Tumor Lysis Syndrome MedDRA version: 14.1 Level: PT Classification code 10045170 Term: Tumour lysis syndrome System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 14.1 Level: LLT Classification code 10045152 Term: Tumor lysis syndrome System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: ADENURIC
Product Name: Adenuric
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: FEBUXOSTAT
CAS Number: 144060-53-7
Concentration unit: mg milligram(s)
Concentration type: equal
Con
Sponsors
Menarini Ricerche S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female patients a. aged = 18 years, and b. scheduled for first cytotoxic chemotherapy cycle, regardless of the line of treatment, because of hematologic malignancies, and c. at intermediate or high risk of TLS (see Appendix II, section 13.2 of study protocol for risk stratification), and d. with sUA levels 1 months. 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 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Patients known to be hypersensitive to Febuxostat or Allopurinol or to any of the components of the formulations. 2. Patients with hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose-galactase malabsorption. 3. Patients with uncontrolled ischemic heart disease or congestive heart failure (CHF). 4. Pregnant or breast feeding women. 5. Patients with sUA levels = 10 mg/dL at randomization (Visit 1). 6. Patients receiving Febuxostat, Allopurinol or any other urate lowering therapy (e.g. Rasburicase, probenecid) within 30 days prior to randomization. 7. Patients receiving mercaptopurine and azathioprine within 14 days prior to randomization. 8. High risk patients NOT candidate to Allopurinol treatment. 9. Patients with severe renal insufficiency. 10. Patients with severe hepatic insufficiency. 11. Patients with diagnosis of LTLS or CTLS at randomization (Visit 1). 12. Patients with any serious concomitant illness which, in the opinion of the Investigator, is incompatible with the protocol. 13. Patients receiving any other investigational agent within 30 days prior to randomization (Visit 1).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to compare the efficacy of Febuxostat with Allopurinol, in terms of sUA level control and preservation of renal function after seven days of treatment (Day 8) starting from 2 days prior to chemotherapy (Day 1).;Primary end point(s): The primary efficacy analysis will be based on the following co-primary endpoints: • Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8) (AUC sUA 1-8). • Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8). ;Timepoint(s) of evaluation of this end point: from baseline (Day 1) to the evaluation visit (Day 8) ;Secondary Objective: The secondary objectives of this study are: •To compare the efficacy of Febuxostat with Allopurinol, in terms of: -maintenance of sUA levels < 7.5 mg/dL -occurrence of LTLS according to Cairo-Bishop criteria (see study protocol Appendix I, section 13.1) -occurrence of CTLS according to Cairo-Bishop criteria (see study protocol Appendix I, section 13.1) •To compare the safety of Febuxostat with Allopurinol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints are: • Assessment of treatment responder rate, where treatment response is defined as the maintenance of sUA = 7.5 mg/dL from the start of chemotherapy (Day 3) to the evaluation visit (Day 8); treatment failure is defined as the presence of two or more consecutive values of sUA missing or > 7.5 mg/dL. The assessment will be based on the central laboratory result. • Assessment of LTLS, from start of chemotherapy (Day 3) to the evaluation visit (Day 8) based on local laboratory results. According to Cairo-Bishop definition LTLS is defined by the presence of 2 or more laboratory abnormalities including: a 25% increase or levels above normal for serum uric acid, potassium, and phosphate or a 25% decrease or levels below normal for calcium. For details, please refer to appendix 13.1.of the study protocol. • Assessment of CTLS, from start of chemotherapy (Day 3) to the evaluation visit (Day 8). According to Cairo-Bishop definition, CTLS is defined by the presence of LTLS in addition to 1 or more of the following significant clinical complications: renal insufficiency, cardiac arrhythmias, sudden death and seizures. The grade of CTLS is defined by the maximal grade of the clinical manifestation. For details, please refer to appendix 13.1.of the study protocol. ;Timepoint(s) of evaluation of this end point: from start of chemotherapy (Day 3) to the evaluation visit (Day 8) | — |
Countries
Brazil, Croatia, Czech Republic, France, Germany, Hungary, Italy, Poland, Romania, Russian Federation, Serbia, Spain, Ukraine
Contacts
Public ContactClinical Research CorporateDirector
Menarini Ricerche S.p.A.
Outcome results
None listed