Open Label Safety/Efficacy Study of Arhalofenate in Combination With Febuxostat for Hyperuricemia in Gout Patients

Sponsor

CymaBay Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01416402

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

13.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether arhalofenate is safe and effective when dosed in combination with febuxostat in lowering serum uric acid in patients with gout.

Condition or Disease	Intervention/Treatment	Phase
Hyperuricemia Gout	Drug: Arhalofenate Drug: Febuxostat Drug: Colchicine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open-label Study to Evaluate the Safety and Efficacy of Arhalofenate (MBX-102) in Combination With Febuxostat for the Treatment of Hyperuricemia in Patients With Gout

Study Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Oct 1, 2011

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: Arhalofenate with febuxostat and colchicine	Drug: Arhalofenate 400 mg once daily orally for two weeks then up-titrated to 600 mg once daily orally for an additional two weeks Other Names: MBX-102 Drug: Febuxostat 80 mg once daily orally for 5 weeks Other Names: Uloric Drug: Colchicine Colchicine 0.6 mg daily as prophylaxis to prevent gout flares Other Names: Colcrys

Arm

Intervention/Treatment

Other: Arhalofenate with febuxostat and colchicine

Drug: Arhalofenate

400 mg once daily orally for two weeks then up-titrated to 600 mg once daily orally for an additional two weeks

Other Names:

MBX-102

Drug: Febuxostat

80 mg once daily orally for 5 weeks

Other Names:

Uloric

Drug: Colchicine

Colchicine 0.6 mg daily as prophylaxis to prevent gout flares

Other Names:

Colcrys

Outcome Measures

Primary Outcome Measures

Proportion of patients achieving sUA <6.0 mg/dL, <5.0 mg/dL, <4.0 mg/dL and <3.0 mg/dL at the end of combination treatment period with each of the doses of arhalofenate [36 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Known gout patient (per criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout in Appendix 3) with a serum uric acid value of at least 8.0 mg/dL at Screening Visit. Patients on allopurinol must agree to discontinue their existing therapy at Visit 1 through the entire duration of the study and must have a sUA value of at least 8.0 mg/dL after a minimum 2 week wash-out at Visit 2.
Male or female, 18-75 years of age at Screening Visit
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 6 months and serum FSH ≥ 40 mIU/mL) 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 report of complete sexual abstinence.
Female patients must not be pregnant or lactating
Male patients with a female partner of child-bearing potential must agree to use condom or the partner must use a medically acceptable method of contraception for the entire duration of the study.
Estimated CrCl ≥ 50 mL/min as calculated by the by Cockcroft-Gault method
Serum creatinine value must be ≤ 1.3 mg/dL in females and ≤ 1.4 mg/dL in males
Patients must have liver function tests (LFTs) ≤ 1.5X ULN for AST, ALT and T-bilirubin, ≤ 2X ULN for ALP, ≤ 3X ULN for GGT; CK ≤ 3X ULN
All other clinical laboratory parameters must be within normal limits or considered not clinically significant
Electrocardiogram (ECG) must be normal, or if abnormal, considered not clinically significant
Patients must have a systolic blood pressure ≤ 160 mm Hg and a diastolic blood pressure ≤ 95 mm Hg; known hypertensive patients controlled with medication other than diuretics (BP reading as above) may be included
Patients must agree to remain in-clinic for 37 days consecutively and agree to follow the study procedures as described in the protocol

Exclusion Criteria:

Treatment with any ULT other than allopurinol (e.g., probenecid, benzbromarone, febuxostat, or pegloticase) within two weeks of the Screening Visit
Known or suspected secondary hyperuricemia (e.g. due to myeloproliferative disorder, or organ transplant).
Diagnosis of xanthinuria
History of documented or suspected kidney stones
Known infection with the human immunodeficiency virus (HIV) or history of viral hepatitis type B or C
History of illicit drug or alcohol abuse within one year of Screening Visit
History of significant pulmonary disease, upper gastrointestinal (GI) bleeding, documented peptic ulcer disease (unless known H. pylori infection treated successfully without recurrence), or nephrotic syndrome within three years of Screening Visit
History of stroke, TIA, acute myocardial infarction (MI), congestive heart failure (CHF) (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 5 years of screening
Malignancy within five years of Screening Visit (except successfully treated basal cell carcinoma)
Body mass index (BMI) > 42 kg/m2
Current or expected requirement for anticoagulant therapy [except for low-dose (≤ 325 mg/day) aspirin and/or Plavix® 75 mg/day]
Rheumatoid arthritis or other autoimmune disease requiring ongoing treatment
Current or expected treatment with potent CYP3A4 inhibitors (See Appendix 6), cytotoxic agents (azathioprine, mercaptopurine, cyclosporine, cyclophosphamide, etc.), ranolazine, digoxin, theophyline, desipramine, sulphonylurea, thiazolidinedione, diuretics, atypical antipsychotic agents, or phenytoin
Chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs use to treat acute gout flares is permitted)
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 gout flares
Known hypersensitivity to colchicine or febuxostat
Treatment with any other investigational therapy within the 30 days prior to the Screening Visit, or patients who received at least one dose of blinded study medication while enrolled in any previous arhalofenate trial
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