Albuminuria, Hyperuricemia, Type 2 Diabetes
Conditions
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).
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.
Interventions
DRUGVerinurad 9 mg+Febuxostat 80 mg
Capsule administered orally, once daily for 24 weeks
DRUGPlacebo
Capsule administered orally, once daily for 24 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Verinurad capsules/matching placebo capsules and febuxostat/matching placebo capsules with randomization code printed on each label
Intervention model description
Randomized, double-blind, double-dummy, placebo-controlled, parallel, independent groups, repeated measures, multi-center study
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Albumin to Creatinine Ratio (UACR) | From Baseline to 12 Weeks of Treatment | LS Mean Percentage Change (95% CI) from Baseline in UACR |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| eGFR | From Baseline to 12 Weeks and 24 Weeks of Treatment | LS Mean Percentage Change (95% CI) from Baseline in eGFR |
| Serum Creatinine | From Baseline to 12 Weeks and 24 Weeks of Treatment | LS Mean Percentage Change (95% CI) from Baseline in Serum Creatinine |
| 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 |
| 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 |
| Clinical Assessments | From Baseline to 12 Weeks and 24 Weeks of Treatment | Change from Baseline in Diastolic and Systolic Blood Pressure |
| 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) |
| 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) |
| 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) |
| 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) |
| MRI Variables - LV Mass | From Baseline to 24 Weeks of Treatment | Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline) |
| 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) |
| sUA | From Baseline to 12 Weeks and 24 Weeks of Treatment | LS Mean Percentage Change (95% CI) from Baseline in sUA |
Other
| Measure | Time frame | Description |
|---|---|---|
| Baseline MRI Variables - Circumferential Strain | Baseline | — |
| Baseline MRI Variables - Diastolic Circumferential Strain Rate | Baseline | — |
| Baseline MRI Variables - Diastolic Longitudinal Strain Rate | Baseline | — |
| Baseline MRI Variables - Diastolic Radial Strain Rate | Baseline | — |
| Baseline MRI Variables - Longitudinal Strain | Baseline | — |
| Baseline MRI Variables - Radial Strain | Baseline | — |
| Baseline MRI Variables - Systolic Circumferential Strain Rate | Baseline | — |
| Baseline MRI Variables - Systolic Longitudinal Strain Rate | Baseline | — |
| Baseline MRI Variables - Systolic Radial Strain Rate | Baseline | — |
| Baseline MRI Variables - LV Mass | Baseline | — |
| Baseline MRI Variables - LV Mass/End-diastolic Volume | Baseline | — |
| Baseline MRI Variables - LV Stroke Volume | Baseline | — |
| 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. |
| Urinalysis | From Baseline to 12 Weeks and 24 Weeks of Treatment | Changes in Urinalysis (CFB = Change from Baseline) |
| 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. |
| Clinical Chemistry Values | From Baseline to 12 Weeks and 24 Weeks of Treatment | Changes in Clinical Chemistry Values (CFB = Change for Baseline) |
| Baseline eGFR | Baseline | — |
| Baseline UACR | Baseline | — |
| Baseline Serum Uric Acid (sUA) | Baseline | — |
| Baseline Serum Creatinine | Baseline | — |
| Baseline Serum Cystatin-C | Baseline | — |
| Baseline Serum High-sensitivity C-reactive Protein | Baseline | — |
| Baseline MRI Variables - Kidney Cortex T2 Star | Baseline | — |
| Baseline MRI Variables - LV End-diastolic Volume | Baseline | — |
| Baseline MRI Variables - LV Ejection Fraction | Baseline | — |
| Baseline MRI Variables - LV End-systolic Volume | Baseline | — |
Countries
United States
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 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.
