Gout MedDRA version: 17.1 Level: PT Classification code 10018627 Term: Gout System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: ADENURIC®
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FEBUXOSTAT
CAS Number: 144060-53-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Menarini International Operations Luxembourg S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients 18 years and older; 2. History of gout, flare free in the 4 weeks prior to study entry 3. History of crystal (joint liquid) proven diagnosis or anamnestic diagnosis of gout according to Wallace et al. To be eligible a subjects has to present at least 6 out of the twelve clinical, laboratory, and X-ray phenomena listed below: 1. Maximum inflammation developed within 1 day 2. More than one attack of acute arthritis 3. Monoarticular arthritis attack 4. Redness observed over joints 5. First metatarsophalangeal (MTP) pain or swelling 6. Unilateral first MTP joint attack 7. Unilateral tarsal joint attack 8. Suspected or proven tophus 9. Hyperuricemia 10. Asymmetric swelling within a joint on a X-ray 11. Subcortical cysts without erosions on X-ray 12. Negative organisms on culture of joint fluid 4. Naive to ULT or previously treated with ULT, but with no ULT treatment in the last 1 month prior to study entry and only if reason for ULT interruption was not due to safety concerns. 5. Patients at study entry have elevated serum urate level> 8 mg/dl. 6. Overall CV risk based on the scoring proposed by the Joint Task Force of the European Society of Cardiology and other Societies on cardiovascular disease prevention in clinical practice between 5 and 15% (inclusive) as per protocol appendix 2. Patients with diabetes mellitus type 2 could be included in the study if their CV risk score is calculated as =7%. 7. Concomitant medications should be maintained stable during the last 2 weeks before randomization Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 122 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Severe chronic renal failure (creatinine clearance 2 times the upper limit of normal. 4. Diabetes mellitus type1 5. Life-threatening co-morbidity or with a significant medical condition and/or conditions that would interfere with the treatment, the safety or the compliance with the protocol 6. Diagnosis of, or receiving treatment for malignancy (excluding minor skin cancer) in the previous 5 years 7. Patients who have experienced either myocardial infarction or stroke 8. Patients with inflammatory based arthritis (e.g.: rheumatoid arthritis, etc.) 9. Patients with congestive heart failure, New York Heart Association (NYHA) Class III or IV 10. Patients with untreated/uncontrolled thyroid function 11. Patients with clinically severe peripheral arterial disease 12. Concomitant administration of one of the following: azathioprine, mercaptopurine, theophylline, meclofenamate, sulfinpyrazone, trimethoprim-sulfamethoxazole, cyclophosphamide, benzbromarone, pyrazinamide, captopril and enalapril (for Allopurinol), tegafur, pegloticase and tacrolimus. 13. Hypersensitivity to any of the active substance or to any of the excipients 14. Any contraindication to febuxostat or allopurinol (with reference to the summary of product characteristics). 15. Subject is unable to take either of the protocol-required gout flare prophylactic medications (NSAID or colchicine) due to contraindications or intolerance, e.g. hypersensitivity, active gastric ulcer disease, renal impairment and/or changes in liver enzymes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Pulse Wave Velocity;Secondary Objective: • Pulse Wave Analysis • Brain natriuretic peptide and in N-terminal prohormone of brain natriuretic peptide (BNP and NTproBNP) • Markers of inflammation (hsCRP, TNF-a, plasma fibrinogen) • Markers of endothelial activation (sVCAM, sICAM, vWF, e-selectine) • Oxidative stress parameters: MDA, MPO, Ox-LDL, PON1 and PON2 • sUA, eGFR, Serum creatinine and urine albumin to creatinine ratio • Lipid profile • Safety and tolerability ;Primary end point(s): Comparison of the effects of febuxostat and allopurinol on Pulse Wave Velocity (PWV) after 36 weeks of treatment. ;Timepoint(s) of evaluation of this end point: after 36 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Changes in BNP and NTproBNP values after 12, 24 and 36 weeks of treatment; • Changes in inflammation markers (hsCRP, TNF-a, sUA, and plasma fibrinogen) after 12, 24 and 36 weeks of treatment; • Changes in oxidative stress parameters [Malondialdehyde (MDA), Myeloperoxidase (MPO) Oxidized low-density lipoprotein (Ox-LDL), Paraoxonase 1 and 2 (PON1, PON2)] after 12, 24 and 36 weeks of treatment; • Changes in lipid profile after 12, 24 and 36 weeks of treatment; • Percentage of gout patients with a serum urate concentration of less than 6 mg/dl after 12, 24 and 36 weeks of treatment. • Time to achieve sUA target levels for patients stratified for sUA levels at baseline as follows: 8.1-8.8 mg/dl, 8.9-9.6 mg/dl, 9.7-10.3 mg/dl, 10.4-11.0 mg/dl, >11 mg/dl. • Changes in eGFR with CKD-EPI formula after 12, 24 and 36 weeks of treatment; • Changes in urine albumin excretion as evaluated by first morning urine albumin/creatinine ratio (mg/g) after 12, 24 and 36 weeks of treatment; • Percentage of patients above the sUA target levels at Week 12, Week 24 and Week 36 after having reached the sUA target levels at Week 2; • Tender and swollen joint count; • Pulse Wave Analysis (including modifications of PWV, arterial stiffness, central blood pressure and augmentation index) after 12, 24 and 36 weeks of treatment; • Changes in endothelial activation/adhesion markers (sVCAM, sICAM, vWF, e-selectine) after 12, 24 and 36 weeks of treatment (These parameters will be evaluated in a subset of patients enrolled in selected centres only) The following laboratory parameters will be performed in central lab: • BNP, NTproBNP • Markers of inflammation: hsCRP, TNF-a, plasma fibrinogen • Oxidative stress parameters: MDA, MPO, Ox-LDL, PON1, PON2 • Markers of endothelial activation/adhesion: sVCAM, sICAM, vWF, e-selectine • sUA, eGF, Serum creatinine and urine albumin to creatinine ratio • Lipid profile ;Timepoint(s) of evaluation of this end point: after 12, 24 and 3 | — |
Countries
Croatia, Germany, Hungary, Italy, Netherlands, Poland, Romania, Serbia
Contacts
Public ContactPaolo Fabrizzi
Menarini
Outcome results
None listed