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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03118739
• Collaborator: (none)
• Enrollment: 60
• Locations: 18
• Arms: 2
• Actual Duration (Months): 14.9
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Hyperuricemia; Albuminuria; Type 2 Diabetes	Drug: Verinurad 9 mg+Febuxostat 80 mg; Drug: Placebo	Phase 2

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.

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, double-dummy, placebo-controlled, parallel, independent groups, repeated measures, multi-center studyRandomized, double-blind, double-dummy, placebo-controlled, parallel, independent groups, repeated measures, multi-center study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Verinurad 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 Albuminuria
• Actual Study Start Date: May 18, 2017
• Actual Primary Completion Date: Aug 13, 2018
• Actual Study Completion Date: Aug 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Verinurad 9 mg+Febuxostat 80 mg Capsule administered orally, once daily for 24 weeks	Drug: Verinurad 9 mg+Febuxostat 80 mg; Capsule administered orally, once daily for 24 weeks; Other Names: Verinurad (RDEA3170), Febuxostat(Uloric)
Placebo Comparator: Placebo Capsule administered orally, once daily for 24 weeks	Drug: Placebo; Capsule administered orally, once daily for 24 weeks

Outcome Measures

Primary Outcome Measures

1. Urinary Albumin to Creatinine Ratio (UACR) [From Baseline to 12 Weeks of Treatment]

   LS Mean Percentage Change (95% CI) from Baseline in UACR

2. Urinary Albumin to Creatinine Ratio (UACR) Compared to Placebo [From Baseline to 24 Weeks of Treatment]

   LS Mean Percentage Change (90% CI) from Baseline in UACR Compared to Placebo

3. Urinary Albumin to Creatinine Ratio (UACR) [From Baseline to 24 Weeks of Treatment]

   LS Mean Percentage Change (95% CI) from Baseline in UACR

Secondary Outcome Measures

1. sUA [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   LS Mean Percentage Change (95% CI) from Baseline in sUA

2. eGFR [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   LS Mean Percentage Change (95% CI) from Baseline in eGFR

3. Serum Creatinine [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   LS Mean Percentage Change (95% CI) from Baseline in Serum Creatinine

4. Serum Cystatin C [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   LS Mean Percentage Change (95% CI) from Baseline in Serum Cystatin C

5. Serum High Sensitivity C-reactive Protein [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   LS Mean Percentage Change (95% CI) from Baseline in Serum High Sensitivity C-reactive Protein

6. Clinical Assessments [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   Change from Baseline in Diastolic and Systolic Blood Pressure

7. MRI Variables - LV Mass/End-diastolic Volume [From Baseline to 24 Weeks of Treatment]

   Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)

8. MRI Variables - Kidney Cortex T2 Star - BOLD MRI [From Baseline to 24 Weeks of Treatment]

   Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)

9. MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume [From Baseline to 24 Weeks of Treatment]

   Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)

10. MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain [From Baseline to 24 Weeks of Treatment]

    Change from baseline in MRI Variables at Week 24 (CFB = Change from Baseline)

11. MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate [From Baseline to 24 Weeks of Treatment]

    Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)

12. MRI Variables - LV Mass [From Baseline to 24 Weeks of Treatment]

    Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)

Other Outcome Measures

1. Flow Mediated Dilatation (Reactive Hyperemia) [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   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.

2. Urinalysis [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   Changes in Urinalysis (CFB = Change from Baseline)

3. Clinical Chemistry Values [From Baseline to 12 Weeks and 24 Weeks of Treatment]

   Changes in Clinical Chemistry Values (CFB = Change for Baseline)

