Dotinurad

Table of contents

• What is dotinurad?
• How does dotinurad work?
• Which conditions is dotinurad studied for?
• How is dotinurad given?
• What do the clinical trials show?
• What side effects are known?

What is dotinurad?

Dotinurad is a chemically synthesised small-molecule substance classified as a urate transporter inhibitor (ATC code M04AB06).^[3] It belongs to the group of antigout preparations that increase uric acid excretion.^[3] The substance is also known by the development code FYU-981 and the trade name Urece in Japan.^[2][3] In the product records of the EU trial, dotinurad has no marketing authorisation and is described as an investigational substance.^[1] The authorisation holder in the trial records is Crystalys Therapeutics, Inc.^[1]

How does dotinurad work?

Dotinurad works as a selective urate reabsorption inhibitor.^[2] It blocks the urate transporter 1 (URAT1), a protein expressed on the proximal renal tubules in the kidneys that normally reabsorbs uric acid back into the blood.^[2] By inhibiting URAT1, dotinurad reduces how much uric acid is taken back up, so more is excreted in the urine and serum uric acid levels fall.^[2][3]

Which conditions is dotinurad studied for?

• Hyperuricemia associated with gout — the EU Phase 3 trial studies dotinurad in adults with high uric acid levels linked to gout, a painful form of arthritis caused by urate crystals in joints.^[1]
• Hyperuricemia with or without gout — a published Japanese Phase 3 study compared dotinurad with benzbromarone in hyperuricemic patients who might or might not have gout.^[5]
• Chronic kidney disease with hyperuricemia — a retrospective study examined dotinurad in patients with chronic kidney disease and high uric acid levels.^[4]

How is dotinurad given?

Dotinurad is formulated as a tablet for oral use.^[1] In the EU trial, the product is described as dotinurad tablets and overencapsulated dotinurad tablets, indicating oral administration.^[1] The trial record does not report a specific dose, listing the dose as 0 mg, which means the dose was not reported in the register.^[1]

What do the clinical trials show?

One Phase 3 trial of dotinurad is authorised in the EU Clinical Trials Information System.^[1] The trial compares dotinurad with allopurinol, an established medicine for lowering uric acid, in adult participants with hyperuricemia associated with gout.^[1] It plans to enrol 500 participants.^[1]

The main outcome measure is the proportion of participants whose serum uric acid (sUA) level falls below 6.0 mg/dL at Week 24.^[1] Serum uric acid is the amount of uric acid dissolved in the blood; a level below 6.0 mg/dL is a common treatment target in gout.^[1] The trial is interventional, meaning participants receive a specific treatment rather than being observed only.^[1]

In a separate published Japanese Phase 3 study, dotinurad was compared with benzbromarone, another urate-lowering medicine, in a randomised, double-blind, parallel-group design.^[5] A retrospective study of 58 chronic kidney disease patients found that dotinurad decreased serum uric acid from 8.40 to 6.50 mg/dL over 3 months and improved the estimated glomerular filtration rate (eGFR), a measure of kidney function, from 33.9 to 36.2 mL/min/1.73 m².^[4] The same study reported no change in eGFR with febuxostat, a different urate-lowering drug.^[4]

What side effects are known?

The supplementary sources provided do not contain a detailed side-effect profile for dotinurad. The retrospective study in chronic kidney disease patients reported improvements in kidney function with dotinurad, but did not list adverse events.^[4] The Japanese Phase 3 study comparing dotinurad with benzbromarone is available as a peer-reviewed publication, but the excerpt provided does not include safety data.^[5] No side-effect information can therefore be reported from the sources given.