Participants by arm
| Arm | Count |
|---|---|
| Verinurad 9 mg+Febuxostat 80 mg Capsule administered orally, once daily for 24 weeks | 32 |
| Placebo Capsule administered orally, once daily for 24 weeks | 28 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Verinurad 9 mg+Febuxostat 80 mg | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 11 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 17 Participants | 33 Participants |
| Age, Continuous | 62.0 Years STANDARD_DEVIATION 9.51 | 60.9 Years STANDARD_DEVIATION 12.15 | 61.5 Years STANDARD_DEVIATION 10.74 |
| Body Mass Index | 32.00 kg/m2 STANDARD_DEVIATION 5.082 | 32.95 kg/m2 STANDARD_DEVIATION 4.699 | 32.44 kg/m2 STANDARD_DEVIATION 4.889 |
| estimated glomerular filtration rate (eGFR) eGFR<30 | 2 Participants | 1 Participants | 3 Participants |
| estimated glomerular filtration rate (eGFR) eGFR >=30 to <60 | 16 Participants | 9 Participants | 25 Participants |
| estimated glomerular filtration rate (eGFR) eGFR >=60 to <90 | 9 Participants | 12 Participants | 21 Participants |
| estimated glomerular filtration rate (eGFR) eGFR >=90 | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 7 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 21 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 170.57 cm STANDARD_DEVIATION 10.662 | 170.75 cm STANDARD_DEVIATION 9.117 | 170.65 cm STANDARD_DEVIATION 9.888 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 22 Participants | 15 Participants | 37 Participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 22 Participants | 20 Participants | 42 Participants |
| Weight | 93.72 kg STANDARD_DEVIATION 20.243 | 96.76 kg STANDARD_DEVIATION 19.561 | 95.14 kg STANDARD_DEVIATION 19.818 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 28 |
| other Total, other adverse events | 9 / 32 | 2 / 28 |
| serious Total, serious adverse events | 5 / 32 | 3 / 28 |
Outcome results
Primary
Urinary Albumin to Creatinine Ratio (UACR)
LS Mean Percentage Change (95% CI) from Baseline in UACR
Time frame: From Baseline to 24 Weeks of Treatment
Population: Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Urinary Albumin to Creatinine Ratio (UACR) | -38.40 Precent change |
| Placebo | Urinary Albumin to Creatinine Ratio (UACR) | 21.40 Precent change |
Primary
Urinary Albumin to Creatinine Ratio (UACR)
LS Mean Percentage Change (95% CI) from Baseline in UACR
Time frame: From Baseline to 12 Weeks of Treatment
Population: Number analyzed at 12 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Urinary Albumin to Creatinine Ratio (UACR) | -48.65 Precent change |
| Placebo | Urinary Albumin to Creatinine Ratio (UACR) | -15.31 Precent change |
90% CI: [-61.785, -3.814]
Primary
Urinary Albumin to Creatinine Ratio (UACR) Compared to Placebo
LS Mean Percentage Change (90% CI) from Baseline in UACR Compared to Placebo
Time frame: From Baseline to 24 Weeks of Treatment
Population: Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Urinary Albumin to Creatinine Ratio (UACR) Compared to Placebo | -49.26 Precent change |
| Placebo | Urinary Albumin to Creatinine Ratio (UACR) Compared to Placebo | NA Precent change |
Secondary
Clinical Assessments
Change from Baseline in Diastolic and Systolic Blood Pressure
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Assessments | Diastolic BP, mmHg 24 weeks (Change from baseline) | 2.0 mm/Hg | Standard Deviation 8.53 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Assessments | Systolic BP, mmHg Baseline | 136.4 mm/Hg | Standard Deviation 15.13 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Assessments | Systolic BP, mmHg 12 weeks (Change from baseline) | -0.8 mm/Hg | Standard Deviation 19 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Assessments | Diastolic BP, mmHg 12 weeks (Change from baseline) | 1.6 mm/Hg | Standard Deviation 11.02 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Assessments | Systolic BP, mmHg 24 weeks (Change from baseline) | 0.4 mm/Hg | Standard Deviation 9.75 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Assessments | Diastolic BP, mmHg Baseline | 74.7 mm/Hg | Standard Deviation 9.83 |
| Placebo | Clinical Assessments | Systolic BP, mmHg 24 weeks (Change from baseline) | -0.6 mm/Hg | Standard Deviation 17.78 |
