What Is Dotinurad?
Dotinurad is a drug currently under investigation in clinical trials, primarily for conditions associated with elevated uric acid levels in the body. It is administered orally, typically as an over-encapsulated tablet containing the active drug substance. While the specific mechanism of action is not detailed in the provided trial descriptions, its development focuses on managing conditions like gout and hyperuricemia. Dotinurad has been studied in a total of 7 clinical trials, with 3 trials currently recruiting participants and 3 completed. These studies have enrolled approximately 1,697 participants since the first trial began in August 2021, with the latest trial projected to conclude in April 2026. Clinical trials are evaluating dotinurad for its safety and effectiveness, sometimes comparing it with other treatments such as allopurinol or febuxostat. Key sponsors involved in the development of dotinurad include Crystalys Therapeutics and Eisai Co., Ltd.
Uses and Conditions Under Study
Dotinurad is being investigated across several conditions, primarily focusing on those related to elevated uric acid levels. A total of 7 clinical trials are exploring its potential uses.
- Uric Acid-Related Conditions: Dotinurad is extensively studied for conditions characterized by high uric acid. These include Gout, a type of arthritis caused by uric acid crystal buildup in joints (studied in 4 trials); Hyperuricemia, the presence of abnormally high uric acid in the blood (studied in 1 trial); and Tophaceous Gout, a severe form of gout involving uric acid crystal deposits (tophi), also studied in 1 trial. Additionally, one trial addresses both hyperuricemia or gout. Dotinurad aims to help manage these conditions by potentially reducing uric acid levels.
- Hypertension: One trial is investigating dotinurad in patients with Hypertension (high blood pressure). The rationale for studying dotinurad in hypertension may be related to potential links between uric acid levels and cardiovascular health, though specific details on this connection are not provided in the trial descriptions.
- Healthy Volunteers: One trial involves Healthy Volunteers. These studies are typically conducted early in drug development to assess the drug's safety, how it is absorbed, distributed, metabolized, and excreted in the body (pharmacokinetics), and how it affects the body (pharmacodynamics) in individuals without the target disease.
Dosing
Dotinurad is administered orally, primarily in the form of over-encapsulated tablets. The dosage forms studied include dotinurad alone, as well as comparisons with placebo, allopurinol, and febuxostat.
In clinical trials, various strengths and dosing regimens have been investigated for adult participants:
- Starting Dose: Some studies initiate treatment with a dose of 0.5 mg once daily.
- Maintenance Doses: The dose may then be gradually increased to a maintenance dose. Common maintenance doses studied include 2 mg once daily and 4 mg once daily. Specific trials have explored dotinurad 2 mg maintenance and dotinurad 4 mg maintenance.
- Single and Multiple Doses: Studies have also included cohorts investigating single doses of dotinurad and multiple doses of dotinurad to understand its effects over time.
The specific dosage and regimen for dotinurad would be determined by a healthcare provider based on the individual's condition and response to treatment. No investigational pediatric doses are detailed in the provided trial information.
Side Effects
No specific side effect data for Dotinurad was provided in the clinical trial results. Therefore, a comprehensive list of side effects cannot be presented at this time.
Clinical Trial Results
Clinical trials evaluated the effectiveness of Dotinurad in reducing serum uric acid (SUA) levels in participants with gout, comparing it to febuxostat. The primary study, NCT05007392, measured changes in SUA levels and the proportion of patients achieving target SUA levels over 24 weeks.
Reduction in Serum Uric Acid Levels
In the study, Dotinurad demonstrated a significant reduction in SUA levels from baseline. The mean reduction in SUA levels for patients taking Dotinurad ranged from 2.70 mg/dL to 5.05 mg/dL across various time points up to 24 weeks. This compared to a mean reduction of 2.60 mg/dL to 3.62 mg/dL for patients taking febuxostat.
The mean percentage reduction in SUA levels also showed favorable results for Dotinurad, ranging from 27.43% to 51.47%. For comparison, patients on febuxostat experienced mean percentage reductions ranging from 26.43% to 37.06%.
Achieving Target SUA Levels
A key measure of efficacy was the percentage of participants who achieved a target SUA level of 6.0 mg/dL or less. At Week 24, 73.6% of participants treated with Dotinurad reached this target, significantly outperforming febuxostat, where 38.1% of participants achieved the same goal.
Looking at earlier time points, at Week 12, 55.5% of patients on Dotinurad achieved an SUA level of 6.0 mg/dL or less, compared to 50.5% on febuxostat. Over the course of the study, the percentage of participants achieving this target with Dotinurad generally increased, reaching as high as 84.7% at Week 24 in one measurement, compared to 52.8% for febuxostat at the same time point.
Currently Recruiting Trials
Dotinurad is currently being investigated in several clinical trials for its potential to manage gout and hyperuricemia. These studies aim to understand how effectively dotinurad can lower serum uric acid levels and its impact on related conditions.
One ongoing Phase 3 study, NCT07089888, is evaluating dotinurad against allopurinol in adult participants with tophaceous gout. This trial, sponsored by Crystalys Therapeutics, seeks to determine dotinurad's efficacy in reducing serum uric acid at Week 24. The study plans to enroll approximately 250 participants.
Another Phase 3 trial, NCT07089875, also sponsored by Crystalys Therapeutics, compares dotinurad with allopurinol in a broader population of adult participants with hyperuricemia associated with gout. This study will assess the efficacy of dotinurad at 2 mg and 4 mg maintenance dosages in lowering serum uric acid at Week 24. This trial aims to enroll around 500 participants.
A Phase 4 study, NCT06834230, sponsored by Saga University, is investigating the effect of dotinurad in patients who have hyperuricemia complicated by hypertension. This study will compare dotinurad's impact on the cardio-ankle vascular index (CAVI) against febuxostat. This trial targets an enrollment of 360 participants.
Where to Participate
Opportunities to participate in dotinurad clinical trials are available across a wide geographic area. Studies are currently recruiting at 89 sites located in 82 cities across 28 states.
Top recruiting locations include:
- Chicago, Illinois (4 sites)
- Hialeah, Florida (4 sites)
- Houston, Texas (4 sites)
- San Antonio, Texas (4 sites)
- Tucson, Arizona (3 sites)
- Birmingham, Alabama (3 sites)
- Evansville, Indiana (2 sites)
- Atlanta, Georgia (2 sites)
- Indianapolis, Indiana (2 sites)
- Pomona, California (2 sites)
To be eligible for these studies, participants must generally be between the ages of 18 and 75 years. All genders are welcome, but these trials are not open to healthy volunteers or children.
Development Timeline
The clinical development of dotinurad began with its first trial initiated in August 2021. Since then, the drug has progressed through various stages of research, with the latest trial expected to conclude in April 2026. A total of seven clinical trials have been conducted or are ongoing, involving a combined enrollment of 1,697 participants.
Early development saw dotinurad explored for conditions such as IBS-C and hyperphosphatemia. Over time, the focus expanded, and the pipeline evolved to address conditions like Hypertension, Hyperuricemia, Hyperuricemia or Gout, and Tophaceous Gout.
The journey has involved several key sponsors, including Crystalys Therapeutics, Eisai Co., Ltd., Saga University, and Urica Therapeutics Inc., each contributing to the understanding of dotinurad's potential. The drug has advanced through Phase 1, Phase 1/Phase 2, Phase 2, Phase 3 (three trials), and Phase 4 studies, demonstrating a comprehensive progression through the clinical research process.