Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Verinurad · 6 trials · 4 indications
Mean change from baseline in peak VO2 at Week 32 between the treatment groups was compared using change from baseline (i.e., week 32 value - baseline value) as the dependent variable, treatment as the independent variable and baseline peak VO2 included as covariate. H0: Difference in mean change from baseline in peak VO2 (verinurad + allopurinol vs placebo) = 0 Ha: Difference in mean change from baseline in peak VO2 (verinurad + allopurinol vs placebo) ≠ 0 A hierarchical test sequence was used for the confirmatory analysis of the primary and secondary objectives in order to address the issue of multiple testing and control the Type I error rate at an overall two-sided 0.05 level. Since this was the first test in the hierarchical test sequence and endpoint was not rejected at a two-sided 0.05 level, the testing sequence did not continue.
Analyses of change from baseline in uACR at 6 months (Visit 8) focused on: * High dose vs Placebo * High dose and Inter. dose combined vs Allopurinol alone * Inter. dose vs Placebo * Low dose vs Placebo * High dose vs Allopurinol * Inter. dose vs Allopurinol * Low dose vs Allopurinol * Allopurinol vs Placebo For High dose and Inter. dose combined the 2 categories merged forming 1 new temporary category.
Change from baseline in peak UA excretion during the first 8 hours on Day 7 of treatment to assess the effects of intensive UA lowering therapy with verinurad, febuxostat and dapagliflozin. Urine sample was collected in hourly intervals, and the highest amount of UA excreted in any interval was designated as peak UA excretion for each patient and treatment period.
Cmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
AUClast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
AUCτ assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad Cmax ratio of geometric mean of test treatment (verinurad+allopurinol with \[cyclosporine or rifampicin\], relative to reference treatment (verinurad+allopurinol alone) in each treatment period.
Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad AUCinf ratio of geometric means of test treatment, relative to reference treatment in each treatment period.
Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad AUClast ratio of geometric means of test treatment, relative to reference treatment in each treatment period.
Assessment of the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of International Council for Harmonisation Guideline E14 and associated Questions and Answers \[ICH E14 Q\&A\]), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF analysis. A linear mixed-effect concentration-QTcF model was used as the primary analysis. This is a result of the statistical model so it does not have values for every timepoint, it is just one set of numbers - summarizes data across all timepoints. No non-placebo-corrected QTcF data values were collected or could be obtained for each Arm/Group at Cmax of Verinurad.
To assess the safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess abnormal resting digital 12-lead electrocardiograms as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess abnormal pulse rate as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess white blood cell count (WBC), red blood cell count (RBC), neutrophils absolute count, lymphocytes absolute count, monocytes absolute count, eosinophils absolute count, basophils absolute count, platelets, and reticulocytes absolute count as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess abnormal blood pressure (systolic and diastolic) as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess safety and tolerability by assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
To assess serum level of sodium, potassium, calcium (total), and phosphate as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess Hb as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess hematocrit as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess MCV as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess MCH as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess MCHC as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
To assess the safety and tolerability profile of verinurad and allopurinol treatment in terms of the number of participants with abnormal clinical chemistry values. The laboratory variables to be measured are: bilirubin, creatinine, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cystatin C, gamma glutamyl transpeptidase, urea and uric acid.
To assess the safety and tolerability profile of verinurad and allopurinol treatment in terms of the number of participants with abnormal urinalysis values. The laboratory variables to be measured are: protein, glucose, blood, uric acid, pH, sodium, creatinine, and cystatin C.
| Arm | Type | Description |
|---|---|---|
| Verinurad 12 + allopurinol | EXPERIMENTAL | Dose \[mg\] verinurad/allopurinol: Step 1 - titration\_3/100 Step 2 - titration\_7.5/200 Step 3 - target dose 12/300 |
| Allopurinol alone | EXPERIMENTAL | Dose \[mg\] verinurad/allopurinol: Step 1 - titration\_0/100 Step 2 - titration\_0/200 Step 3 - target dose 0/300 |
| Placebo | PLACEBO_COMPARATOR | Placebo \[mg\] in 3 steps 0/0 |
| High Dose | EXPERIMENTAL | High Dose (mg) (verinurad/allopurinol) Step 1 - titration\_ 3/100 Step 2 - titration\_ 7.5/200 Step 3 - target dose\_ 12/300 |
| Intermediate Dose | EXPERIMENTAL | Intermediate Dose (mg) verinurad/allopurinol Step 1 - titration\_ 3/100 Step 2 - titration\_ 7.5/200 Step 3 - target dose\_ 7.5/300 |
| Low Dose | EXPERIMENTAL | Low Dose (mg) verinurad/allopurinol Step 1 - titration\_3/100 Step 2 - titration\_3/200 Step 3 - target dose\_3/300. As per Protocol Version 5.0, Patients from 3 mg dose will be switched to 24 mg at Visit 9. |
| Allopurinol alone (0/300 mg) | EXPERIMENTAL | Step 1 - titration\_0/100 Step 2 - titration\_0/200 Step 3 - target dose\_0/300 |