| Placebo | Clinical Assessments | Diastolic BP, mmHg Baseline | 77.8 mm/Hg | Standard Deviation 11.91 |
| Placebo | Clinical Assessments | Diastolic BP, mmHg 12 weeks (Change from baseline) | -0.2 mm/Hg | Standard Deviation 9.51 |
| Placebo | Clinical Assessments | Systolic BP, mmHg Baseline | 138.5 mm/Hg | Standard Deviation 16.34 |
| Placebo | Clinical Assessments | Systolic BP, mmHg 12 weeks (Change from baseline) | -3.2 mm/Hg | Standard Deviation 15.48 |
| Placebo | Clinical Assessments | Diastolic BP, mmHg 24 weeks (Change from baseline) | 1.7 mm/Hg | Standard Deviation 12.05 |
Secondary
eGFR
LS Mean Percentage Change (95% CI) from Baseline in eGFR
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | eGFR | 12 weeks | 1.25 Percent change |
| Verinurad 9 mg+Febuxostat 80 mg | eGFR | 24 weeks | -1.73 Percent change |
| Placebo | eGFR | 12 weeks | -4.40 Percent change |
| Placebo | eGFR | 24 weeks | 0.55 Percent change |
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)
Time frame: From Baseline to 24 Weeks of Treatment
Population: Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Diastolic Radial Strain Rate (s^-1) (CFB) | 0.2348 s^-1 | Standard Deviation 0.43676 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Diastolic Circumferential Strain Rate (s^-1) (CFB) | -0.0496 s^-1 | Standard Deviation 0.13769 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Diastolic Longitudinal Strain Rate (s^-1) (CFB) | -0.0043 s^-1 | Standard Deviation 0.10629 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Systolic Circumferential Strain Rate (s^-1) (CFB) | 0.0115 s^-1 | Standard Deviation 0.11314 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Systolic Longitudinal Strain Rate (s^-1) (CFB) | 0.0285 s^-1 | Standard Deviation 0.08436 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Systolic Radial Strain Rate (s^-1) (CFB) | -0.1917 s^-1 | Standard Deviation 0.31833 |
| Placebo | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Systolic Longitudinal Strain Rate (s^-1) (CFB) | -0.0021 s^-1 | Standard Deviation 0.08052 |
| Placebo | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Diastolic Radial Strain Rate (s^-1) (CFB) | 0.0201 s^-1 | Standard Deviation 0.72927 |
| Placebo | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Systolic Circumferential Strain Rate (s^-1) (CFB) | -0.0743 s^-1 | Standard Deviation 0.11616 |
| Placebo | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Diastolic Circumferential Strain Rate (s^-1) (CFB) | -0.0384 s^-1 | Standard Deviation 0.13791 |
| Placebo | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Systolic Radial Strain Rate (s^-1) (CFB) | 0.2516 s^-1 | Standard Deviation 0.38049 |
| Placebo | MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate | Diastolic Longitudinal Strain Rate (s^-1) (CFB) | -0.0300 s^-1 | Standard Deviation 0.1694 |
Secondary
MRI Variables - Kidney Cortex T2 Star - BOLD MRI
Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time frame: From Baseline to 24 Weeks of Treatment
Population: Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - Kidney Cortex T2 Star - BOLD MRI | -1.46 ms | Standard Deviation 6.511 |
| Placebo | MRI Variables - Kidney Cortex T2 Star - BOLD MRI | -1.67 ms | Standard Deviation 6.44 |
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)
Time frame: From Baseline to 24 Weeks of Treatment
Population: Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain | Longitudinal Strain (%) (CFB) | 0.29 % (change in percentage from baseline) | Standard Deviation 1.949 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain | LV Ejection Fraction (%) (CFB) | -2.08 % (change in percentage from baseline) | Standard Deviation 3.761 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain | Radial Strain (%) (CFB) | -2.29 % (change in percentage from baseline) | Standard Deviation 7.136 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain | Circumferential Strain (%) (CFB) | -0.25 % (change in percentage from baseline) | Standard Deviation 2.321 |
| Placebo | MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain | Radial Strain (%) (CFB) | 1.44 % (change in percentage from baseline) | Standard Deviation 8.109 |
