ClinicalTrials.gov processed this data on March 28, 2024Link to the current ClinicalTrials.gov record.https://clinicaltrials.gov/ct2/show/NCT03118739D5495C00007NCT03118739Intensive Uric Acid Lowering With Verinurad and Febuxostat in Patients With AlbuminuriaEffects of Intensive Uric Acid Lowering Therapy With RDEA3170 (Verinurad) and Febuxostat in Patients With AlbuminuriaAstraZenecaIndustryNoYesNo
The purpose of this clinical research study is to evaluate signals of potential clinical
benefit of the combination of Verinurad and Febuxostat in lowering concentrations of
circulating uric acid and thus improving kidney or cardiovascular status of patients with
hyperuricemia, albuminuria, and Type 2 diabetes (T2DM).
Evidence shows independent associations between elevated serum uric acid (sUA) and the risk
of hypertension, myocardial infarction (MI), chronic kidney disease (CKD), T2DM, heart
failure (HF), and metabolic syndrome, including obesity. Gout is associated with an increased
risk of all-cause death, as well as cardiovascular death. The causal relationship between
elevated sUA, gout, and these disease outcomes remains to be proven.
Verinurad (RDEA3170), is a novel Urate Transporter 1 (URAT1) inhibitor in Phase II
development. Verinurad combined with the xanthine oxidase (XO) inhibitor febuxostat has been
shown to lower sUA in patients with recurrent gout in Phase II studies by >80%. The extensive
lowering of sUA delivered by the combination presents a unique opportunity to explore whether
intensive urate lowering therapy can improve kidney and/or cardiac health.
This study will assess if intensive serum urate lowering therapy, more potent than ever
explored before in the chronic out-patient setting, can improve chronic kidney or cardiac
function in the study population.
In order to maximize the scientific value of the study and minimize the risk for systemic
biases a parallel group, double blind, randomized design will be utilized.
The study will recruit patients with hyperuricemia and presenting with albuminuria.
Hyperuricemic patients are expected to benefit more from urate lowering, and albuminuria at
baseline is required, as the primary objective of the study will be to assess changes in
albuminuria.
Patients are also required to be diagnosed with T2DM. Patients with T2DM frequently exhibit
changes in cardiac function detectable using magnetic resonance imaging (MRI) that represents
an early, pre-symptomatic state of HF. By limiting recruitment to patients with T2DM and by
performing MRI at baseline and 6 months of therapy, the study will deliver insights into
whether or not intensive urate lowering therapy can positively affect not only chronic kidney
disease, but also cardiac disease.
CompletedMay 18, 2017August 13, 2018August 13, 2018Phase 2InterventionalNoRandomizedParallel AssignmentRandomized, double-blind, double-dummy, placebo-controlled, parallel, independent groups, repeated measures, multi-center studyTreatmentQuadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Verinurad capsules/matching placebo capsules and febuxostat/matching placebo capsules with randomization code printed on each labelUrinary Albumin to Creatinine Ratio (UACR)From Baseline to 12 Weeks of TreatmentLS Mean Percentage Change (95% CI) from Baseline in UACRUrinary Albumin to Creatinine Ratio (UACR) Compared to PlaceboFrom Baseline to 24 Weeks of TreatmentLS Mean Percentage Change (90% CI) from Baseline in UACR Compared to PlaceboUrinary Albumin to Creatinine Ratio (UACR)From Baseline to 24 Weeks of TreatmentLS Mean Percentage Change (95% CI) from Baseline in UACRsUAFrom Baseline to 12 Weeks and 24 Weeks of TreatmentLS Mean Percentage Change (95% CI) from Baseline in sUAeGFRFrom Baseline to 12 Weeks and 24 Weeks of TreatmentLS Mean Percentage Change (95% CI) from Baseline in eGFRSerum CreatinineFrom Baseline to 12 Weeks and 24 Weeks of TreatmentLS Mean Percentage Change (95% CI) from Baseline in Serum CreatinineSerum Cystatin CFrom Baseline to 12 Weeks and 24 Weeks of TreatmentLS Mean Percentage Change (95% CI) from Baseline in Serum Cystatin CSerum High Sensitivity C-reactive ProteinFrom Baseline to 12 Weeks and 24 Weeks of TreatmentLS Mean Percentage Change (95% CI) from Baseline in Serum High Sensitivity C-reactive ProteinClinical AssessmentsFrom Baseline to 12 Weeks and 24 Weeks of TreatmentChange from Baseline in Diastolic and Systolic Blood PressureMRI Variables - LV Mass/End-diastolic VolumeFrom Baseline to 24 Weeks of TreatmentChange from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)MRI Variables - Kidney Cortex T2 Star - BOLD MRIFrom Baseline to 24 Weeks of TreatmentChange from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke VolumeFrom Baseline to 24 Weeks of TreatmentChange from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial StrainFrom Baseline to 24 Weeks of TreatmentChange from baseline in MRI Variables at Week 24 (CFB = Change from Baseline)MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain RateFrom Baseline to 24 Weeks of TreatmentChange from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)MRI Variables - LV MassFrom Baseline to 24 Weeks of TreatmentChange from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)Flow Mediated Dilatation (Reactive Hyperemia)From Baseline to 12 Weeks and 24 Weeks of TreatmentLS Mean Change (95% CI) from Baseline in Flow Mediated Dilatation. The flow mediated dilatation metric is obtained using a device from Cordex, and a proprietary algorithm.
