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

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ClinicalTrials.gov Identifier: NCT03118739
Recruitment Status : Completed
First Posted : April 18, 2017
Results First Posted : January 10, 2020
Last Update Posted : January 10, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Hyperuricemia
Albuminuria
Type 2 Diabetes
Interventions Drug: Verinurad 9 mg+Febuxostat 80 mg
Drug: Placebo
Enrollment 60
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 Details 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
Hide 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
Reason Not Completed
Physician Decision             0             1
Withdrawal by Subject             5             3
Lost to Follow-up             2             0
Arm/Group Title Verinurad 9 mg+Febuxostat 80 mg Placebo Total
Hide 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 Number of Baseline Participants 32 28 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 28 participants 60 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
16
  50.0%
17
  60.7%
33
  55.0%
>=65 years
16
  50.0%
11
  39.3%
27
  45.0%
[1]
Measure Description: Age at Randomization
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 28 participants 60 participants
62.0  (9.51) 60.9  (12.15) 61.5  (10.74)
[1]
Measure Description: Age at Screening
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 28 participants 60 participants
Female
10
  31.3%
8
  28.6%
18
  30.0%
Male
22
  68.8%
20
  71.4%
42
  70.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 28 participants 60 participants
Hispanic or Latino
11
  34.4%
7
  25.0%
18
  30.0%
Not Hispanic or Latino
21
  65.6%
21
  75.0%
42
  70.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 28 participants 60 participants
American Indian or Alaska Native
0
   0.0%
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
   0.0%
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%
0
   0.0%
Unknown or Not Reported
0
   0.0%
4
  14.3%
4
   6.7%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 32 participants 28 participants 60 participants
93.72  (20.243) 96.76  (19.561) 95.14  (19.818)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 32 participants 28 participants 60 participants
170.57  (10.662) 170.75  (9.117) 170.65  (9.888)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 32 participants 28 participants 60 participants
32.00  (5.082) 32.95  (4.699) 32.44  (4.889)
estimated glomerular filtration rate (eGFR)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 28 participants 60 participants
eGFR<30
2
   6.3%
1
   3.6%
3
   5.0%
eGFR >=30 to <60
16
  50.0%
9
  32.1%
25
  41.7%
eGFR >=60 to <90
9
  28.1%
12
  42.9%
21
  35.0%
eGFR >=90
5
  15.6%
6
  21.4%
11
  18.3%
1.Primary Outcome
Title Urinary Albumin to Creatinine Ratio (UACR)
Hide Description LS Mean Percentage Change (95% CI) from Baseline in UACR
Time Frame From Baseline to 12 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Precent change
-48.65
(-64.807 to -25.089)
-15.31
(-43.244 to 26.370)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Verinurad 9 mg+Febuxostat 80 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean % Change from Baseline
Estimated Value -39.37
Confidence Interval (2-Sided) 90%
-61.785 to -3.814
Estimation Comments [Not Specified]
2.Primary Outcome
Title Urinary Albumin to Creatinine Ratio (UACR) Compared to Placebo
Hide Description LS Mean Percentage Change (90% CI) from Baseline in UACR Compared to Placebo
Time Frame From Baseline to 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (90% Confidence Interval)
Unit of Measure: Precent change
-49.26
(-68.206 to -19.009)
NA [1] 
(NA to NA)
[1]
The primary endpoint is a comparison
3.Primary Outcome
Title Urinary Albumin to Creatinine Ratio (UACR)
Hide Description LS Mean Percentage Change (95% CI) from Baseline in UACR
Time Frame From Baseline to 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Precent change
-38.40
(-58.051 to -9.535)
21.40
(-18.948 to 81.829)
4.Secondary Outcome
Title sUA
Hide Description LS Mean Percentage Change (95% CI) from Baseline in sUA
Time Frame From Baseline to 12 Weeks and 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
12 weeks Number Analyzed 30 participants 26 participants
-56.81
(-63.879 to -48.350)