| Placebo | MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain | Circumferential Strain (%) (CFB) | -0.07 % (change in percentage from baseline) | Standard Deviation 2.192 |
| Placebo | MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain | LV Ejection Fraction (%) (CFB) | 0.59 % (change in percentage from baseline) | Standard Deviation 3.374 |
| Placebo | MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain | Longitudinal Strain (%) (CFB) | 0.53 % (change in percentage from baseline) | Standard Deviation 1.729 |
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)
Time frame: From Baseline to 24 Weeks of Treatment
Population: Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume | LV End-diastolic Volume (mL) (CFB) | -5.39 mL | Standard Deviation 27.458 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume | LV End-systolic Volume (mL) (CFB) | 1.33 mL | Standard Deviation 14.106 |
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume | LV Stroke Volume (mL) (CFB) | -6.73 mL | Standard Deviation 15.923 |
| Placebo | MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume | LV End-diastolic Volume (mL) (CFB) | -4.93 mL | Standard Deviation 20.665 |
| Placebo | MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume | LV End-systolic Volume (mL) (CFB) | -2.48 mL | Standard Deviation 10.703 |
| Placebo | MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume | LV Stroke Volume (mL) (CFB) | -2.44 mL | Standard Deviation 12.458 |
Secondary
MRI Variables - LV Mass
Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time frame: From Baseline to 24 Weeks of Treatment
Population: Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV Mass | 1.80 g | Standard Deviation 7.532 |
| Placebo | MRI Variables - LV Mass | 2.63 g | Standard Deviation 9.994 |
Secondary
MRI Variables - LV Mass/End-diastolic Volume
Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Time frame: From Baseline to 24 Weeks of Treatment
Population: Number analyzed at 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | MRI Variables - LV Mass/End-diastolic Volume | 0.049 g/mL | Standard Deviation 0.1445 |
| Placebo | MRI Variables - LV Mass/End-diastolic Volume | 0.053 g/mL | Standard Deviation 0.1202 |
Secondary
Serum Creatinine
LS Mean Percentage Change (95% CI) from Baseline in Serum Creatinine
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Serum Creatinine | 12 weeks | -0.60 Percent change |
| Verinurad 9 mg+Febuxostat 80 mg | Serum Creatinine | 24 weeks | 1.93 Percent change |
| Placebo | Serum Creatinine | 12 weeks | 3.44 Percent change |
| Placebo | Serum Creatinine | 24 weeks | 0.02 Percent change |
Secondary
Serum Cystatin C
LS Mean Percentage Change (95% CI) from Baseline in Serum Cystatin C
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Serum Cystatin C | 12 weeks | 3.252 Percent change |
| Verinurad 9 mg+Febuxostat 80 mg | Serum Cystatin C | 24 weeks | 5.412 Percent change |
| Placebo | Serum Cystatin C | 12 weeks | 0.114 Percent change |
| Placebo | Serum Cystatin C | 24 weeks | 3.951 Percent change |
Secondary
Serum High Sensitivity C-reactive Protein
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
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Serum High Sensitivity C-reactive Protein | 12 weeks | 35.863 Percent change |
| Verinurad 9 mg+Febuxostat 80 mg | Serum High Sensitivity C-reactive Protein | 24 weeks | -8.002 Percent change |
| Placebo | Serum High Sensitivity C-reactive Protein | 12 weeks | 11.665 Percent change |
| Placebo | Serum High Sensitivity C-reactive Protein | 24 weeks | 9.793 Percent change |
Secondary
sUA
LS Mean Percentage Change (95% CI) from Baseline in sUA
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | sUA | 12 weeks | -56.81 Percent change |
| Verinurad 9 mg+Febuxostat 80 mg | sUA | 24 weeks | -61.93 Percent change |
| Placebo | sUA | 12 weeks | 6.86 Percent change |
| Placebo | sUA | 24 weeks | 4.73 Percent change |
Other Pre-specified
Baseline eGFR
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline eGFR | 59.2 mL/min/1.73m2 | Standard Deviation 25.25 |
| Placebo | Baseline eGFR | 68.1 mL/min/1.73m2 | Standard Deviation 23.15 |
Other Pre-specified
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.