This metric represents the volume difference between a baseline arterial compliance curve and hyperemia arterial compliance curve in the positive transmural pressure region. This metric has a direct relationship to a subject's cardiovascular condition. Output range is 0-150. A higher score is indicative of a better flow mediated dilatation.UrinalysisFrom Baseline to 12 Weeks and 24 Weeks of TreatmentChanges in Urinalysis (CFB = Change from Baseline)Clinical Chemistry ValuesFrom Baseline to 12 Weeks and 24 Weeks of TreatmentChanges in Clinical Chemistry Values (CFB = Change for Baseline)Baseline eGFRBaselineBaseline UACRBaselineBaseline Serum Uric Acid (sUA)BaselineBaseline Serum CreatinineBaselineBaseline Serum Cystatin-CBaselineBaseline Serum High-sensitivity C-reactive ProteinBaselineBaseline MRI Variables - Kidney Cortex T2 StarBaselineBaseline MRI Variables - LV End-diastolic VolumeBaselineBaseline MRI Variables - LV Ejection FractionBaselineBaseline MRI Variables - LV End-systolic VolumeBaselineBaseline MRI Variables - Circumferential StrainBaselineBaseline MRI Variables - Diastolic Circumferential Strain RateBaselineBaseline MRI Variables - Diastolic Longitudinal Strain RateBaselineBaseline MRI Variables - Diastolic Radial Strain RateBaselineBaseline MRI Variables - Longitudinal StrainBaselineBaseline MRI Variables - Radial StrainBaselineBaseline MRI Variables - Systolic Circumferential Strain RateBaselineBaseline MRI Variables - Systolic Longitudinal Strain RateBaselineBaseline MRI Variables - Systolic Radial Strain RateBaselineBaseline MRI Variables - LV MassBaselineBaseline MRI Variables - LV Mass/End-diastolic VolumeBaselineBaseline MRI Variables - LV Stroke VolumeBaselineBaseline Flow Mediated Dilatation (Reactive Hyperemia)BaselineBaseline in Flow Mediated Dilatation. The flow mediated dilatation metric is obtained using a device from Cordex, and a proprietary algorithm.
This metric represents the volume difference between a baseline arterial compliance curve and hyperemia arterial compliance curve in the positive transmural pressure region. This metric has a direct relationship to a subject's cardiovascular condition. Output range is 0-150. A higher score is indicative of a better flow mediated dilatation.260HyperuricemiaAlbuminuriaType 2 DiabetesVerinurad 9 mg+Febuxostat 80 mgExperimentalCapsule administered orally, once daily for 24 weeksPlaceboPlacebo ComparatorCapsule administered orally, once daily for 24 weeksDrugVerinurad 9 mg+Febuxostat 80 mgCapsule administered orally, once daily for 24 weeksVerinurad 9 mg+Febuxostat 80 mgVerinurad (RDEA3170), Febuxostat(Uloric)DrugPlaceboCapsule administered orally, once daily for 24 weeksPlacebo
Inclusion Criteria:
- Serum Uric Acid ≥6.0 mg/dL
- eGFR ≥30 mL/min/1.73 m2
- UACR between 30 mg/g and 3500 mg/g inclusive
- Diagnosed with T2DM
Exclusion Criteria:
- Treated with any drug for hyperuricemia in the 6 months preceding randomization.Drugs
for hyperuricemia include all XO inhibitors (allopurinol, febuxostat and topiroxostat)
and URAT1 inhibitors (lesinurad, verinurad, probenecid, and benzbromarone)
- Prior history of gout, unless prophylaxis therapy isn't required
- Patients who are pregnant, lactating, or planning to become pregnant
- Patients unsuitable or unable to undergo MRI assessment
All18 Years99 YearsNoResearch SiteCanyon CountryCalifornia91351United StatesResearch SiteChula VistaCalifornia91911United StatesResearch SiteCoronaCalifornia92882United StatesResearch SiteEscondidoCalifornia92025United StatesResearch SiteLakewoodCalifornia90805United StatesResearch SiteLincolnCalifornia95648United StatesResearch SiteLos AngelesCalifornia90017United StatesResearch SiteLos AngelesCalifornia90022United StatesResearch SiteLos AngelesCalifornia90036United StatesResearch SiteNorth HollywoodCalifornia91606United StatesResearch SiteOceansideCalifornia92056-4510United StatesResearch SiteOrangeCalifornia92868United StatesResearch SiteSacramentoCalifornia95821United StatesResearch SiteHoustonTexas77058United StatesResearch SiteHoustonTexas77070United StatesResearch SitePearlandTexas77584United StatesResearch SiteSugar LandTexas77478United StatesResearch SiteWebsterTexas77598United StatesUnited Stateshttps://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D5495C00007&attachmentIdentifier=7ba9d99a-a3d8-4550-9897-42c1821775ff&fileName=d5495c00007_csp_Redacted.pdf&versionIdentifier=Redacted Protocolhttps://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D5495C00007&attachmentIdentifier=fe54e85c-c086-4dca-89de-900472089931&fileName=d5495c00007_sap_Redacted.pdf&versionIdentifier=redacted SAPDecember 2019April 12, 2017April 13, 2017April 18, 2017July 15, 2019December 18, 2019January 10, 2020December 18, 2019December 18, 2019January 10, 2020SponsorAlbuminuriaHyperuricemiaFebuxostatVerinuradNoIndividual participant data (IPD) will likely not be shared with external collaborators/researchers as this data is planned to be used only for internal decision-makingStudy Protocol and Statistical Analysis PlanYesNoYesSeptember 13, 2018https://ClinicalTrials.gov/ProvidedDocs/39/NCT03118739/Prot_SAP_000.pdf