| Placebo (0/0 mg) | PLACEBO_COMPARATOR | Placebo (mg) in 3 steps\_0/0 |
| Treatment A | EXPERIMENTAL | Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin; |
| Treatment B | EXPERIMENTAL | Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin matched placebo |
| Verinurad + allopurinol | EXPERIMENTAL | The subjects will receive single oral dose of verinurad 7.5 mg and allopurinol 300 mg under fasted condition. |
| Verinurad + allopurinol + cyclosporine | EXPERIMENTAL | The subjects will receive single oral dose of verinurad 7.5 mg, allopurinol 300 mg and cyclosporine 600 mg under fasted condition. |
| Verinurad + allopurinol + rifampicin | EXPERIMENTAL | The subjects will receive single oral dose of verinurad 7.5 mg, allopurinol 300 mg and rifampicin 600 mg under fasted condition. |
| Treatment ABC | EXPERIMENTAL | Subjects will receive a single dose of all 3 treatments (A, B, and C) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
| Treatment BCA | EXPERIMENTAL | Subjects will receive a single dose of all 3 treatments (B, C, and A) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
| Treatment CAB | EXPERIMENTAL | Subjects will receive a single dose of all 3 treatments (C, A, and B) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
| Treatment ACB | EXPERIMENTAL | Subjects will receive a single dose of all 3 treatments (A, C, and B) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
| Treatment BAC | EXPERIMENTAL | Subjects will receive a single dose of all 3 treatments (B, A, and C) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
| Treatment CBA | EXPERIMENTAL | Subjects will receive a single dose of all 3 treatments (C, B and A) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
| 24 mg Verinurad+300 mg allopurinol | EXPERIMENTAL | During Run-in Period, participants will be dosed with 300 mg of allopurinol from Day -7 to Day -1. During the Treatment Period, participants will be administered 24 mg verinurad with 300 mg allopurinol once daily on Days 1 to 7. |
| 12 mg Verinurad+300 mg allopurinol | EXPERIMENTAL | During Run-in Period, participants will be dosed with 300 mg of allopurinol once daily from Day -7 to Day -1. During Treatment Period, participants will receive a single dose of 12 mg verinurad and 300 mg allopurinol on Day 1. No dosing will be done on Day 2. Participants will continue dosing on Day 3 and will be dosed once daily until Day 9. |
| Name | Type | Description |
|---|---|---|
| Verinurad | DRUG | The treatment will be titrated in 3 steps for target low dose (3 mg), intermediate dose (7.5 mg) and high dose (12mg) of verinurad. Drug: Allopurinol The treatment will be titrated in 3 steps. Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol. |
| Allopurinol | DRUG | Study treatments will be titrated in 3 steps: Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol |
| Placebo for verinurad | DRUG | Matching Capsule |
| Placebo for allopurinol | DRUG | Matching tablet |
| Febuxostat | DRUG | Randomized patients will receive orally once daily fixed dose of febuxostat in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo |
| Dapagliflozin | DRUG | Randomized patients will receive orally once daily fixed dose of dapagliflozin in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo |
| Dapagliflozin matched placebo | OTHER | Randomized patients will receive orally once daily fixed dose of dapagliflozin matched placebo in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo |
| Cyclosporine | DRUG | The subjects will receive single oral dose of soft capsule cyclosporine 600 mg on Day 1 of treatment period 2 under fasted condition. |
| Rifampicin | DRUG | The subjects will receive single oral dose of film coated tablets rifampicin 600 mg on Day 1 of treatment period 3 under fasted condition. |
| Placebo | DRUG | Randomized subjects will receive oral dose of placebo |
Inclusion Criteria: * Patient must be ≥ 40 years of age at the time of signing the ICF * Patients with hyperuricaemia defined as sUA level of \> 6 mg/dL. * Patients with documented diagnosis of symptomatic HFpEF according to all of the following criteria: 1. Have NYHA functional class II-III at ...
Verinurad is an investigational small molecule being studied for chronic kidney disease, hyperuricemia, asymptomatic hyperuricemia, and heart failure with preserved ejection fraction (HFpEF). It has been evaluated in Phase 2 clinical trials for these conditions, though it remains investigational and is not approved.
Verinurad is a uric acid lowering agent. It has been studied in combination with febuxostat and dapagliflozin to assess its effect on urinary excretion of uric acid in patients with asymptomatic hyperuricemia. Its mechanism involves reducing uric acid levels.
Verinurad is being developed by AstraZeneca PLC, which is listed on the stock exchange under the ticker AZN. The company has sponsored clinical trials of Verinurad across multiple countries, including the United States and Germany.
Verinurad has completed Phase 2 clinical trials for hyperuricemia, asymptomatic hyperuricemia, and heart failure with preserved ejection fraction. It has also completed a Phase 1 trial in healthy volunteers. The drug is investigational and has not been approved by regulatory authorities.
Verinurad has been studied in several completed trials. NCT03118739 evaluated it with febuxostat in patients with hyperuricemia and albuminuria. NCT03316131 assessed its effect on uric acid excretion with febuxostat and dapagliflozin. NCT04256629 examined its effect on heart electrical activity in healthy volunteers, and NCT04327024 studied it in heart failure with preserved ejection fraction.
Verinurad is also known as RDEA3170. In clinical trial NCT03316131, the study title refers to RDEA3170, which is the same drug as Verinurad. This alternative name may appear in older or related research documentation.