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with exam (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline Flow Mediated Dilatation (Reactive Hyperemia) | 60.4 Units on a scale | Standard Deviation 28.76 |
| Placebo | Baseline Flow Mediated Dilatation (Reactive Hyperemia) | 60.6 Units on a scale | Standard Deviation 30.9 |
Other Pre-specified
Baseline MRI Variables - Circumferential Strain
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Circumferential Strain | -14.10 % (change in percentage in LV dimension) | Standard Deviation 3.925 |
| Placebo | Baseline MRI Variables - Circumferential Strain | -15.37 % (change in percentage in LV dimension) | Standard Deviation 2.901 |
Other Pre-specified
Baseline MRI Variables - Diastolic Circumferential Strain Rate
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Diastolic Circumferential Strain Rate | 0.6371 s^-1 | Standard Deviation 0.24946 |
| Placebo | Baseline MRI Variables - Diastolic Circumferential Strain Rate | 0.7588 s^-1 | Standard Deviation 0.21276 |
Other Pre-specified
Baseline MRI Variables - Diastolic Longitudinal Strain Rate
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Diastolic Longitudinal Strain Rate | 0.4833 s^-1 | Standard Deviation 0.2109 |
| Placebo | Baseline MRI Variables - Diastolic Longitudinal Strain Rate | 0.5258 s^-1 | Standard Deviation 0.16476 |
Other Pre-specified
Baseline MRI Variables - Diastolic Radial Strain Rate
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Diastolic Radial Strain Rate | -2.3143 s^-1 | Standard Deviation 1.08926 |
| Placebo | Baseline MRI Variables - Diastolic Radial Strain Rate | -2.7591 s^-1 | Standard Deviation 1.05712 |
Other Pre-specified
Baseline MRI Variables - Kidney Cortex T2 Star
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Kidney Cortex T2 Star | 81.13 ms | Standard Deviation 12.995 |
| Placebo | Baseline MRI Variables - Kidney Cortex T2 Star | 82.31 ms | Standard Deviation 11.625 |
Other Pre-specified
Baseline MRI Variables - Longitudinal Strain
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Longitudinal Strain | -12.07 % (change in percentage in LV dimension) | Standard Deviation 3.779 |
| Placebo | Baseline MRI Variables - Longitudinal Strain | -12.21 % (change in percentage in LV dimension) | Standard Deviation 3.102 |
Other Pre-specified
Baseline MRI Variables - LV Ejection Fraction
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - LV Ejection Fraction | 59.77 % (percentage of LV volume) | Standard Deviation 7.869 |
| Placebo | Baseline MRI Variables - LV Ejection Fraction | 60.19 % (percentage of LV volume) | Standard Deviation 6.134 |
Other Pre-specified
Baseline MRI Variables - LV End-diastolic Volume
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - LV End-diastolic Volume | 161.47 mL | Standard Deviation 37.766 |
| Placebo | Baseline MRI Variables - LV End-diastolic Volume | 161.50 mL | Standard Deviation 32.639 |
Other Pre-specified
Baseline MRI Variables - LV End-systolic Volume
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - LV End-systolic Volume | 66.43 mL | Standard Deviation 26.089 |
