treatment Visit | -156.6 µmol/L | Standard Deviation 149.2 |
| Lesinurad + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 3 | -106.8 µmol/L | Standard Deviation 116.2 |
| Lesinurad + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 6 | -125.8 µmol/L | Standard Deviation 140 |
| Lesinurad + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 15 | -116.6 µmol/L | Standard Deviation 76.3 |
| Lesinurad + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 9 | -95.9 µmol/L | Standard Deviation 106.5 |
| Lesinurad + XOI | Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Last On-Treatment Visit | -125.5 µmol/L | Standard Deviation 121.4 |
Secondary
Incidence of CEAC-Adjudicated MACEs or Hospitalization for Unstable Angina (MACE+)
MACEs are defined as Cardiovascular Death, Nonfatal Myocardial Infarction, and Nonfatal Stroke.
Time frame: From first dose of study drug through each participant's study duration, up to approximately 18 months.
Population: This was not analyzed; no events were adjudicated since the study was terminated early.
Secondary
Percentage of Participants Meeting Criteria (eg, Based on sCr or eCrCl Criteria) for Treatment Discontinuations Over the Study Period
Kidney function was monitored throughout the study by measuring sCr and calculating eCrCl by Cockcroft-Gault formula using ideal body weight. Treatment discontinuations were required if a participant experienced an absolute sCr ≥4.0 mg/dL or an eCrCl \<20 mL/min (based on central laboratory results).
Time frame: up to 18 months
Population: Safety Population: all randomized participants who received at least 1 dose of lesinurad or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + XOI | Percentage of Participants Meeting Criteria (eg, Based on sCr or eCrCl Criteria) for Treatment Discontinuations Over the Study Period | 0.0 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Meeting Criteria (eg, Based on sCr or eCrCl Criteria) for Treatment Discontinuations Over the Study Period | 0.0 percentage of participants |
Secondary
Percentage of Participants Renal-Related and Kidney Stone Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Renal-related and kidney stone events were based on Medical Dictionary for Regulatory Activities (MedDRA) Renal and Urinary Disorders system organ classification. AEs that started on or after the first dose of study drug in this study, or those AEs with onset prior to the first dose of study drug but worsened after the first dose of study drug, were considered treatment emergent.
Time frame: From first dose of study drug through each participant's study duration, up to approximately 18 months.
Population: All Randomized Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + XOI | Percentage of Participants Renal-Related and Kidney Stone Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-Emergent SAEs | 0.0 percentage of participants |
| Placebo + XOI | Percentage of Participants Renal-Related and Kidney Stone Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-Emergent AEs | 4.2 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Renal-Related and Kidney Stone Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-Emergent SAEs | 0.8 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Renal-Related and Kidney Stone Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-Emergent AEs | 5.6 percentage of participants |
Secondary
Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Population: mITT Population: all randomized participants who received at least 1 dose of study drug. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Baseline | 10.3 percentage of participants |
| Placebo + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 1 | 35.1 percentage of participants |
| Placebo + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 3 | 36.4 percentage of participants |
| Placebo + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 6 | 33.8 percentage of participants |
| Placebo + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 9 | 34.0 percentage of participants |
| Placebo + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 12 | 42.9 percentage of participants |
| Placebo + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 15 | 45.5 percentage of participants |
| Placebo + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 18 | 0.0 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Baseline | 10.6 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 12 | 56.5 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 1 | 58.8 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 9 | 42.9 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 3 | 52.5 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 15 | 62.5 percentage of participants |
| Lesinurad + XOI | Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time | Month 6 | 58.8 percentage of participants |
Secondary
Percentage of Participants With Cardiac Event Adjudication Committee (CEAC)-Adjudicated Major Adverse Cardiovascular Events (MACEs)
MACEs are defined as Cardiovascular Death, Nonfatal Myocardial Infarction, and Nonfatal Stroke.
Time frame: From first dose of study drug through each participant's study duration, up to approximately 18 months.
Population: This was not analyzed; no events were adjudicated since the study was terminated early.
Secondary
Percentage of Participants With Contributing Factors to Renal SAEs as Adjudicated by the Renal Event Adjudication Committee (REAC)
Time frame: From first dose of study drug through each participant's study duration, up to approximately 18 months.
