Clinical efficacy and safety of dotinurad, a novel selective urate reabsorption inhibitor, in Japanese hyperuricemic patients with or without gout: an exploratory, randomized, multicenter, double-blind, placebo-controlled, parallel-group early phase 2 study.
Adult
Benzothiazoles
/ adverse effects
Double-Blind Method
Gout
/ drug therapy
Humans
Hyperuricemia
/ drug therapy
Japan
Male
Middle Aged
Organic Anion Transporters
/ antagonists & inhibitors
Organic Cation Transport Proteins
/ antagonists & inhibitors
Placebos
Uric Acid
/ blood
Uricosuric Agents
/ therapeutic use
Dotinurad
FYU-981
Gout
Hyperuricemia
Selective urate reabsorption inhibitor
URAT1 inhibitor
Journal
Clinical and experimental nephrology
ISSN: 1437-7799
Titre abrégé: Clin Exp Nephrol
Pays: Japan
ID NLM: 9709923
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
28
08
2019
accepted:
10
10
2019
pubmed:
23
11
2019
medline:
28
11
2020
entrez:
23
11
2019
Statut:
ppublish
Résumé
Dotinurad, a novel selective urate reabsorption inhibitor (SURI) that has a future potential for the treatment of hyperuricemia, reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1). We evaluated the efficacy and safety of dotinurad in hyperuricemic Japanese patients with or without gout. The study design was an exploratory, early phase 2 study that ran for 8 weeks. It was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, and performed in a dose escalation manner. There were four study arms consisting of dotinurad 1, 2, or 4 mg, and placebo. The primary endpoint was the percent change in serum uric acid level from the baseline to the final visit. The secondary endpoint was the percentage of patients achieving a serum uric acid level ≤ 6.0 mg/dL at the final visit. A total of 80 hyperuricemic patients with or without gout were enrolled and randomly assigned to the dotinurad or placebo groups. The mean percent change in serum uric acid level from the baseline to the final visit in the dotinurad 1, 2, 4 mg, and placebo groups was 37.03%, 50.91%, 64.37%, and 0.85%, respectively. The percentages of patients achieving a serum uric acid level ≤ 6.0 mg/dL at the final visit in each group were 75.0%, 89.5%, 95.2%, and none, respectively. The incidence of adverse events was comparable among all groups. Dotinurad has a substantial serum uric acid lowering effect in patients with hyperuricemia. No serious adverse event was found. CLINICALTRIALS. NCT02344862.
Sections du résumé
BACKGROUND
BACKGROUND
Dotinurad, a novel selective urate reabsorption inhibitor (SURI) that has a future potential for the treatment of hyperuricemia, reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1). We evaluated the efficacy and safety of dotinurad in hyperuricemic Japanese patients with or without gout.
METHODS
METHODS
The study design was an exploratory, early phase 2 study that ran for 8 weeks. It was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, and performed in a dose escalation manner. There were four study arms consisting of dotinurad 1, 2, or 4 mg, and placebo. The primary endpoint was the percent change in serum uric acid level from the baseline to the final visit. The secondary endpoint was the percentage of patients achieving a serum uric acid level ≤ 6.0 mg/dL at the final visit.
RESULTS
RESULTS
A total of 80 hyperuricemic patients with or without gout were enrolled and randomly assigned to the dotinurad or placebo groups. The mean percent change in serum uric acid level from the baseline to the final visit in the dotinurad 1, 2, 4 mg, and placebo groups was 37.03%, 50.91%, 64.37%, and 0.85%, respectively. The percentages of patients achieving a serum uric acid level ≤ 6.0 mg/dL at the final visit in each group were 75.0%, 89.5%, 95.2%, and none, respectively. The incidence of adverse events was comparable among all groups.
CONCLUSION
CONCLUSIONS
Dotinurad has a substantial serum uric acid lowering effect in patients with hyperuricemia. No serious adverse event was found. CLINICALTRIALS.
GOV IDENTIFIER
UNASSIGNED
NCT02344862.
Identifiants
pubmed: 31754882
doi: 10.1007/s10157-019-01802-w
pii: 10.1007/s10157-019-01802-w
pmc: PMC7066315
doi:
Substances chimiques
Benzothiazoles
0
Organic Anion Transporters
0
Organic Cation Transport Proteins
0
Placebos
0
SLC22A12 protein, human
0
Uricosuric Agents
0
Uric Acid
268B43MJ25
dotinurad
305EB53128
Banques de données
ClinicalTrials.gov
['NCT02344862']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
44-52Références
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