Intensive Uric Acid Lowering With Verinurad and Febuxostat in Patients With Albuminuria

Type 2 Diabetes Clinical Trial

Official title:

Effects of Intensive Uric Acid Lowering Therapy With RDEA3170 (Verinurad) and Febuxostat in Patients With Albuminuria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03118739
• Other study ID #: D5495C00007
• Status: Completed
• Phase: Phase 2
• Start date: May 18, 2017
• Est. completion date: August 13, 2018

Study information

• Verified date: December 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: August 13, 2018
• Est. primary completion date: August 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Albuminuria
• Hyperuricemia
• Type 2 Diabetes

Intervention

Drug:
• Verinurad 9 mg+Febuxostat 80 mg
Capsule administered orally, once daily for 24 weeks
• Placebo
Capsule administered orally, once daily for 24 weeks

Locations

Country	Name	City	State
United States	Research Site	Canyon Country	California
United States	Research Site	Chula Vista	California
United States	Research Site	Corona	California
United States	Research Site	Escondido	California
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Lakewood	California
United States	Research Site	Lincoln	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	North Hollywood	California
United States	Research Site	Oceanside	California
United States	Research Site	Orange	California
United States	Research Site	Pearland	Texas
United States	Research Site	Sacramento	California
United States	Research Site	Sugar Land	Texas
United States	Research Site	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Flow Mediated Dilatation (Reactive Hyperemia)	LS 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.	From Baseline to 12 Weeks and 24 Weeks of Treatment
Other	Urinalysis	Changes in Urinalysis (CFB = Change from Baseline)	From Baseline to 12 Weeks and 24 Weeks of Treatment
Other	Clinical Chemistry Values	Changes in Clinical Chemistry Values (CFB = Change for Baseline)	From Baseline to 12 Weeks and 24 Weeks of Treatment
Other	Baseline eGFR		Baseline
Other	Baseline UACR		Baseline
Other	Baseline Serum Uric Acid (sUA)		Baseline
Other	Baseline Serum Creatinine		Baseline
Other	Baseline Serum Cystatin-C		Baseline
Other	Baseline Serum High-sensitivity C-reactive Protein		Baseline
Other	Baseline MRI Variables - Kidney Cortex T2 Star		Baseline
Other	Baseline MRI Variables - LV End-diastolic Volume		Baseline
Other	Baseline MRI Variables - LV Ejection Fraction		Baseline
Other	Baseline MRI Variables - LV End-systolic Volume		Baseline
Other	Baseline MRI Variables - Circumferential Strain		Baseline
Other	Baseline MRI Variables - Diastolic Circumferential Strain Rate		Baseline
Other	Baseline MRI Variables - Diastolic Longitudinal Strain Rate		Baseline
Other	Baseline MRI Variables - Diastolic Radial Strain Rate		Baseline
Other	Baseline MRI Variables - Longitudinal Strain		Baseline
Other	Baseline MRI Variables - Radial Strain		Baseline
Other	Baseline MRI Variables - Systolic Circumferential Strain Rate		Baseline
Other	Baseline MRI Variables - Systolic Longitudinal Strain Rate		Baseline
Other	Baseline MRI Variables - Systolic Radial Strain Rate		Baseline
Other	Baseline MRI Variables - LV Mass		Baseline
Other	Baseline MRI Variables - LV Mass/End-diastolic Volume		Baseline
Other	Baseline MRI Variables - LV Stroke Volume		Baseline
Other	Baseline Flow Mediated Dilatation (Reactive Hyperemia)	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.	Baseline
Primary	Urinary Albumin to Creatinine Ratio (UACR)	LS Mean Percentage Change (95% CI) from Baseline in UACR	From Baseline to 12 Weeks of Treatment
Primary	Urinary Albumin to Creatinine Ratio (UACR) Compared to Placebo	LS Mean Percentage Change (90% CI) from Baseline in UACR Compared to Placebo	From Baseline to 24 Weeks of Treatment
Primary	Urinary Albumin to Creatinine Ratio (UACR)	LS Mean Percentage Change (95% CI) from Baseline in UACR	From Baseline to 24 Weeks of Treatment
Secondary	sUA	LS Mean Percentage Change (95% CI) from Baseline in sUA	From Baseline to 12 Weeks and 24 Weeks of Treatment
Secondary	eGFR	LS Mean Percentage Change (95% CI) from Baseline in eGFR	From Baseline to 12 Weeks and 24 Weeks of Treatment
Secondary	Serum Creatinine	LS Mean Percentage Change (95% CI) from Baseline in Serum Creatinine	From Baseline to 12 Weeks and 24 Weeks of Treatment
Secondary	Serum Cystatin C	LS Mean Percentage Change (95% CI) from Baseline in Serum Cystatin C	From Baseline to 12 Weeks and 24 Weeks of Treatment
Secondary	Serum High Sensitivity C-reactive Protein	LS Mean Percentage Change (95% CI) from Baseline in Serum High Sensitivity C-reactive Protein	From Baseline to 12 Weeks and 24 Weeks of Treatment
Secondary	Clinical Assessments	Change from Baseline in Diastolic and Systolic Blood Pressure	From Baseline to 12 Weeks and 24 Weeks of Treatment
Secondary	MRI Variables - LV Mass/End-diastolic Volume	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)	From Baseline to 24 Weeks of Treatment
Secondary	MRI Variables - Kidney Cortex T2 Star - BOLD MRI	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)	From Baseline to 24 Weeks of Treatment
Secondary	MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)	From Baseline to 24 Weeks of Treatment
Secondary	MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain	Change from baseline in MRI Variables at Week 24 (CFB = Change from Baseline)	From Baseline to 24 Weeks of Treatment
Secondary	MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)	From Baseline to 24 Weeks of Treatment
Secondary	MRI Variables - LV Mass	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)	From Baseline to 24 Weeks of Treatment

External Links

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