4. Baseline eGFR [Baseline]

5. Baseline UACR [Baseline]

6. Baseline Serum Uric Acid (sUA) [Baseline]

7. Baseline Serum Creatinine [Baseline]

8. Baseline Serum Cystatin-C [Baseline]

9. Baseline Serum High-sensitivity C-reactive Protein [Baseline]

10. Baseline MRI Variables - Kidney Cortex T2 Star [Baseline]

11. Baseline MRI Variables - LV End-diastolic Volume [Baseline]

12. Baseline MRI Variables - LV Ejection Fraction [Baseline]

13. Baseline MRI Variables - LV End-systolic Volume [Baseline]

14. Baseline MRI Variables - Circumferential Strain [Baseline]

15. Baseline MRI Variables - Diastolic Circumferential Strain Rate [Baseline]

16. Baseline MRI Variables - Diastolic Longitudinal Strain Rate [Baseline]

17. Baseline MRI Variables - Diastolic Radial Strain Rate [Baseline]

18. Baseline MRI Variables - Longitudinal Strain [Baseline]

19. Baseline MRI Variables - Radial Strain [Baseline]

20. Baseline MRI Variables - Systolic Circumferential Strain Rate [Baseline]

21. Baseline MRI Variables - Systolic Longitudinal Strain Rate [Baseline]

22. Baseline MRI Variables - Systolic Radial Strain Rate [Baseline]

23. Baseline MRI Variables - LV Mass [Baseline]

24. Baseline MRI Variables - LV Mass/End-diastolic Volume [Baseline]

25. Baseline MRI Variables - LV Stroke Volume [Baseline]

26. Baseline Flow Mediated Dilatation (Reactive Hyperemia) [Baseline]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Canyon Country	California	United States	91351
2	Research Site	Chula Vista	California	United States	91911
3	Research Site	Corona	California	United States	92882
4	Research Site	Escondido	California	United States	92025
5	Research Site	Lakewood	California	United States	90805
6	Research Site	Lincoln	California	United States	95648
7	Research Site	Los Angeles	California	United States	90017
8	Research Site	Los Angeles	California	United States	90022
9	Research Site	Los Angeles	California	United States	90036
10	Research Site	North Hollywood	California	United States	91606
11	Research Site	Oceanside	California	United States	92056-4510
12	Research Site	Orange	California	United States	92868
13	Research Site	Sacramento	California	United States	95821
14	Research Site	Houston	Texas	United States	77058
15	Research Site	Houston	Texas	United States	77070
16	Research Site	Pearland	Texas	United States	77584
17	Research Site	Sugar Land	Texas	United States	77478
18	Research Site	Webster	Texas	United States	77598

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 13, 2018

More Information

Additional Information:

• Redacted Protocol
• redacted SAP

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03118739
• Other Study ID Numbers: D5495C00007
• First Posted: Apr 18, 2017
• Last Update Posted: Jan 10, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Albuminuria; Hyperuricemia; Febuxostat; Verinurad

Study Results

Participant Flow

Recruitment Details	This study was conducted at 19 clinical research centers in the United States of America. First subject enrolled (First subject first visit/first consent signed date): 18 May 2017. Last subject last visit: 13 August 2018.
Pre-assignment Detail	Patients were screened at Visit 1. Within 1 week, eligible patients collected 3 morning void samples on consecutive days for proteinuria measurements. Patients with acceptable results were scheduled for Visit 2. Prior to randomization and before or on the day of Visit 2, patients underwent MRI. V2 occurred no later than 6 weeks after V1.

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Period Title: Overall Study
STARTED	32	28
Completed 12 Weeks of Treatment	26	25
Completed 24 Weeks of Treatment	24	25
COMPLETED	25	24
NOT COMPLETED	7	4

Baseline Characteristics

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo	Total
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks	Total of all reporting groups
Overall Participants	32	28	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 50%	17 60.7%	33 55%
>=65 years	16 50%	11 39.3%	27 45%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.0 (9.51)	60.9 (12.15)	61.5 (10.74)
Sex: Female, Male (Count of Participants)
Female	10 31.3%	8 28.6%	18 30%
Male	22 68.8%	20 71.4%	42 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 34.4%	7 25%	18 30%
Not Hispanic or Latino	21 65.6%	21 75%	42 70%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 9.4%	4 14.3%	7 11.7%
Native Hawaiian or Other Pacific Islander	1 3.1%	0 0%	1 1.7%
Black or African American	6 18.8%	5 17.9%	11 18.3%
White	22 68.8%	15 53.6%	37 61.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	4 14.3%	4 6.7%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	93.72 (20.243)	96.76 (19.561)	95.14 (19.818)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	170.57 (10.662)	170.75 (9.117)	170.65 (9.888)
Body Mass Index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	32.00 (5.082)	32.95 (4.699)	32.44 (4.889)
estimated glomerular filtration rate (eGFR) (Count of Participants)
eGFR<30	2 6.3%	1 3.6%	3 5%
eGFR >=30 to <60	16 50%	9 32.1%	25 41.7%
eGFR >=60 to <90	9 28.1%	12 42.9%	21 35%
eGFR >=90	5 15.6%	6 21.4%	11 18.3%

