Gout
Conditions
Keywords
Hyperuricemia
Brief summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of MBX-102 in combination with allopurinol compared to allopurinol alone when administered orally once a day for four weeks to gout patients with an inadequate hypouricemic response to allopurinol alone.
Interventions
DRUGArhalofenate
Arhalofenate 400 and 600 mgs over-encapsulated tablets once daily for 4 weeks or Allopurinol 300 mg once daily for 4 weeks
DRUGAllopurinol
Allopurinol 300 mg as active comparator
DRUGColchicine
0.6 mg colchicine daily as flare prophylaxis
DRUGPlacebo
Placebo
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Known gout patients (per criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout 1. Patients who have been taking at least 200 mg/day of allopurinol as the sole ULT for at least two weeks with a sUA of ≥ 6.5 mg/dL and ≤ 12 mg/dL at screening and ≥ 6.0 mg/dL and ≤ 12 mg/dL at Week -1 (Visit 2) randomization visit. -OR - 2. Patients who are not on ULT or are taking allopurinol \< 200 mg/day must have a sUA ≥ 8.0 mg/dL and ≤ 12 mg/dL at screening and ≥ 6.0 mg/dL and ≤ 12 mg/dL at Week -1 (Visit 2) randomization visit. 2. Male or female, 18-75 years of age at screening 3. All female patients must be surgically sterile or post-menopausal (at least 45 years of age with no history of menses for at least 2 years; or any age with no history of menses for at least six months and serum FSH ≥ 40 mIU/mL) or have a partner who has undergone vasectomy or must agree to use two medically accepted methods of contraception including a barrier method (see the list in Appendix 4) for the entire duration of the study unless she reports complete sexual abstinence. 4. Female patients must not be pregnant or lactating. 5. Male patients with a female partner of child-bearing potential must agree to use condoms or the partner must use a medically acceptable method of contraception for the entire duration of the study. 6. Estimated creatinine clearance (CrCl) by Cockcroft-Gault method ≥ 60 mL/min at screening 7. Serum creatinine value ≤ 1.1 mg/dL in females and ≤ 1.3 mg/dL in males 8. Liver function tests ≤ 1.5X ULN for AST, ALT and T-bilirubin, ≤ 2X ULN for ALP, ≤ 3X ULN for GGT; and ≤ 3X ULN for CK 9. All other clinical laboratory parameters must be within normal limits or considered not clinically significant for participation in this study. 10. Electrocardiogram (ECG) must be normal, or if abnormal, considered not clinically significant for participation in this study. 11. Systolic blood pressure ≤ 160 mm Hg and diastolic blood pressure ≤ 90 mm Hg; known hypertensive patients controlled with medications other than thiazide diuretics (blood pressure \[BP\] reading as above) may be included
Exclusion criteria
1. Treatment with any ULT other than allopurinol (e.g., probenecid, benzbromarone, febuxostat, or pegloticase) within 30 days of the Screening Visit 2. Known or suspected secondary hyperuricemia (e.g. due to myeloproliferative disorder, or organ transplant) 3. Diagnosis of xanthinuria 4. History of documented or suspected kidney stones 5. Known infection with HIV or history of viral hepatitis type B or C 6. History of illicit drug or alcohol abuse within 1 year of screening 7. History of significant pulmonary disease, upper GI bleeding, documented peptic ulcer disease (unless known H. pylori infection treated successfully without recurrence), or nephrotic syndrome within three years of screening 8. History of stroke, TIA, acute MI, congestive heart failure (NYHA Class II-IV), angina pectoris, coronary intervention procedure (including but not limited to angioplasty, stent placement, coronary revascularization), lower extremity bypass procedure, systemic or intracoronary fibrinolytic therapy within five years of screening 9. Malignancy (except treated basal cell carcinoma) within five years of screening 10. BMI \> 42 kg/m2 11. Current or expected requirement for anticoagulant therapy (except for aspirin ≤ 325 mg/day) 12. Rheumatoid arthritis or other autoimmune disease requiring ongoing treatment 13. Current or expected treatment with potent CYP3A4 inhibitors (See Appendix 6), cytotoxic agents (azathioprine, mercaptopurine, cyclosporine, cyclophosphamide, etc.), ranolazine, digoxin, theophylline, sulphonylureas, thiazolidinediones, diuretics, atypical antipsychotic agents, ampicillin, amoxicillin or phenytoin 14. Chronic treatment with NSAIDs (use to treat acute flares are permitted). 15. Current or expected treatment with systemic corticosteroids (except topical, ophthalmic, intra-articular, or inhaled at a dose \< 1600 μg/day) other than to treat acute flare 16. Known hypersensitivity to allopurinol, colchicine, or aspirin 17. Treatment with any other investigational therapy within the 30 days prior to screening, or patients who received at least one dose of study drug while enrolled in any previous or concomitant MBX-102 trial 18. Any other condition that compromises the ability of the patient to provide informed consent or to comply with the objectives and procedures of this protocol, as judged by the investigator and/or medical monitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Uric Acid | Percent change from baseline in serum uric acid at Week 4 | Percent change from baseline in serum uric acid in Per Protocol population |
Countries
Canada, Georgia, United States
Participant flow
Pre-assignment details
Upon completion of screening all patients will enter into a 3-week run-in/stabilization period starting at Week -3 (Visit 1). During this phase, all patients will take allopurinol 300 mg once daily. In addition, patients will be given colchicine 0.6 mg once daily until the final study visit as prophylaxis to prevent potential gout flares.
Participants by arm
| Arm | Count |
|---|---|
| Arhalofenate 400 mg Arhalofenate 400 mg plus allopurinol 300 mg | 35 |
| Arhalofenate 600 mg Arhalofenate 600 mg plus allopurinol 300 mg | 32 |
| Placebo Placebo plus Allopurinol 300 mg | 33 |
| Total | 100 |
Baseline characteristics
| Characteristic | Arhalofenate 400 mg | Arhalofenate 600 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 10.9 | 50.6 years STANDARD_DEVIATION 10.2 | 50.4 years STANDARD_DEVIATION 11 | 51.4 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 35 Participants | 32 Participants | 32 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 35 | 6 / 32 | 9 / 33 |
| serious Total, serious adverse events | 0 / 35 | 0 / 32 | 0 / 33 |
Outcome results
Primary
Serum Uric Acid
Percent change from baseline in serum uric acid in Per Protocol population
Time frame: Percent change from baseline in serum uric acid at Week 4
Population: Per Protocol population (all randomized patients who received at least 1 dose of blinded study drug, had at least 1 post-treatment evaluation, had not violated any major entry criterion likely to confound an efficacy analysis and had not deviated significantly from the protocol between enrollment and study completion).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arhalofenate 400 mg | Serum Uric Acid | -16.0 percent change | Standard Deviation 20.9 |
| Arhalofenate 600 mg | Serum Uric Acid | -9.9 percent change | Standard Deviation 17.1 |
| Placebo | Serum Uric Acid | -9.5 percent change | Standard Deviation 19 |