| Placebo | Baseline MRI Variables - LV End-systolic Volume | 64.63 mL | Standard Deviation 17.977 |
Other Pre-specified
Baseline MRI Variables - LV Mass
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - LV Mass | 110.27 g | Standard Deviation 26.229 |
| Placebo | Baseline MRI Variables - LV Mass | 110.82 g | Standard Deviation 28.487 |
Other Pre-specified
Baseline MRI Variables - LV Mass/End-diastolic Volume
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - LV Mass/End-diastolic Volume | 0.696 g/mL | Standard Deviation 0.1437 |
| Placebo | Baseline MRI Variables - LV Mass/End-diastolic Volume | 0.687 g/mL | Standard Deviation 0.1163 |
Other Pre-specified
Baseline MRI Variables - LV Stroke Volume
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - LV Stroke Volume | 95.05 mL | Standard Deviation 19.327 |
| Placebo | Baseline MRI Variables - LV Stroke Volume | 96.86 mL | Standard Deviation 21.286 |
Other Pre-specified
Baseline MRI Variables - Radial Strain
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Radial Strain | 43.47 % (change in percentage in LV dimension) | Standard Deviation 15.943 |
| Placebo | Baseline MRI Variables - Radial Strain | 46.45 % (change in percentage in LV dimension) | Standard Deviation 12.743 |
Other Pre-specified
Baseline MRI Variables - Systolic Circumferential Strain Rate
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Systolic Circumferential Strain Rate | -0.7673 s^-1 | Standard Deviation 0.19408 |
| Placebo | Baseline MRI Variables - Systolic Circumferential Strain Rate | -0.7797 s^-1 | Standard Deviation 0.12776 |
Other Pre-specified
Baseline MRI Variables - Systolic Longitudinal Strain Rate
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Systolic Longitudinal Strain Rate | -0.6278 s^-1 | Standard Deviation 0.16784 |
| Placebo | Baseline MRI Variables - Systolic Longitudinal Strain Rate | -0.6552 s^-1 | Standard Deviation 0.12734 |
Other Pre-specified
Baseline MRI Variables - Systolic Radial Strain Rate
Time frame: Baseline
Population: Total number differs from Study totals due to subject non compliance with MRI (exam not completed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline MRI Variables - Systolic Radial Strain Rate | 2.1059 s^-1 | Standard Deviation 0.6689 |
| Placebo | Baseline MRI Variables - Systolic Radial Strain Rate | 2.1220 s^-1 | Standard Deviation 0.58484 |
Other Pre-specified
Baseline Serum Creatinine
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline Serum Creatinine | 1.40 mg/dL | Standard Deviation 0.595 |
| Placebo | Baseline Serum Creatinine | 1.19 mg/dL | Standard Deviation 0.362 |
Other Pre-specified
Baseline Serum Cystatin-C
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline Serum Cystatin-C | 1.579 mg/L | Standard Deviation 0.5274 |
| Placebo | Baseline Serum Cystatin-C | 1.313 mg/L | Standard Deviation 0.3532 |
Other Pre-specified
Baseline Serum High-sensitivity C-reactive Protein
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline Serum High-sensitivity C-reactive Protein | 0.410 mg/dL | Standard Deviation 0.367 |
| Placebo | Baseline Serum High-sensitivity C-reactive Protein | 0.358 mg/dL | Standard Deviation 0.2506 |
Other Pre-specified
