A Randomized, Double-Blind, Dose-Response Study of the Safety and Uric Acid Effects of Oral Ulodesine Added to Allopurinol in Subjects With Gout and Concomitant Moderate Renal Insufficiency

Study Overview
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Brief Summary
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To evaluate the overall safety and tolerability of ulodesine when combined with allopurinol in subjects with moderate renal insufficiency.

Official Title
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A Randomized, Double-Blind, Dose-Response Study of the Safety and Uric Acid Effects of Oral Ulodesine Added to Allopurinol in Subjects With Gout and Concomitant Moderate Renal Insufficiency

Conditions
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Gout, Hyperuricemia, Arthritis, Joint Disease, Renal Insufficiency

Intervention / Treatment
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* Drug: Placebo
* Drug: Ulodesine (BCX4208) 5 mg
* Drug: Ulodesine (BCX4208) 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 to < 70 years Have read and signed the Informed Consent Form Documented diagnosis of gout Documented moderate renal insufficiency Calculated creatinine clearance of ≥ 30 and < 60 mL/min Willing and able to take allopurinol 200 mg every day for the duration of the Treatment Female participants must be sexually abstinent for 4 weeks prior to Day 1 and continue abstinence for 4 weeks after completion of study drug, surgically sterile, postmenopausal,use oral contraceptives for three months prior to study drug dosing through 4 weeks after completion of study drug, an intrauterine device for 8 weeks prior to study drug dosing through 4 weeks after completion of study drug,double barrier contraception method for 4 weeks prior to study drug dosing through 4 weeks after completion of study drug administration Male participants must be sexually abstinent for 4 weeks prior to Day 1 and continue abstinence through 90 days after completion of study drug, be > 1 year postvasectomy, agree to use a condom with spermicide from the start of study drug dosing through 90 days after completion of study drug. Willing and able to provide authorization for the use and disclosure of personal health information in accordance with Health Insurance Portability and Accountability Act (HIPAA) Exclusion Criteria: Unable to tolerate allopurinol 200 mg every day Prior randomization in a clinical study with BCX4208 Unstable cardiac disease such as: unstable angina, symptomatic arrhythmia, signs or symptoms compatible with NYHA Class III or Class IV functional status for congestive heart failure or angina, history of long QT syndrome, or QTc interval < 350 msec or > 475 msec Poorly controlled hypertension History of severe renal insufficiency Alanine aminotransferase or aspartate aminotransferase values > 2.0 x upper limit of normal CD4+ cell counts by flow cytometry < 500 cells/mm3 Hemoglobin < 10 g/dL or > 18 g/dL (males) or < 10 g/dL or > 17 g/dL (females) White blood cell count < 3.7 x 109/L or > 11 x 109/L Female subjects who are pregnant, breastfeeding, or planning a pregnancy within the next 4 months Positive serology for hepatitis B surface antigen or hepatitis C antibody or HIV type 1 Immunocompromised due to illness or organ transplant Use of systemic immunosuppressive medications or disease-modifying antirheumatic drugs Use of azathioprine or 6-mercatopurine within 14 days of first dose of allopurinol Use of hydrochlorothiazide in doses > 50 mg per day Planned use of herbal or dietary supplements Recipient of any live or attenuated vaccine within 6 weeks of Screening Planned use of uric acid-lowering drugs other than allopurinol Use of systemic corticosteroids within 4 weeks prior to Day 1 Use of any investigational drug within 30 days prior to signing the ICF History of clinically significant and relevant drug allergies History of chronic or recurrent infections History of any type of cancer not successfully treated or in full remission for 12 months prior to Screening History of alcohol or drug abuse within the year prior to the signing of the ICF, or current evidence of substance dependence or abuse Use of other prohibited medications within the timeframes specified in the protocol Other medical conditions which, in the opinion of the Principal Investigator, would jeopardize the safety of the study subject

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo<br>Placebo + Allopurinol 200mg | Drug: Placebo<br>* Oral dose administered daily for 84 days.<br>|
| Experimental: Ulodesine (BCX4208) 5mg<br>BCX4208 5mg + Allopurinol 200 mg | Drug: Ulodesine (BCX4208) 5 mg<br>* Oral dose administered daily for 84 days.<br>|
| Experimental: Ulodesine (BCX4208) 10mg<br>BCX4208 10mg + Allopurinol 200mg | Drug: Ulodesine (BCX4208) 10 mg<br>* Oral dose administered daily for 84 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the overall safety and tolerability of ulodesine when combined with allopurinol in subjects with moderate renal insufficiency by assessment of percent change from baseline in CD4+ lymphocytes at Day 85. | Level of CD4+ lymphocytes to be measured at Day 85 compared to baseline. | 85 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gout, Hyperuricemia, Arthritis, Joint Disease, Allopurinol, Renal Insufficiency