A Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Gout

Study Overview
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Brief Summary
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The study is designed to test the urate-lowering effect, safety, and tolerability of AC-201CR in an initial dosing period, followed by the addition of a ULT to test the efficacy and safety of the combination and prophylaxis of gout flares during ULT.

Detailed Description
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AC-201CR is a control released formulation of AC-201 that in previous clinical studies showed potential dual effects in both reducing serum uric acid (sUA) and gout flares. The mechanism of action of AC-201 includes the inhibition of the production and activity of caspase-1 and interleukin-1β (IL-1β), and selective inhibition of re-absorption transporters in the kidney. The goal of gout treatment is to reduce serum uric acid (sUA) concentrations below the urate solubility limit while avoiding acute gout flares. However, the initiation of urate-lowering therapy (ULT) increases the occurrence of acute gouty arthritis flares. IL-1β plays a key role in mediating this inflammatory response.

Official Title
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A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF AC-201 IN SUBJECTS WITH GOUT

Conditions
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Gout

Intervention / Treatment
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* Drug: Placebo
* Drug: AC-201
* Drug: Febuxostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age 20 to 65 years, inclusive. Meets ≥6 of the 12 American College of Rheumatology preliminary criteria (1977) for the classification of acute arthritis of primary gout (Appendix 2), OR have proven tophus or documented monosodium urate (MSU) crystals in the joint fluid. Serum uric acid ≥7.5 mg/dL and ≤10 mg/dL at screening with ≥1 gouty arthritis flare within one year prior to screening, OR serum uric acid ≥9 mg/dL and ≤10 mg/dL at screening with or without prior gout flares. Exclusion Criteria: Use of allopurinol, febuxostat, benzbromarone, probenecid, or sulfinpyrazone within 2 weeks prior to screening. Occurrence of a gouty arthritis flare within 1 week prior to screening or during the screening period through baseline. Use of colchicine within 1 week prior to screening. Use of Glucocorticoids, NSAIDs or COX-2 inhibitors within 1 week prior to screening. Allergy, contraindication, or intolerance to febuxostat. Severe renal impairment. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration >2 times the upper limit of laboratory normal range (>2x ULN) at screening.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo plus Febuxostat | Drug: Placebo<br>* Placebo twice daily from Day 1 to Week 12<br>* Other names: PBO;Drug: Febuxostat<br>* Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL<br>* Other names: ULT;|
| Experimental: AC-201<br>AC-201 CR tablet plus Febuxostat | Drug: AC-201<br>* AC-201 CR tablet 100 mg twice daily from Day 1 to Week 12<br>* Other names: AC-201 CR tablet;Drug: Febuxostat<br>* Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL<br>* Other names: ULT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 mg/dL |  | 8 weeks |