Gout
Conditions
Brief summary
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
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.
Interventions
DRUGPlacebo
Placebo twice daily from Day 1 to Week 12
DRUGAC-201
AC-201 CR tablet 100 mg twice daily from Day 1 to Week 12
DRUGFebuxostat
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
Sponsors
TWi Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female age 20 to 65 years, inclusive. 2. 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. 3. 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
1. Use of allopurinol, febuxostat, benzbromarone, probenecid, or sulfinpyrazone within 2 weeks prior to screening. 2. Occurrence of a gouty arthritis flare within 1 week prior to screening or during the screening period through baseline. 3. Use of colchicine within 1 week prior to screening. 4. Use of Glucocorticoids, NSAIDs or COX-2 inhibitors within 1 week prior to screening. 5. Allergy, contraindication, or intolerance to febuxostat. 6. Severe renal impairment. 7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration \>2 times the upper limit of laboratory normal range (\>2x ULN) at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 mg/dL | 8 weeks |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo plus Febuxostat
Placebo: Placebo twice daily from Day 1 to Week 12
Febuxostat: 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 | 60 |
| AC-201 AC-201 CR tablet plus Febuxostat
AC-201: AC-201 CR tablet 100 mg twice daily from Day 1 to Week 12
Febuxostat: 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 | 67 |
| Total | 127 |
Baseline characteristics
| Characteristic | Placebo | Total | AC-201 |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 13.1 | 47.4 years STANDARD_DEVIATION 12.3 | 47.3 years STANDARD_DEVIATION 11.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 60 Participants | 127 Participants | 67 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 60 Participants | 127 Participants | 67 Participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Male | 59 Participants | 121 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 67 |
| other Total, other adverse events | 29 / 60 | 43 / 67 |
| serious Total, serious adverse events | 0 / 60 | 0 / 67 |
Outcome results
Primary
Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 mg/dL
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 mg/dL | 33 Participants |
| AC-201 | Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 mg/dL | 43 Participants |