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Verinurad

Phase 2

Chronic Kidney Disease | Small molecule | Nephrology |AstraZeneca PLC|Last Updated: Mar 27, 2023

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials3
Total Enrollment881
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03990363A Study of Verinurad and Allopurinol in Patients With Chronic Kidney Disease and HyperuricaemiaPHASE2 COMPLETED 861Jul 23, 2019Nov 22, 2021Mar 2, 2023165 United States, Czechia +10
NCT04532918Pharmacokinetics of Verinurad and Allopurinol in Combination With Cyclosporine and Rifampicin in Healthy VolunteersPHASE1 COMPLETED 14Sep 10, 2020Nov 23, 2020Mar 27, 20231 Germany
NCT03836599A Study to Assess the Safety and Pharmacokinetics of Verinurad and Allopurinol in Asian and Chinese SubjectsPHASE1 COMPLETED 6Jan 16, 2019Apr 26, 2019May 13, 20191 United States
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Study Endpoints
Primary Endpoints
Urinary Albumin to Creatinine Ratio (uACR) (mg/g) Change From Baseline at 6 Months (Visit 8), Repeated Measures Mixed Model (MMRM)
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8)

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.

Geometric Mean Ratio of Maximum Observed Plasma Peak Concentration (Cmax) for Verinurad
Days 1 to 5 (pre-dose and post-dose)

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.

Geometric Mean Ratio of Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Verinurad
Days 1 to 5 (pre-dose and post-dose)

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.

Geometric Mean Ratio of Area Under the Plasma Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUClast) for Verinurad
Days 1 to 5 (pre-dose and post-dose)

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.

Number of participants with adverse events
From screening up to Follow-up visit/Early discontinuation visit (EDV) (7-14 Days Post-last PK Sample)

To assess the safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.

Number of participants with abnormal findings in electrocardiography (ECG)
From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)

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.

Number of participants with abnormal pulse rate
From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)

To assess abnormal pulse rate as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.

Number of participants with abnormal hematology
From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)

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.

Number of participants with abnormal blood pressure (systolic and diastolic)
From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)]

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.

Number of participants with abnormal physical examination
From screening up to Follow-up visit/EDV (7-14 Days Post-last PK sample)]

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.

Number of participants with abnormal electrolytes
From screening up to Follow-up visit/EDV (7-14 Days Post-last PK smaple)]

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.

Number of participants with abnormal hemoglobin (Hb)
From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)

To assess Hb as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.

Number of participants with abnormal hematocrit
From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)

To assess hematocrit as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.

Number of participants with abnormal Mean corpuscular volume (MCV)
From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)

To assess MCV as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.

Number of participants with abnormal mean corpuscular hemoglobin (MCH)
From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)

To assess MCH as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.

Number of participants with abnormal mean corpuscular hemoglobin concentration (MCHC)
From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)

To assess MCHC as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.

Number of participants with abnormal clinical chemistry
From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)

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.

Number of participants with abnormal urinalysis.
From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)

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.

Secondary Endpoints
Urinary Albumin to Creatinine Ratio (uACR) (mg/g) Change From Baseline at 12 Months (Visit 10), Repeated Measures Mixed Model (MMRM)
Baseline to 12 months (Visit 10); analysis at 12 months (Visit 10)
Serum Uric Acid (sUA) (mg/dL) Change From Baseline at 6 Months (Visit 8), Repeated Measures Mixed Model (MMRM)
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8)
Serum Uric Acid (sUA) Change From Baseline at 12 Months (Visit 10), Repeated Measures Mixed Model (MMRM)
Baseline to 12 months (Visit 10); analysis at 12 months (Visit 10)
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
High DoseEXPERIMENTALHigh Dose (mg) (verinurad/allopurinol) Step 1 - titration\_ 3/100 Step 2 - titration\_ 7.5/200 Step 3 - target dose\_ 12/300
Intermediate DoseEXPERIMENTALIntermediate Dose (mg) verinurad/allopurinol Step 1 - titration\_ 3/100 Step 2 - titration\_ 7.5/200 Step 3 - target dose\_ 7.5/300
Low DoseEXPERIMENTALLow 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)EXPERIMENTALStep 1 - titration\_0/100 Step 2 - titration\_0/200 Step 3 - target dose\_0/300
Placebo (0/0 mg)PLACEBO_COMPARATORPlacebo (mg) in 3 steps\_0/0
Verinurad + allopurinolEXPERIMENTALThe subjects will receive single oral dose of verinurad 7.5 mg and allopurinol 300 mg under fasted condition.
Verinurad + allopurinol + cyclosporineEXPERIMENTALThe subjects will receive single oral dose of verinurad 7.5 mg, allopurinol 300 mg and cyclosporine 600 mg under fasted condition.
Verinurad + allopurinol + rifampicinEXPERIMENTALThe subjects will receive single oral dose of verinurad 7.5 mg, allopurinol 300 mg and rifampicin 600 mg under fasted condition.
24 mg Verinurad+300 mg allopurinolEXPERIMENTALDuring 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 allopurinolEXPERIMENTALDuring 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.
PlaceboPLACEBO_COMPARATORDuring Run-in Period, participants in cohort 1 will receive placebo matching allopurinol capsule once daily from Day -7 to Day -1. During treatment period, participants in cohort 1 will receive placebo matching allopurinol capsule and placebo matching verinurad capsule once daily from Day 1 to Day 7.
Interventions
NameTypeDescription
VerinuradDRUGStudy treatments will be titrated in 3 steps for target low dose (3 mg), intermediate dose ( 7.5 mg) and High Dose (12 mg) Verinurad. As per Protocol Version 5.0, Patients from 3 mg dose will be switched to 24 mg at visit 9
AllopurinolDRUGStudy treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol
Placebo for VerinuradDRUGMatching Capsule
Placebo for AllopurinolDRUGMatching tablet
CyclosporineDRUGThe subjects will receive single oral dose of soft capsule cyclosporine 600 mg on Day 1 of treatment period 2 under fasted condition.
RifampicinDRUGThe subjects will receive single oral dose of film coated tablets rifampicin 600 mg on Day 1 of treatment period 3 under fasted condition.
PlaceboDRUGDuring Run-in Period, participants in cohort 1 will receive placebo matching allopurinol capsule once daily from Day -7 to Day -1. During treatment period, participants in cohort 1 will receive placebo matching allopurinol capsule and placebo matching verinurad capsule once daily from Day 1 to Day 7.
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Eligibility Criteria
Age Range18 Years — 130 Years
SexALL
Healthy VolunteersNo
Study Sites165

Inclusion Criteria: * The subject has given written informed consent prior to any mandatory study specific procedures, sampling, and analyses, and is able to understand and comply with all study procedures * Adult Patient ≥18 years of age with CKD for \>3 months. * Patients with background standard...

Countries:United StatesCzechiaFranceHungaryIsraelItalyMexicoPolandRomaniaSlovakiaSouth AfricaSpainGermany
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