Open Label PK, PD and DDI of Dotinurad and Allopurinol in Gout Patients with Hyperuricemia

NCT06056570 | Completed Phase 1 FDA Drug

• 1 other identifier: UR1-DOT-103
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

A open label multi-center 3-period multidose, PK/PD and drug-drug interaction (DDI) study to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of 7 days of treatment with two doses of dotinurad monotherapy, and to evaluate the effect of dotinurad, as monotherapy and in combination with allopurinol, versus allopurinol monotherapy, on the PK of each, and to assess the additive PD effects on serum uric acid and urinary urate excretion in U.S. patients with gout and hyperuricemia

Conditions

Gout; Hyperuricemia

Outcome Measures

Primary Outcomes (4)

• Peak plasma concentrations (Cmax)

  To evaluate the Cmax of dotinurad 2mg, dotinturad 4mg, and allopurinol 300mg

  7 days

• Area under the plasma concentration versus time curve (AUC)

  To evaluate the AUC of dotinurad 2mg, dotinturad 4mg, and allopurinol 300mg

  7 days

• Time to maximum plasma concentration (Tmax)

  To evaluate the Tmax of dotinurad 2mg, dotinturad 4mg, and allopurinol 300mg

  7 days

• Terminal half life (T1/2)

  To evaluate the T1/2 of dotinurad 2mg, dotinturad 4mg, and allopurinol 300mg

  7 days

Study Arms (2)

dotinurad 2mg

EXPERIMENTAL

dotinurad 2mg q.d.

Drug: dontinurad; Drug: dotinurad + allopurinol; Drug: allopurinol

dotinurad 4mg

EXPERIMENTAL

dotinurad 4mg q.d.

Drug: dontinurad; Drug: dotinurad + allopurinol; Drug: allopurinol

Interventions

dontinurad DRUG

dotinurad alone

dotinurad 2mg; dotinurad 4mg

dotinurad + allopurinol DRUG

dotinurad + allopurinol 300mg

dotinurad 2mg; dotinurad 4mg

allopurinol DRUG

allopurinol 300 mg alone

dotinurad 2mg; dotinurad 4mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements.
• \. Patients with a diagnosis of gout based on American College of Rheumatology criteria (1997). Patients must fulfill at least 3 of the following, with one of those 3 being (i) hyperuricemia.
• More than one attack of acute arthritis
• Maximum inflammation developed within 1 day
• Monoarthritis attack
• Redness observed over joints
• First metatarsophalangeal joint painful or swollen
• Unilateral first metatarsophalangeal joint attack
• Unilateral tarsal joint attack
• Tophus (proven or suspected)
• Hyperuricemia.
• Asymmetric swelling within a joint on x-ray
• Subcortical cysts without erosions on x-ray
• Monosodium urate monohydrate microcrystals on joint fluid during attack
• Joint fluid culture negative for organisms during attack 3. The patient signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a patient fast for any laboratory evaluations.

You may not qualify if:

• \. The subject has current or historical evidence of any clinically significant disease or condition that might complicate the subject's participation, or, in the opinion of the Investigator, may place the subject at an unacceptable risk as a participant in this trial, may interfere with the interpretation of safety and/or tolerability data obtained in the trial, or may interfere with the absorption, distribution, metabolism, or excretion of the study drug.
• \. Patients with unstable angina, New York Heart Association Class III or IV heart failure, myocardial infarction, stroke, or deep venous thrombosis within 1 year prior to Day 1.
• \. QT interval corrected for heart rate according to Fridericia's formula \>470 msec in females and \>450 msec in males during Screening, confirmed by a repeat assessment.
• \. History of or presence of kidney stones. 5. History of or presence of malignancy in the last 5 years other than treated cutaneous basal or squamous cell carcinoma.
• \. Urological disorder not well controlled. 7. Peptic ulcer disease requiring active treatment. 8. Cannot safely discontinue uric acid-lowering medication 14 days prior to study start to 9 days after the last dose of study medication was administered.
• \. Surgery within the past 90 days prior to dosing as determined by the Principal Investigator to be clinically relevant.
• \. Use of agents that could confound serum uric acid analysis (eg, long-term use of salicylates \>100 mg or use of losartan).
• \. Patients with an acute gout flare during the screening period that had not resolved 1 week prior to the first dose of study.
• \. Hypersensitivity or intolerance to allopurinol, dotinurad or colchicine. 13. Positive for HLA-B\*58:01 allele 14. History or presence of alcoholism or chronic drug abuse within the past 2 years.
• \. Psychiatric disorder or social situation that prevents compliance with the protocol.
• \. Female patients who are pregnant or lactating. 17. Positive results for the urine drug /alcohol breath test/cotinine at check-in.
• \. Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg), Hepatitis C antibodies (HCV).
• \. Patient's semi-recumbent blood pressure is less than 90/40 mmHg or greater than 155/90 mmHg during Screening and Day -1.
• \. Stable dose of medications for long-term conditions such as diabetes, high cholesterol, hypertension, asthma, etc. are allowed (provided that the patient has been on a stable dose for at least 30 days prior to Screening and is not expected to require dose adjustment during the study through 7 days post study).
• \. Patient reports receiving a strong or moderate inhibitor of CYP3A4 or a P-gp inhibitor within 1 month prior to study drug dosing, due to potential interactions with colchicine.

Sponsors & Collaborators

• Urica Therapeutics Inc.: lead

Study Sites (4)

Clinical Research of West Florida

Clearwater, Florida, 33765, United States

Location

Panax Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Southwest Rheumatology Research

Mesquite, Texas, 75150, United States

Location

Endeavor Clinical Trials

San Antonio, Texas, 78240, United States

Location

MeSH Terms

Conditions

Gout; Hyperuricemia

Interventions

dotinurad; Allopurinol

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 28, 2023
• Study Start: October 4, 2023
• Primary Completion: June 27, 2024
• Study Completion: July 9, 2024
• Last Updated: January 28, 2025

Record last verified: 2025-01

Locations

US (4)