6.86
(-11.800 to 29.471)
24 weeks Number Analyzed 27 participants 24 participants
-61.93
(-68.274 to -54.319)
4.73
(-13.795 to 27.239)
5.Secondary Outcome
Title eGFR
Hide Description LS Mean Percentage Change (95% CI) from Baseline in eGFR
Time Frame From Baseline to 12 Weeks and 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
12 weeks Number Analyzed 30 participants 26 participants
1.25
(-6.520 to 9.674)
-4.40
(-12.258 to 4.154)
24 weeks Number Analyzed 27 participants 24 participants
-1.73
(-9.446 to 6.648)
0.55
(-7.854 to 9.712)
6.Secondary Outcome
Title Serum Creatinine
Hide Description LS Mean Percentage Change (95% CI) from Baseline in Serum Creatinine
Time Frame From Baseline to 12 Weeks and 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
12 weeks Number Analyzed 30 participants 26 participants
-0.60
(-6.946 to 6.188)
3.44
(-3.636 to 11.025)
24 weeks Number Analyzed 27 participants 24 participants
1.93
(-4.743 to 9.078)
0.02
(-6.945 to 7.504)
7.Secondary Outcome
Title Serum Cystatin C
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
12 weeks Number Analyzed 30 participants 26 participants
3.252
(-1.3402 to 8.0581)
0.114
(-4.6520 to 5.1187)
24 weeks Number Analyzed 27 participants 24 participants
5.412
(0.5212 to 10.5418)
3.951
(-1.1612 to 9.3279)
8.Secondary Outcome
Title Serum High Sensitivity C-reactive Protein
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
12 weeks Number Analyzed 30 participants 26 participants
35.863
(4.5883 to 76.4884)
11.665
(-15.6408 to 47.8091)
24 weeks Number Analyzed 27 participants 24 participants
-8.002
(-29.9761 to 20.8680)
9.793
(-17.8132 to 46.6716)
9.Secondary Outcome
Title Clinical Assessments
Hide Description Change from Baseline in Diastolic and Systolic Blood Pressure
Time Frame From Baseline to 12 Weeks and 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mm/Hg
Diastolic BP, mmHg Baseline Number Analyzed 32 participants 28 participants
74.7  (9.83) 77.8  (11.91)
Diastolic BP, mmHg 12 weeks (Change from baseline) Number Analyzed 29 participants 25 participants
1.6  (11.02) -0.2  (9.51)
Diastolic BP, mmHg 24 weeks (Change from baseline) Number Analyzed 28 participants 25 participants
2.0  (8.53) 1.7  (12.05)
Systolic BP, mmHg Baseline Number Analyzed 32 participants 28 participants
136.4  (15.13) 138.5  (16.34)
Systolic BP, mmHg 12 weeks (Change from baseline) Number Analyzed 29 participants 25 participants
-0.8  (19.00) -3.2  (15.48)
Systolic BP, mmHg 24 weeks (Change from baseline) Number Analyzed 28 participants 25 participants
0.4  (9.75) -0.6  (17.78)
10.Secondary Outcome
Title MRI Variables - LV Mass/End-diastolic Volume
Hide Description Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame From Baseline to 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: g/mL
0.049  (0.1445) 0.053  (0.1202)
11.Secondary Outcome
Title MRI Variables - Kidney Cortex T2 Star - BOLD MRI
Hide Description Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame From Baseline to 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: ms
-1.46  (6.511) -1.67  (6.440)
12.Secondary Outcome
Title MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume
Hide Description Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame From Baseline to 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mL
LV End-diastolic Volume (mL) (CFB) Number Analyzed 18 participants 15 participants
-5.39  (27.458) -4.93  (20.665)
LV End-systolic Volume (mL) (CFB) Number Analyzed 18 participants 15 participants
1.33  (14.106) -2.48  (10.703)
LV Stroke Volume (mL) (CFB) Number Analyzed 18 participants 15 participants
-6.73  (15.923) -2.44  (12.458)
13.Secondary Outcome
Title MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain
Hide Description Change from baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame From Baseline to 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: % (change in percentage from baseline)
LV Ejection Fraction (%) (CFB) Number Analyzed 18 participants 15 participants
-2.08  (3.761) 0.59  (3.374)
Circumferential Strain (%) (CFB) Number Analyzed 18 participants 15 participants
-0.25  (2.321) -0.07  (2.192)
Longitudinal Strain (%) (CFB) Number Analyzed 19 participants 15 participants
0.29  (1.949) 0.53  (1.729)
Radial Strain (%) (CFB) Number Analyzed 18 participants 15 participants
