Loading...
Rationale, design, demographics and baseline characteristics of the randomized, controlled, Phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia
Date
2021
Abstract
Background. Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad þ febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4–62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with chronic kidney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad þ allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia. Methods Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30–5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months. Conclusions This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.
Supervisor
Description
Publisher
Oxford Academic Press
Citation
Nephrology Dialysis Transplantation,August 2022 Volume 37, (8), Pages 1461–1471
Collections
Files
Loading...
Stack_2022_Rationale.pdf
Adobe PDF, 1.17 MB
Funding code
Funding Information
The SAPPHIRE study is sponsored by AstraZeneca. The sponsor was involved in the study design, writing of the article and the decision to submit the article for publicat
Sustainable Development Goals
External Link
Type
Article
Rights
https://creativecommons.org/licenses/by-nc-sa/4.0/