Outcome Measures

1. Primary Outcome

Title	Urinary Albumin to Creatinine Ratio (UACR)
Description	LS Mean Percentage Change (95% CI) from Baseline in UACR
Time Frame	From Baseline to 12 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Least Squares Mean (95% Confidence Interval) [Precent change]	-48.65	-15.31

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Verinurad 9 mg+Febuxostat 80 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean % Change from Baseline
	Estimated Value	-39.37
	Confidence Interval	(2-Sided) 90%; -61.785 to -3.814
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	sUA
Description	LS Mean Percentage Change (95% CI) from Baseline in sUA
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
12 weeks	-56.81	6.86
24 weeks	-61.93	4.73

3. Secondary Outcome

Title	eGFR
Description	LS Mean Percentage Change (95% CI) from Baseline in eGFR
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
12 weeks	1.25	-4.40
24 weeks	-1.73	0.55

4. Secondary Outcome

Title	Serum Creatinine
Description	LS Mean Percentage Change (95% CI) from Baseline in Serum Creatinine
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
12 weeks	-0.60	3.44
24 weeks	1.93	0.02

5. Secondary Outcome

Title	Serum Cystatin C
Description	LS Mean Percentage Change (95% CI) from Baseline in Serum Cystatin C
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
12 weeks	3.252	0.114
24 weeks	5.412	3.951

6. Secondary Outcome

Title	Serum High Sensitivity C-reactive Protein
Description	LS Mean Percentage Change (95% CI) from Baseline in Serum High Sensitivity C-reactive Protein
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
12 weeks	35.863	11.665
24 weeks	-8.002	9.793

7. Secondary Outcome

Title	Clinical Assessments
Description	Change from Baseline in Diastolic and Systolic Blood Pressure
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Diastolic BP, mmHg Baseline	74.7 (9.83)	77.8 (11.91)
Diastolic BP, mmHg 12 weeks (Change from baseline)	1.6 (11.02)	-0.2 (9.51)
Diastolic BP, mmHg 24 weeks (Change from baseline)	2.0 (8.53)	1.7 (12.05)
Systolic BP, mmHg Baseline	136.4 (15.13)	138.5 (16.34)
Systolic BP, mmHg 12 weeks (Change from baseline)	-0.8 (19.00)	-3.2 (15.48)
Systolic BP, mmHg 24 weeks (Change from baseline)	0.4 (9.75)	-0.6 (17.78)

8. Secondary Outcome

Title	MRI Variables - LV Mass/End-diastolic Volume
Description	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame	From Baseline to 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [g/mL]	0.049 (0.1445)	0.053 (0.1202)

9. Other Pre-specified Outcome

Title	Flow Mediated Dilatation (Reactive Hyperemia)
Description	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.
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
12 weeks Change from Baseline	0.8	-5.9
24 weeks Change from Baseline	0.5	-5.5