-2.29  (7.136) 1.44  (8.109)
14.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
Hide Description Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame From Baseline to 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: s^-1
Diastolic Circumferential Strain Rate (s^-1) (CFB) Number Analyzed 18 participants 15 participants
-0.0496  (0.13769) -0.0384  (0.13791)
Diastolic Longitudinal Strain Rate (s^-1) (CFB) Number Analyzed 19 participants 15 participants
-0.0043  (0.10629) -0.0300  (0.16940)
Diastolic Radial Strain Rate (s^-1) (CFB) Number Analyzed 18 participants 15 participants
0.2348  (0.43676) 0.0201  (0.72927)
Systolic Circumferential Strain Rate (s^-1) (CFB) Number Analyzed 18 participants 15 participants
0.0115  (0.11314) -0.0743  (0.11616)
Systolic Longitudinal Strain Rate (s^-1) (CFB) Number Analyzed 19 participants 15 participants
0.0285  (0.08436) -0.0021  (0.08052)
Systolic Radial Strain Rate (s^-1) (CFB) Number Analyzed 18 participants 15 participants
-0.1917  (0.31833) 0.2516  (0.38049)
15.Secondary Outcome
Title MRI Variables - LV Mass
Hide Description Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time Frame From Baseline to 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: g
1.80  (7.532) 2.63  (9.994)
16.Other Pre-specified Outcome
Title Flow Mediated Dilatation (Reactive Hyperemia)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
12 weeks Change from Baseline Number Analyzed 22 participants 23 participants
0.8
(-10.59 to 12.24)
-5.9
(-17.04 to 5.29)
24 weeks Change from Baseline Number Analyzed 19 participants 19 participants
0.5
(-9.44 to 10.47)
-5.5
(-15.47 to 4.44)
17.Other Pre-specified Outcome
Title Urinalysis
Hide Description Changes in Urinalysis (CFB = Change from Baseline)
Time Frame From Baseline to 12 Weeks and 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline Protein, mg/dL Number Analyzed 28 participants 25 participants
72.01  (99.767) 65.74  (78.686)
Protein, mg/dL 12 weeks (CFB) Number Analyzed 25 participants 23 participants
-11.40  (65.896) -4.07  (71.047)
Protein, mg/dL 24 weeks (CFB) Number Analyzed 23 participants 22 participants
-16.73  (101.052) 11.40  (76.645)
Baseline Urine Albumin, mg/dL Number Analyzed 32 participants 28 participants
38.0907  (55.62178) 35.8905  (47.17446)
Urine Albumin, mg/dL 12 weeks (CFB) Number Analyzed 29 participants 26 participants
-9.4766  (35.73442) -0.3019  (45.81688)
Urine Albumin, mg/dL 24 weeks (CFB) Number Analyzed 27 participants 24 participants
-6.9482  (50.66844) 11.6049  (53.13042)
Baseline Urine Creatinine, mg/dL Number Analyzed 32 participants 28 participants
96.52  (51.570) 86.25  (46.189)
Urine Creatinine, mg/dL 12 weeks (CFB) Number Analyzed 29 participants 26 participants
5.06  (53.378) 12.95  (34.987)
Urine Creatinine, mg/dL 24 weeks (CFB) Number Analyzed 27 participants 24 participants
7.58  (55.930) 8.53  (36.430)
Baseline Urine Urate, mg/dL Number Analyzed 28 participants 25 participants
28.354  (12.0591) 23.960  (10.6862)
Urine Urate, mg/dL 12 weeks (CFB) Number Analyzed 25 participants 23 participants
-13.394  (13.2757) 3.560  (12.3875)
Urine Urate, mg/dL 24 weeks (CFB) Number Analyzed 23 participants 22 participants
-10.732  (16.4720) 2.294  (9.3407)
18.Other Pre-specified Outcome
Title Clinical Chemistry Values
Hide Description Changes in Clinical Chemistry Values (CFB = Change for Baseline)
Time Frame From Baseline to 12 Weeks and 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: pmol/L
Baseline Aldosterone, pmol/L Number Analyzed 31 participants 28 participants
134.58  (126.126) 95.11  (72.640)
Aldosterone, pmol/L 12 weeks (CFB) Number Analyzed 27 participants 26 participants
1.12  (118.622) 14.72  (72.485)
Aldosterone, pmol/L 24 weeks (CFB) Number Analyzed 24 participants 24 participants
9.14  (102.932) 38.14  (90.007)
Baseline NT-proBNP, pmol/L Number Analyzed 29 participants 27 participants
23.230  (22.6864) 15.866  (28.2147)
NT-proBNP, pmol/L 12 weeks (CFB) Number Analyzed 25 participants 25 participants
4.621  (31.1027) 1.556  (10.0140)
NT-proBNP, pmol/L 24 weeks (CFB) Number Analyzed 24 participants 21 participants
6.267  (19.0367) 15.866  (46.4392)
19.Other Pre-specified Outcome
Title Urinalysis
Hide Description Changes in Urinalysis (CFB = Change from Baseline)
Time Frame From Baseline to 12 Weeks and 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mg/g
