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Trial record 8 of 13 for:    cardiovascular febuxostat

Intensive Uric Acid Lowering With RDEA3170 and Febuxostat in Chronic Kidney Disease

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2017 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT03118739
First received: April 12, 2017
Last updated: April 13, 2017
Last verified: April 2017
  Purpose
The purpose of this clinical research study is to evaluate signals of potential clinical benefit of the combination of RDEA3170 and Febuxostat in lowering concentrations of circulating uric acid and thus improving kidney or cardiovascular status of patients with hyperuricemia, mild to moderate chronic kidney disease, and Type 2 diabetes (T2DM).

Condition Intervention Phase
Hyperuricemia
Mild to Moderate Chronic Kidney Disease
Type 2 Diabetes
Drug: RDEA3170 9 mg+Febuxostat 80 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, double-blind, double-dummy, placebo-controlled, parallel, independent groups, repeated measures, multi-center study
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Masking Description:
RDEA3170 capsules/matching placebo capsules and febuxostat/matching placebo capsules with randomization code printed on each label
Primary Purpose: Treatment
Official Title: Effects of Intensive Uric Acid Lowering Therapy With RDEA3170 (Verinurad) and Febuxostat in Patients With Chronic Kidney Disease

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Urinary Albumin to Creatinine Ratio (UACR) after 12 weeks [ Time Frame: From baseline to 12 weeks of treatment ]
    To assess the effects of intensive uric acid lowering therapy with RDEA3170 and febuxostat on albuminuria


Secondary Outcome Measures:
  • Estimated glomerular filtration rate (eGFR), Cystatin C, creatinine [ Time Frame: From baseline up to 24 weeks of treatment ]
    To assess the effects of intensive uric acid lowering therapy with RDEA3170 and febuxostat on kidney function.

  • Serum uric acid [ Time Frame: From baseline up to 24 weeks of treatment ]
    To assess the metabolic effects of intensive uric acid lowering therapy with RDEA3170 and febuxostat

  • Left ventricular cardiac strain,function and mass, kidney oxygenation [ Time Frame: From baseline up to 24 weeks of treatment ]
    To assess the structural and functional effects of intensive uric acid lowering therapy with RDEA3170 and febuxostat on the heart and kidney using magnetic resonance imaging

  • High sensitivity C-reactive protein and Troponin I [ Time Frame: From baseline up to 24 weeks of treatment ]
    To assess the effects of intensive uric acid lowering therapy with RDEA3170 and febuxostat on biomarkers and parameters related to inflammation, and cardiac health

  • Blood pressure (systolic and diastolic) [ Time Frame: From baseline up to 24 weeks of treatment ]
    To assess the effects of intensive uric acid lowering therapy with RDEA3170 and febuxostat on cardiovascular parameters

  • RDEA3170 plasma concentration at trough [ Time Frame: From baseline up to 24 weeks of treatment ]
    To assess plasma exposure of RDEA3170 in this patient population


Other Outcome Measures:
  • Rates of adverse events and serious adverse events. Changes in vital signs, physical examinations, and electrocardiograms. Changes in clinical laboratory parameters, including assessment of creatinine, cystatin C, and blood urea nitrogen [ Time Frame: From signing of the infromed consent form until 4 weeks after the last dose ]
    To assess the safety and tolerability of intensive uric acid lowering therapy with RDEA3170 and febuxostat


Estimated Enrollment: 60
Anticipated Study Start Date: May 28, 2017
Estimated Study Completion Date: June 29, 2018
Estimated Primary Completion Date: March 23, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RDEA3170 9 mg+Febuxostat 80 mg
Capsule administered orally, once daily for 24 weeks
Drug: RDEA3170 9 mg+Febuxostat 80 mg
Capsule administered orally, once daily for 24 weeks
Other Name: RDEA3170 (Verinurad), Febuxostat(Uloric)
Placebo Comparator: Placebo
Capsule administered orally, once daily for 24 weeks
Drug: Placebo
Capsule administered orally, once daily for 24 weeks

Detailed Description:

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.

RDEA3170 (verinurad), is a novel Urate Transporter 1 (URAT1) inhibitor in Phase II development. RDEA3170 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 disease 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 mild to moderate CKD 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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, RDEA3170, probenecid, and benzbromarone)
  • Prior history of gout
  • Patients who are pregnant, lactating, or planning to become pregnant
  • Patients unsuitable or unable to undergo MRI assessment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03118739

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Sponsors and Collaborators
AstraZeneca
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03118739     History of Changes
Other Study ID Numbers: D5495C00007
Study First Received: April 12, 2017
Last Updated: April 13, 2017
Individual Participant Data  
Plan to Share IPD: No
Plan Description: IPD will likely not be shared with external collaborators/researchers as this data is planned to be used only for internal decision-making

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Febuxostat
Kidney Diseases
Renal Insufficiency, Chronic
Hyperuricemia
Urologic Diseases
Renal Insufficiency
Pathologic Processes
Uric Acid
Gout Suppressants
Antirheumatic Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 27, 2017