10. Other Pre-specified Outcome

Title	Urinalysis
Description	Changes in Urinalysis (CFB = Change from Baseline)
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Baseline Protein, mg/dL	72.01 (99.767)	65.74 (78.686)
Protein, mg/dL 12 weeks (CFB)	-11.40 (65.896)	-4.07 (71.047)
Protein, mg/dL 24 weeks (CFB)	-16.73 (101.052)	11.40 (76.645)
Baseline Urine Albumin, mg/dL	38.0907 (55.62178)	35.8905 (47.17446)
Urine Albumin, mg/dL 12 weeks (CFB)	-9.4766 (35.73442)	-0.3019 (45.81688)
Urine Albumin, mg/dL 24 weeks (CFB)	-6.9482 (50.66844)	11.6049 (53.13042)
Baseline Urine Creatinine, mg/dL	96.52 (51.570)	86.25 (46.189)
Urine Creatinine, mg/dL 12 weeks (CFB)	5.06 (53.378)	12.95 (34.987)
Urine Creatinine, mg/dL 24 weeks (CFB)	7.58 (55.930)	8.53 (36.430)
Baseline Urine Urate, mg/dL	28.354 (12.0591)	23.960 (10.6862)
Urine Urate, mg/dL 12 weeks (CFB)	-13.394 (13.2757)	3.560 (12.3875)
Urine Urate, mg/dL 24 weeks (CFB)	-10.732 (16.4720)	2.294 (9.3407)

11. Other Pre-specified Outcome

Title	Clinical Chemistry Values
Description	Changes in Clinical Chemistry Values (CFB = Change for Baseline)
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Baseline Aldosterone, pmol/L	134.58 (126.126)	95.11 (72.640)
Aldosterone, pmol/L 12 weeks (CFB)	1.12 (118.622)	14.72 (72.485)
Aldosterone, pmol/L 24 weeks (CFB)	9.14 (102.932)	38.14 (90.007)
Baseline NT-proBNP, pmol/L	23.230 (22.6864)	15.866 (28.2147)
NT-proBNP, pmol/L 12 weeks (CFB)	4.621 (31.1027)	1.556 (10.0140)
NT-proBNP, pmol/L 24 weeks (CFB)	6.267 (19.0367)	15.866 (46.4392)

12. Primary Outcome

Title	Urinary Albumin to Creatinine Ratio (UACR) Compared to Placebo
Description	LS Mean Percentage Change (90% CI) from Baseline in UACR Compared to Placebo
Time Frame	From Baseline to 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Least Squares Mean (90% Confidence Interval) [Precent change]	-49.26	NA

13. Secondary Outcome

Title	MRI Variables - Kidney Cortex T2 Star - BOLD MRI
Description	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame	From Baseline to 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [ms]	-1.46 (6.511)	-1.67 (6.440)

14. Secondary Outcome

Title	MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume
Description	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame	From Baseline to 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
LV End-diastolic Volume (mL) (CFB)	-5.39 (27.458)	-4.93 (20.665)
LV End-systolic Volume (mL) (CFB)	1.33 (14.106)	-2.48 (10.703)
LV Stroke Volume (mL) (CFB)	-6.73 (15.923)	-2.44 (12.458)

15. Secondary Outcome

Title	MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain
Description	Change from baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame	From Baseline to 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
LV Ejection Fraction (%) (CFB)	-2.08 (3.761)	0.59 (3.374)
Circumferential Strain (%) (CFB)	-0.25 (2.321)	-0.07 (2.192)
Longitudinal Strain (%) (CFB)	0.29 (1.949)	0.53 (1.729)
Radial Strain (%) (CFB)	-2.29 (7.136)	1.44 (8.109)

16. Secondary Outcome

Title	MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate
Description	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame	From Baseline to 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Diastolic Circumferential Strain Rate (s^-1) (CFB)	-0.0496 (0.13769)	-0.0384 (0.13791)
Diastolic Longitudinal Strain Rate (s^-1) (CFB)	-0.0043 (0.10629)	-0.0300 (0.16940)
Diastolic Radial Strain Rate (s^-1) (CFB)	0.2348 (0.43676)	0.0201 (0.72927)
Systolic Circumferential Strain Rate (s^-1) (CFB)	0.0115 (0.11314)	-0.0743 (0.11616)
Systolic Longitudinal Strain Rate (s^-1) (CFB)	0.0285 (0.08436)	-0.0021 (0.08052)
Systolic Radial Strain Rate (s^-1) (CFB)	-0.1917 (0.31833)	0.2516 (0.38049)

17. Secondary Outcome

Title	MRI Variables - LV Mass
Description	Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame	From Baseline to 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [g]	1.80 (7.532)	2.63 (9.994)