Baseline Protein/Creatinine, mg/g Number Analyzed 27 participants 25 participants
945.56  (1457.714) 828.52  (987.671)
Protein/Creatinine, mg/g 12 weeks (CFB) Number Analyzed 22 participants 23 participants
-185.33  (366.340) -155.44  (584.772)
Protein/Creatinine, mg/g 24 weeks (CFB) Number Analyzed 21 participants 19 participants
-98.60  (397.778) 177.11  (1387.627)
20.Other Pre-specified Outcome
Title Clinical Chemistry Values
Hide Description Changes in Clinical Chemistry Values (CFB = Change for Baseline)
Time Frame From Baseline to 12 Weeks and 24 Weeks of Treatment
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: % hemoglobin bound to glucose
Baseline Hemoglobin A1C/Hemoglobin, % Number Analyzed 32 participants 27 participants
8.14  (1.913) 8.28  (2.025)
Hemoglobin A1C/Hemoglobin, % 12 weeks (CFB) Number Analyzed 30 participants 25 participants
0.20  (1.399) 0.13  (1.159)
Hemoglobin A1C/Hemoglobin, % 24 weeks (CFB) Number Analyzed 27 participants 21 participants
-0.14  (0.884) 0.22  (1.863)
21.Other Pre-specified Outcome
Title Baseline eGFR
Hide Description [Not Specified]
Time Frame Baseline
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[Not Specified]
Arm/Group Title Verinurad 9 mg+Febuxostat 80 mg Placebo
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m2
59.2  (25.25) 68.1  (23.15)
22.Other Pre-specified Outcome
Title Baseline UACR
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
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[Not Specified]
Arm/Group Title Verinurad 9 mg+Febuxostat 80 mg Placebo
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mg/g
459.05  (824.731) 411.55  (547.816)
23.Other Pre-specified Outcome
Title Baseline Serum Uric Acid (sUA)
Hide Description [Not Specified]
Time Frame Baseline
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[Not Specified]
Arm/Group Title Verinurad 9 mg+Febuxostat 80 mg Placebo
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mg/dL
7.51  (1.558) 7.02  (0.813)
24.Other Pre-specified Outcome
Title Baseline Serum Creatinine
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
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[Not Specified]
Arm/Group Title Verinurad 9 mg+Febuxostat 80 mg Placebo
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mg/dL
1.40  (0.595) 1.19  (0.362)
25.Other Pre-specified Outcome
Title Baseline Serum Cystatin-C
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Verinurad 9 mg+Febuxostat 80 mg Placebo
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mg/L
1.579  (0.5274) 1.313  (0.3532)
26.Other Pre-specified Outcome
Title Baseline Serum High-sensitivity C-reactive Protein
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Verinurad 9 mg+Febuxostat 80 mg Placebo
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 28
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.410  (0.3670) 0.358  (0.2506)
27.Other Pre-specified Outcome
Title Baseline MRI Variables - Kidney Cortex T2 Star
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 27
Mean (Standard Deviation)
Unit of Measure: ms
81.13  (12.995) 82.31  (11.625)
28.Other Pre-specified Outcome
Title Baseline MRI Variables - LV End-diastolic Volume
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: mL
161.47  (37.766) 161.50  (32.639)
29.Other Pre-specified Outcome
Title Baseline MRI Variables - LV Ejection Fraction
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: % (percentage of LV volume)
59.77  (7.869) 60.19  (6.134)
30.Other Pre-specified Outcome
Title Baseline MRI Variables - LV End-systolic Volume
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: mL
66.43  (26.089) 64.63  (17.977)
31.Other Pre-specified Outcome
Title Baseline MRI Variables - Circumferential Strain
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: % (change in percentage in LV dimension)
-14.10  (3.925) -15.37  (2.901)
32.Other Pre-specified Outcome
Title Baseline MRI Variables - Diastolic Circumferential Strain Rate
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: s^-1
0.6371  (0.24946) 0.7588  (0.21276)
33.Other Pre-specified Outcome
Title Baseline MRI Variables - Diastolic Longitudinal Strain Rate
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: s^-1
0.4833  (0.21090) 0.5258  (0.16476)
34.Other Pre-specified Outcome