Baseline Serum Uric Acid (sUA)
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline Serum Uric Acid (sUA) | 7.51 mg/dL | Standard Deviation 1.558 |
| Placebo | Baseline Serum Uric Acid (sUA) | 7.02 mg/dL | Standard Deviation 0.813 |
Other Pre-specified
Baseline UACR
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Baseline UACR | 459.05 mg/g | Standard Deviation 824.731 |
| Placebo | Baseline UACR | 411.55 mg/g | Standard Deviation 547.816 |
Other Pre-specified
Clinical Chemistry Values
Changes in Clinical Chemistry Values (CFB = Change for Baseline)
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | Baseline Aldosterone, pmol/L | 134.58 pmol/L | Standard Deviation 126.126 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | Aldosterone, pmol/L 12 weeks (CFB) | 1.12 pmol/L | Standard Deviation 118.622 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | Aldosterone, pmol/L 24 weeks (CFB) | 9.14 pmol/L | Standard Deviation 102.932 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | Baseline NT-proBNP, pmol/L | 23.230 pmol/L | Standard Deviation 22.6864 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | NT-proBNP, pmol/L 12 weeks (CFB) | 4.621 pmol/L | Standard Deviation 31.1027 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | NT-proBNP, pmol/L 24 weeks (CFB) | 6.267 pmol/L | Standard Deviation 19.0367 |
| Placebo | Clinical Chemistry Values | NT-proBNP, pmol/L 12 weeks (CFB) | 1.556 pmol/L | Standard Deviation 10.014 |
| Placebo | Clinical Chemistry Values | Baseline Aldosterone, pmol/L | 95.11 pmol/L | Standard Deviation 72.64 |
| Placebo | Clinical Chemistry Values | Baseline NT-proBNP, pmol/L | 15.866 pmol/L | Standard Deviation 28.2147 |
| Placebo | Clinical Chemistry Values | Aldosterone, pmol/L 12 weeks (CFB) | 14.72 pmol/L | Standard Deviation 72.485 |
| Placebo | Clinical Chemistry Values | NT-proBNP, pmol/L 24 weeks (CFB) | 15.866 pmol/L | Standard Deviation 46.4392 |
| Placebo | Clinical Chemistry Values | Aldosterone, pmol/L 24 weeks (CFB) | 38.14 pmol/L | Standard Deviation 90.007 |
Other Pre-specified
Clinical Chemistry Values
Changes in Clinical Chemistry Values (CFB = Change for Baseline)
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | Baseline Hemoglobin A1C/Hemoglobin, % | 8.14 % hemoglobin bound to glucose | Standard Deviation 1.913 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | Hemoglobin A1C/Hemoglobin, % 12 weeks (CFB) | 0.20 % hemoglobin bound to glucose | Standard Deviation 1.399 |
| Verinurad 9 mg+Febuxostat 80 mg | Clinical Chemistry Values | Hemoglobin A1C/Hemoglobin, % 24 weeks (CFB) | -0.14 % hemoglobin bound to glucose | Standard Deviation 0.884 |
| Placebo | Clinical Chemistry Values | Baseline Hemoglobin A1C/Hemoglobin, % | 8.28 % hemoglobin bound to glucose | Standard Deviation 2.025 |
| Placebo | Clinical Chemistry Values | Hemoglobin A1C/Hemoglobin, % 12 weeks (CFB) | 0.13 % hemoglobin bound to glucose | Standard Deviation 1.159 |
| Placebo | Clinical Chemistry Values | Hemoglobin A1C/Hemoglobin, % 24 weeks (CFB) | 0.22 % hemoglobin bound to glucose | Standard Deviation 1.863 |
Other Pre-specified
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.
