| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03990363 | A Study of Verinurad and Allopurinol in Patients With Chronic Kidney Disease and Hyperuricaemia | PHASE2 | COMPLETED | 861 | — | — | Jul 23, 2019 | Nov 22, 2021 | Mar 2, 2023 | 165 | United States, Czechia +10 |
| NCT04532918 | Pharmacokinetics of Verinurad and Allopurinol in Combination With Cyclosporine and Rifampicin in Healthy Volunteers | PHASE1 | COMPLETED | 14 | — | — | Sep 10, 2020 | Nov 23, 2020 | Mar 27, 2023 | 1 | Germany |
| NCT03836599 | A Study to Assess the Safety and Pharmacokinetics of Verinurad and Allopurinol in Asian and Chinese Subjects | PHASE1 | COMPLETED | 6 | — | — | Jan 16, 2019 | Apr 26, 2019 | May 13, 2019 | 1 | United States |
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.
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.
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 |
|---|---|---|
| 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 |
| 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. |
| 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. |
| Placebo | PLACEBO_COMPARATOR | During 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. |
| Name | Type | Description |
|---|---|---|
| Verinurad | DRUG | Study 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 |
| Allopurinol | DRUG | Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol |
| Placebo for Verinurad | DRUG | Matching Capsule |
| Placebo for Allopurinol | DRUG | Matching tablet |
| 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 | During 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. |
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...