Title Baseline MRI Variables - Diastolic Radial Strain Rate
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: s^-1
-2.3143  (1.08926) -2.7591  (1.05712)
35.Other Pre-specified Outcome
Title Baseline MRI Variables - Longitudinal Strain
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: % (change in percentage in LV dimension)
-12.07  (3.779) -12.21  (3.102)
36.Other Pre-specified Outcome
Title Baseline MRI Variables - Radial Strain
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: % (change in percentage in LV dimension)
43.47  (15.943) 46.45  (12.743)
37.Other Pre-specified Outcome
Title Baseline MRI Variables - Systolic Circumferential Strain Rate
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: s^-1
-0.7673  (0.19408) -0.7797  (0.12776)
38.Other Pre-specified Outcome
Title Baseline MRI Variables - Systolic Longitudinal Strain Rate
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: s^-1
-0.6278  (0.16784) -0.6552  (0.12734)
39.Other Pre-specified Outcome
Title Baseline MRI Variables - Systolic Radial Strain Rate
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: s^-1
2.1059  (0.66890) 2.1220  (0.58484)
40.Other Pre-specified Outcome
Title Baseline MRI Variables - LV Mass
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: g
110.27  (26.229) 110.82  (28.487)
41.Other Pre-specified Outcome
Title Baseline MRI Variables - LV Mass/End-diastolic Volume
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: g/mL
0.696  (0.1437) 0.687  (0.1163)
42.Other Pre-specified Outcome
Title Baseline MRI Variables - LV Stroke Volume
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 32 26
Mean (Standard Deviation)
Unit of Measure: mL
95.05  (19.327) 96.86  (21.286)
43.Other Pre-specified Outcome
Title Baseline Flow Mediated Dilatation (Reactive Hyperemia)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Capsule administered orally, once daily for 24 weeks
Capsule administered orally, once daily for 24 weeks
Overall Number of Participants Analyzed 29 26
Mean (Standard Deviation)
Unit of Measure: Units on a scale
60.4  (28.76) 60.6  (30.90)
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
Hide 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 (%) Affected / at Risk (%)
Total   0/32 (0.00%)      0/28 (0.00%)    
Hide Serious Adverse Events
Verinurad 9 mg+Febuxostat 80 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/32 (15.63%)      3/28 (10.71%)    
Cardiac disorders     
Acute Myocardial Infarction * 1  0/32 (0.00%)  0 1/28 (3.57%)  1
Cardiac Failure Congestive * 1  0/32 (0.00%)  0 1/28 (3.57%)  1
Gastrointestinal disorders     
Abdominal Distension * 1  1/32 (3.13%)  1 0/28 (0.00%)  0
Infections and infestations     
Bronchitis * 1  1/32 (3.13%)  1 0/28 (0.00%)  0
Injury, poisoning and procedural complications     
Rib Fracture * 1  1/32 (3.13%)  1 0/28 (0.00%)  0
Road Traffic Accident * 1  1/32 (3.13%)  1 0/28 (0.00%)  0
Investigations     
Troponin I Increased * 1  0/32 (0.00%)  0 1/28 (3.57%)  1
Musculoskeletal and connective tissue disorders     
Back Pain * 1  1/32 (3.13%)  1 0/28 (0.00%)  0
Renal and urinary disorders     
Acute Kidney Injury * 1  1/32 (3.13%)  1 0/28 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  1/32 (3.13%)  2 0/28 (0.00%)  0
Surgical and medical procedures     
Wound Drainage * 1  0/32 (0.00%)  0 1/28 (3.57%)  1
1
Term from vocabulary, MedDRA, version 20.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Verinurad 9 mg+Febuxostat 80 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/32 (28.13%)      2/28 (7.14%)    
Gastrointestinal disorders     
Diarrhoea * 1  4/32 (12.50%)  4 1/28 (3.57%)  1
Infections and infestations     
Nasopharyngitis * 1  2/32 (6.25%)  2 1/28 (3.57%)  1
Nervous system disorders     
Dizziness * 1  3/32 (9.38%)  3 0/28 (0.00%)  0
1
Term from vocabulary, MedDRA, version 20.0
*
Indicates events were collected by non-systematic assessment
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Fredrik Erlandsson, Global Clinical Lead
Organization: AstraZeneca R&D
Phone: +46317762365
EMail: Fredrik.Erlandsson@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03118739    
Other Study ID Numbers: D5495C00007
First Submitted: April 12, 2017
First Posted: April 18, 2017
Results First Submitted: July 15, 2019
Results First Posted: January 10, 2020
Last Update Posted: January 10, 2020