Population: This was not analyzed; no events were adjudicated since the study was terminated early.
Secondary
Percentage of Participants With Serum Creatinine (sCr) Elevations (≥1.5 × Baseline) Over the Study Period
Time frame: up to 18 months
Population: Safety Population: all randomized participants who received at least 1 dose of lesinurad or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + XOI | Percentage of Participants With Serum Creatinine (sCr) Elevations (≥1.5 × Baseline) Over the Study Period | 5.2 percentage of participants |
| Lesinurad + XOI | Percentage of Participants With Serum Creatinine (sCr) Elevations (≥1.5 × Baseline) Over the Study Period | 7.3 percentage of participants |
Secondary
Percent Change From Baseline in eCrCl at Month 24
The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight.
Time frame: Baseline, 24 months
Population: Due to early study termination, no participant reached Month 24. Therefore these data are not available.
Secondary
Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment
The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight.
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Population: Safety Population: all randomized participants who received at least 1 dose of lesinurad or placebo. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 9 | -0.26 percent change | Standard Deviation 18.67 |
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 1 | 1.16 percent change | Standard Deviation 19.9 |
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 3 | -0.18 percent change | Standard Deviation 17.7 |
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 6 | -2.49 percent change | Standard Deviation 17.96 |
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 12 | -3.38 percent change | Standard Deviation 15.71 |
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 15 | 3.67 percent change | Standard Deviation 18.6 |
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 18 | -31.7 percent change | — |
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Last On-Treatment Visit | -1.13 percent change | Standard Deviation 16.86 |
| Placebo + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Last Off-Treatment Visit | 4.14 percent change | Standard Deviation 13.67 |
| Lesinurad + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 12 | -8.1 percent change | Standard Deviation 12.9 |
| Lesinurad + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 1 | -2.07 percent change | Standard Deviation 15.3 |
| Lesinurad + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Last Off-Treatment Visit | -5.35 percent change | Standard Deviation 13.52 |
| Lesinurad + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 3 | -2.14 percent change | Standard Deviation 20.12 |
| Lesinurad + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 15 | -11.0 percent change | Standard Deviation 16.5 |
| Lesinurad + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 6 | -3.01 percent change | Standard Deviation 15.32 |
| Lesinurad + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Month 9 | -3.42 percent change | Standard Deviation 17.05 |
| Lesinurad + XOI | Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment | Change at Last On-Treatment Visit | -3.04 percent change | Standard Deviation 18.21 |
Secondary
Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Population: Safety Population: all randomized participants who received at least 1 dose of lesinurad or placebo. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 1 | -11.3 percent change | Standard Deviation 18.8 |
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 3 | -11.4 percent change | Standard Deviation 18.8 |
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 6 | -10.0 percent change | Standard Deviation 21.7 |
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 9 | -12.6 percent change | Standard Deviation 27.3 |
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 12 | -15.2 percent change | Standard Deviation 22.8 |
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 15 | -18.9 percent change | Standard Deviation 17.5 |
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 18 | 0.00 percent change | — |
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Last On-Treatment Visit | -10.6 percent change | Standard Deviation 22.1 |
| Placebo + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Last Off-Treatment Visit | -16.1 percent change | Standard Deviation 25.8 |
| Lesinurad + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 1 | -24.0 percent change | Standard Deviation 19.3 |
| Lesinurad + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 12 | -14.7 percent change | Standard Deviation 26.7 |
| Lesinurad + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 3 | -21.2 percent change | Standard Deviation 21.7 |
| Lesinurad + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Last Off-Treatment Visit | -27.3 percent change | Standard Deviation 22.6 |
| Lesinurad + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 6 | -23.9 percent change | Standard Deviation 24.4 |
| Lesinurad + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 15 | -26.1 percent change | Standard Deviation 16.3 |
| Lesinurad + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Month 9 | -18.6 percent change | Standard Deviation 20.2 |
| Lesinurad + XOI | Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment | Change at Last On-Treatment Visit | -24.8 percent change | Standard Deviation 22.8 |