18. Other Pre-specified Outcome

Title	Urinalysis
Description	Changes in Urinalysis (CFB = Change from Baseline)
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Baseline Protein/Creatinine, mg/g	945.56 (1457.714)	828.52 (987.671)
Protein/Creatinine, mg/g 12 weeks (CFB)	-185.33 (366.340)	-155.44 (584.772)
Protein/Creatinine, mg/g 24 weeks (CFB)	-98.60 (397.778)	177.11 (1387.627)

19. Other Pre-specified Outcome

Title	Clinical Chemistry Values
Description	Changes in Clinical Chemistry Values (CFB = Change for Baseline)
Time Frame	From Baseline to 12 Weeks and 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Baseline Hemoglobin A1C/Hemoglobin, %	8.14 (1.913)	8.28 (2.025)
Hemoglobin A1C/Hemoglobin, % 12 weeks (CFB)	0.20 (1.399)	0.13 (1.159)
Hemoglobin A1C/Hemoglobin, % 24 weeks (CFB)	-0.14 (0.884)	0.22 (1.863)

20. Other Pre-specified Outcome

Title	Baseline eGFR
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [mL/min/1.73m2]	59.2 (25.25)	68.1 (23.15)

21. Other Pre-specified Outcome

Title	Baseline UACR
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [mg/g]	459.05 (824.731)	411.55 (547.816)

22. Other Pre-specified Outcome

Title	Baseline Serum Uric Acid (sUA)
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [mg/dL]	7.51 (1.558)	7.02 (0.813)

23. Other Pre-specified Outcome

Title	Baseline Serum Creatinine
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [mg/dL]	1.40 (0.595)	1.19 (0.362)

24. Other Pre-specified Outcome

Title	Baseline Serum Cystatin-C
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [mg/L]	1.579 (0.5274)	1.313 (0.3532)

25. Other Pre-specified Outcome

Title	Baseline Serum High-sensitivity C-reactive Protein
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Mean (Standard Deviation) [mg/dL]	0.410 (0.3670)	0.358 (0.2506)

26. Other Pre-specified Outcome

Title	Baseline MRI Variables - Kidney Cortex T2 Star
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	27
Mean (Standard Deviation) [ms]	81.13 (12.995)	82.31 (11.625)

27. Other Pre-specified Outcome

Title	Baseline MRI Variables - LV End-diastolic Volume
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [mL]	161.47 (37.766)	161.50 (32.639)

28. Other Pre-specified Outcome

Title	Baseline MRI Variables - LV Ejection Fraction
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [% (percentage of LV volume)]	59.77 (7.869)	60.19 (6.134)

29. Other Pre-specified Outcome

Title	Baseline MRI Variables - LV End-systolic Volume
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [mL]	66.43 (26.089)	64.63 (17.977)

30. Other Pre-specified Outcome

Title	Baseline MRI Variables - Circumferential Strain
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [% (change in percentage in LV dimension)]	-14.10 (3.925)	-15.37 (2.901)

31. Other Pre-specified Outcome

Title	Baseline MRI Variables - Diastolic Circumferential Strain Rate
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [s^-1]	0.6371 (0.24946)	0.7588 (0.21276)

32. Other Pre-specified Outcome

Title	Baseline MRI Variables - Diastolic Longitudinal Strain Rate
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [s^-1]	0.4833 (0.21090)	0.5258 (0.16476)

33. Other Pre-specified Outcome

Title	Baseline MRI Variables - Diastolic Radial Strain Rate
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [s^-1]	-2.3143 (1.08926)	-2.7591 (1.05712)

34. Other Pre-specified Outcome

Title	Baseline MRI Variables - Longitudinal Strain
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [% (change in percentage in LV dimension)]	-12.07 (3.779)	-12.21 (3.102)

35. Other Pre-specified Outcome

Title	Baseline MRI Variables - Radial Strain
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [% (change in percentage in LV dimension)]	43.47 (15.943)	46.45 (12.743)

36. Other Pre-specified Outcome

Title	Baseline MRI Variables - Systolic Circumferential Strain Rate
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [s^-1]	-0.7673 (0.19408)	-0.7797 (0.12776)