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Flow Mediated Dilatation (Reactive Hyperemia) | 24 weeks Change from Baseline | 0.5 Units on a scale |
| Verinurad 9 mg+Febuxostat 80 mg | Flow Mediated Dilatation (Reactive Hyperemia) | 12 weeks Change from Baseline | 0.8 Units on a scale |
| Placebo | Flow Mediated Dilatation (Reactive Hyperemia) | 12 weeks Change from Baseline | -5.9 Units on a scale |
| Placebo | Flow Mediated Dilatation (Reactive Hyperemia) | 24 weeks Change from Baseline | -5.5 Units on a scale |
Other Pre-specified
Urinalysis
Changes in Urinalysis (CFB = Change from Baseline)
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Baseline Protein/Creatinine, mg/g | 945.56 mg/g | Standard Deviation 1457.714 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Protein/Creatinine, mg/g 12 weeks (CFB) | -185.33 mg/g | Standard Deviation 366.34 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Protein/Creatinine, mg/g 24 weeks (CFB) | -98.60 mg/g | Standard Deviation 397.778 |
| Placebo | Urinalysis | Baseline Protein/Creatinine, mg/g | 828.52 mg/g | Standard Deviation 987.671 |
| Placebo | Urinalysis | Protein/Creatinine, mg/g 12 weeks (CFB) | -155.44 mg/g | Standard Deviation 584.772 |
| Placebo | Urinalysis | Protein/Creatinine, mg/g 24 weeks (CFB) | 177.11 mg/g | Standard Deviation 1387.627 |
Other Pre-specified
Urinalysis
Changes in Urinalysis (CFB = Change from Baseline)
Time frame: From Baseline to 12 Weeks and 24 Weeks of Treatment
Population: Number analyzed at 12 and 24 weeks was less than the overall number analyzed due to missing observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Protein, mg/dL 24 weeks (CFB) | -16.73 mg/dL | Standard Deviation 101.052 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Baseline Urine Creatinine, mg/dL | 96.52 mg/dL | Standard Deviation 51.57 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Urine Albumin, mg/dL 12 weeks (CFB) | -9.4766 mg/dL | Standard Deviation 35.73442 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Urine Creatinine, mg/dL 12 weeks (CFB) | 5.06 mg/dL | Standard Deviation 53.378 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Protein, mg/dL 12 weeks (CFB) | -11.40 mg/dL | Standard Deviation 65.896 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Urine Creatinine, mg/dL 24 weeks (CFB) | 7.58 mg/dL | Standard Deviation 55.93 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Baseline Urine Urate, mg/dL | 28.354 mg/dL | Standard Deviation 12.0591 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Baseline Urine Albumin, mg/dL | 38.0907 mg/dL | Standard Deviation 55.62178 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Urine Urate, mg/dL 12 weeks (CFB) | -13.394 mg/dL | Standard Deviation 13.2757 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Urine Albumin, mg/dL 24 weeks (CFB) | -6.9482 mg/dL | Standard Deviation 50.66844 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Urine Urate, mg/dL 24 weeks (CFB) | -10.732 mg/dL | Standard Deviation 16.472 |
| Verinurad 9 mg+Febuxostat 80 mg | Urinalysis | Baseline Protein, mg/dL | 72.01 mg/dL | Standard Deviation 99.767 |
| Placebo | Urinalysis | Urine Urate, mg/dL 24 weeks (CFB) | 2.294 mg/dL | Standard Deviation 9.3407 |
| Placebo | Urinalysis | Baseline Protein, mg/dL | 65.74 mg/dL | Standard Deviation 78.686 |
| Placebo | Urinalysis | Protein, mg/dL 12 weeks (CFB) | -4.07 mg/dL | Standard Deviation 71.047 |
| Placebo | Urinalysis | Protein, mg/dL 24 weeks (CFB) | 11.40 mg/dL | Standard Deviation 76.645 |
| Placebo | Urinalysis | Baseline Urine Albumin, mg/dL | 35.8905 mg/dL | Standard Deviation 47.17446 |
| Placebo | Urinalysis | Urine Albumin, mg/dL 12 weeks (CFB) | -0.3019 mg/dL | Standard Deviation 45.81688 |
| Placebo | Urinalysis | Urine Creatinine, mg/dL 24 weeks (CFB) | 8.53 mg/dL | Standard Deviation 36.43 |
| Placebo | Urinalysis | Urine Albumin, mg/dL 24 weeks (CFB) | 11.6049 mg/dL | Standard Deviation 53.13042 |
| Placebo | Urinalysis | Baseline Urine Creatinine, mg/dL | 86.25 mg/dL | Standard Deviation 46.189 |
| Placebo | Urinalysis | Urine Creatinine, mg/dL 12 weeks (CFB) | 12.95 mg/dL | Standard Deviation 34.987 |
| Placebo | Urinalysis | Baseline Urine Urate, mg/dL | 23.960 mg/dL | Standard Deviation 10.6862 |
| Placebo | Urinalysis | Urine Urate, mg/dL 12 weeks (CFB) | 3.560 mg/dL | Standard Deviation 12.3875 |