Evaluate the PK, PD, and Safety of Arhalofenate in Combination With Febuxostat for Hyperuricemia in Patients With Gout

NCT02252835 | Completed Phase 2

• 1 other identifier: CB102-21426
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate pharmacokinetics, pharmacodynamics, safety and potential for drug-drug interaction of arhalofenate when combined with febuxostat in adult population with gout.

Conditions

Gout; Hyperuricemia

Outcome Measures

Primary Outcomes (7)

• Proportion of patients achieving a target sUA < 6.0, < 5.0, < 4.0, and < 3.0 mg/dL on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg

  Day 29

• Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg

  Day 29

• Absolute and percent reduction in sUA from baseline on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg

  Day 29

• AUC(0-t) of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination

  Days 14, 28, and 42

• AUC(0-tau) of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination

  Days 14, 28, and 42

• Tmax of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination

  Days 14, 28, and 42

• Cmax of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination

  Days 14, 28, and 42

Secondary Outcomes (11)

• Proportion of patients achieving a target sUA < 6.0, < 5.0, < 4.0, and < 3.0 mg/dL on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg

  Day 29

• Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg

  Day 29

• Absolute and percent reduction in sUA from baseline on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg

  Day 29

• Proportion of patients achieving a target sUA < 6.0, < 5.0, < 4.0, and < 3.0 mg/dL on Day 22 after treatment with arhalofenate 800 mg and febuxostat 40 mg, and with arhalofenate 600 mg and febuxostat 80 mg

  Day 22

• Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 22 after treatment with arhalofenate 800 mg and febuxostat 40 mg, and with arhalofenate 600 mg and febuxostat 80 mg

  Day 22

Other Outcomes (5)

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  Days 1 through 43

• Change in physical examination findings

  Days 1 through 43

• Change in vital signs and safety laboratory tests

  Days 1 through 43

Study Arms (2)

Arhalofenate with febuxostat (PK cohort)

EXPERIMENTAL

Drug: Arhalofenate; Drug: Febuxostat; Drug: Colchicine

Arhalofenate with febuxostat (non-PK cohort)

EXPERIMENTAL

Drug: Arhalofenate; Drug: Febuxostat; Drug: Colchicine

Interventions

Arhalofenate DRUG

800 mg once daily orally for four weeks

Arhalofenate with febuxostat (PK cohort)

Febuxostat DRUG

40 mg once daily orally for 1 week then up-titrated to 80 mg once daily orally for another three weeks

Arhalofenate with febuxostat (PK cohort)

Colchicine DRUG

0.6 mg daily

Arhalofenate with febuxostat (PK cohort); Arhalofenate with febuxostat (non-PK cohort)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient, 18 to 75 years of age, inclusive
• Known gout diagnosis (per criteria of the American Rheumatism Association)
• Has an sUA ≥ 7.5 mg/dL
• A female patient must be surgically sterile or post-menopausal (at least 45 years of age with no history of menses for at least two years), or must agree to use two medically accepted methods of contraception including a barrier method for the entire duration of study participation unless she reports compete sexual abstinence. A female patient must also not be pregnant or lactating
• Estimated creatinine clearance (eCrCl) ≥ 60 ml/min, as calculated by Cockcroft-Gault method
• ALT or AST ≤ 3 times upper limit of normal (ULN) or total bilirubin ≤ 2 times ULN (Gilbert's syndrome is permitted)
• All other clinical laboratory parameters must be within normal limits or considered not clinically significant
• ECG must be normal, or if abnormal, considered not clinically significant
• A patient who is taking a medication or agent (other than a ULT) known to influence sUA levels must be on a stable dose and regimen of the medication for at least two weeks prior to screening and must be willing to continue the same dose and regimen during study participation
• Expected to be able to tolerate a short course of oral NSAIDs and/or oral steroids as may be needed to treat a gout flare
• Must be able to swallow tablets

You may not qualify if:

• Treatment with any ULT (e.g., allopurinol, febuxostat, probenecid, or benzbromarone) within two weeks, or pegloticase within six months, prior to the sUA assessment at Day 1
• Occurrence of a gout flare that has not resolved within one week prior to Day 1
• Known or suspected secondary hyperuricemia (e.g., due to myeloproliferative disorder or organ transplant)
• Diagnosis of xanthinuria
• Fractional excretion of urate \> 10%
• History of documented or suspected kidney stones within five years prior to screening
• Known infection with the human immunodeficiency virus (HIV) or history of hepatitis B or C
• Recent use/abuse of an illicit drug as determined by a positive urine drug screen
• Uncontrolled hypertension that, in the opinion of the Investigator, would preclude participation in the study
• History of stroke, transient ischemic attack, acute myocardial infarction, congestive heart failure (NYHA class II - IV), angina pectoris, coronary intervention procedure, lower extremity bypass procedure, systemic or intracoronary fibrinolytic therapy within 5 years of screening
• History of cancer within five years of screening, with the following exceptions: adequately treated non-melanoma skin cancer, non-metastatic prostate cancer, or in situ cervical cancer
• Body mass index (BMI) \> 42 kg/m2
• Current or expected requirement for anticoagulant therapy, except for low dose (≤ 81 mg/day) aspirin, clopidogrel (Plavix) ≤ 75 mg/day, or prasugrel (Effient) ≤ 10 mg/day
• Use of any of the following within eight weeks prior to screening: potent CYP3A4 inhibitors, cytotoxic agents (including azathioprine, mercaptopurine, cyclosporine, cyclophosphamide, etc.), ranolazine, digoxin, theophylline, sulphonylureas, thiazolidinediones (e.g., rosiglitazone or pioglitazone), desipramine, atypical antipsychotic agents, loop diuretics, warfarin, or phenytoin
• Chronic treatment with NSAIDs that cannot be safely discontinued-term use of NSAIDs is permitted, e.g., when used to treat gout flares

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Vince & Associates Clinical Research

Overland Park, Kansas, 66212, United States

Location

Related Publications (1)

• Steinberg AS, Vince BD, Choi YJ, Martin RL, McWherter CA, Boudes PF. The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout. J Rheumatol. 2017 Mar;44(3):374-379. doi: 10.3899/jrheum.161062. Epub 2016 Dec 15.

  PMID: 27980008 DERIVED

MeSH Terms

Conditions

Gout; Hyperuricemia

Interventions

arhalofenate; Febuxostat; Colchicine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids

Study Officials

• Alexandra Steinberg, MD, PhD

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2014
• First Posted: September 30, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 17, 2015

Record last verified: 2015-03

Locations

US (1)