37. Other Pre-specified Outcome

Title	Baseline MRI Variables - Systolic Longitudinal Strain Rate
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [s^-1]	-0.6278 (0.16784)	-0.6552 (0.12734)

38. Other Pre-specified Outcome

Title	Baseline MRI Variables - Systolic Radial Strain Rate
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [s^-1]	2.1059 (0.66890)	2.1220 (0.58484)

39. Other Pre-specified Outcome

Title	Baseline MRI Variables - LV Mass
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [g]	110.27 (26.229)	110.82 (28.487)

40. Other Pre-specified Outcome

Title	Baseline MRI Variables - LV Mass/End-diastolic Volume
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [g/mL]	0.696 (0.1437)	0.687 (0.1163)

41. Other Pre-specified Outcome

Title	Baseline MRI Variables - LV Stroke Volume
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with MRI (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	26
Mean (Standard Deviation) [mL]	95.05 (19.327)	96.86 (21.286)

42. Other Pre-specified Outcome

Title	Baseline Flow Mediated Dilatation (Reactive Hyperemia)
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Total number differs from Study totals due to subject non compliance with exam (exam not completed)

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	29	26
Mean (Standard Deviation) [Units on a scale]	60.4 (28.76)	60.6 (30.90)

43. Primary Outcome

Title	Urinary Albumin to Creatinine Ratio (UACR)
Description	LS Mean Percentage Change (95% CI) from Baseline in UACR
Time Frame	From Baseline to 24 Weeks of Treatment

Outcome Measure Data

Analysis Population Description

Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations

Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg	Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks	Capsule administered orally, once daily for 24 weeks
Measure Participants	32	28
Least Squares Mean (95% Confidence Interval) [Precent change]	-38.40	21.40

Adverse Events

Time Frame	Adverse Events were collected from time of signature of informed consent (Screening Visit) throughout the treatment period and including the follow-up period (Day 190).
Adverse Event Reporting Description	AEs were spontaneously reported by the patient or reported in response to an open question from the study site staff.
Arm/Group Title	Verinurad 9 mg+Febuxostat 80 mg		Placebo
Arm/Group Description	Capsule administered orally, once daily for 24 weeks		Capsule administered orally, once daily for 24 weeks
All Cause Mortality
	Verinurad 9 mg+Febuxostat 80 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/28 (0%)
Serious Adverse Events
	Verinurad 9 mg+Febuxostat 80 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/32 (15.6%)		3/28 (10.7%)
Cardiac disorders
Acute Myocardial Infarction	0/32 (0%)	0	1/28 (3.6%)	1
Cardiac Failure Congestive	0/32 (0%)	0	1/28 (3.6%)	1
Gastrointestinal disorders
Abdominal Distension	1/32 (3.1%)	1	0/28 (0%)	0
Infections and infestations
Bronchitis	1/32 (3.1%)	1	0/28 (0%)	0
Injury, poisoning and procedural complications
Rib Fracture	1/32 (3.1%)	1	0/28 (0%)	0
Road Traffic Accident	1/32 (3.1%)	1	0/28 (0%)	0
Investigations
Troponin I Increased	0/32 (0%)	0	1/28 (3.6%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/32 (3.1%)	1	0/28 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	1/32 (3.1%)	1	0/28 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/32 (3.1%)	2	0/28 (0%)	0
Surgical and medical procedures
Wound Drainage	0/32 (0%)	0	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Verinurad 9 mg+Febuxostat 80 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/32 (28.1%)		2/28 (7.1%)
Gastrointestinal disorders
Diarrhoea	4/32 (12.5%)	4	1/28 (3.6%)	1
Infections and infestations
Nasopharyngitis	2/32 (6.3%)	2	1/28 (3.6%)	1
Nervous system disorders
Dizziness	3/32 (9.4%)	3	0/28 (0%)	0

Limitations/Caveats

The treatment code was broken for 3 patients.The effect of verinurad/febuxostat on sUA was underestimated as drug was administered after collection of blood samples.3 patients treated with verinurad/febuxostat had no detectable drug in PK samples.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.