Hematological malignancies at intermediate to high risk of Tumor Lysis Syndrome ( TLS) prevention. MedDRA version: 19.0 Level: PT Classification code 10045170 Term: Tumour lysis syndrome System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Adenuric® 120 mg
Product Name: Febuxostat
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FEBUXOSTAT
CAS Number: 144060-53-7
Concentration unit: mg milligram(s)
Concentration
Sponsors
Menarini Ricerche S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting ALL the following criteria will be eligible to enter the study: 1.male and female children of 6 to less than 12 years of age, adolescents of 12 to less than 18 years of age, and adults: a.scheduled for first cytotoxic chemotherapy cycle, regardless of the line of treatment, because of hematologic malignancies, and b.at intermediate or high risk for TLS, and c.with serum uric acid (sUA) levels 1 month. Are the trial subjects under 18? yes Number of subjects for this age range: 96 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Patients will not be eligible to participate in the study if they meet ANY of the following exclusion criteria: 1.patients known to be hypersensitive to febuxostat or to any components of the formulation; 2.patients with hereditary problems of galactose intolerance, the lapp lactase deficiency, or glucose-galactase malabsorption; 3.pregnant or breastfeeding women; 4.patients receiving febuxostat or any other urate-lowering therapy (e.g. allopurinol, rasburicase, probenecid) within 30 days prior to Visit 1 (Day 1); 5.patients receiving mercaptopurine and azathioprine within 14 days prior to Visit 1 (Day 1); 6.patients with severe renal insufficiency; 7.patients with severe hepatic insufficiency; 8.patients with diagnosis of Laboratory TLS (LTLS) or Clinical TLS (CTLS) at Visit 1 (Day 1). 9.Patients receiving any other investigational agent within 30 days prior to study Visit 1 (Day 1).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To assess the pharmacokinetics (PK) of febuxostat in paediatric patients (=6<18 years of age) and in adults suffering from hematological malignancies at intermediate to high risk of TLS. -To compare the febuxostat exposure in pediatric patients (=6<18 years of age) with the one achieved in adults administered with a dose of 120 mg/QD. ;Secondary Objective: -To compare the pharmacodynamics (PD) of febuxostat between pediatric patients (=6<18 years of age) and adults. -To evaluate and compare the PK/PD relationship of febuxostat in pediatric patients (=6<18 years of age) and adults. -To evaluate the safety of febuxostat between pediatric patients (=6<18 years of age) and adults. -To evaluate the occurrence of Laboratory TLS (LTLS) and Clinical TLS (CTLS) according to Cairo and Bishop Criteria -To assess the age-appropriate formulation acceptability in children. ;Primary end point(s): Pharmacokinetic endpoints derived from the study will include: ? Primary PK parameters: CL/F, Vd/F and Ka. ? Derived PK parameters: AUC and Cmax. ;Timepoint(s) of evaluation of this end point: Blood samples will be collected on Visits 2, 3, 4, 5, 6, 7 and 8 (i.e., after the first treatment administration and on each following visit until the Evaluation Visit). Four additional blood samples are required for each patient on Visit 7 (Day 7) at the selected sampling intervals: 0.5-2 hours, 2-4 hours, 4-6 hours and 6-8 hours post study drug intake. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacodynamic endpoint: 1. Area under the curve of sUA from baseline (Visit 1, Day 1) to the Evaluation Visit (Visit 8, Day 8) (AUC sUA 1-8) based on central laboratory results. PK/PD endpoint: 2.The PK/PD relationship will be evaluated based on sUA levels and febuxostat exposure. Clinical endpoints: 3. Incidence of Laboratory TLS (LTLS) from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8), based on local laboratory results. -Incidence and grading of Clinical TLS (CTLS) from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8) based on local laboratory results. Safety endpoints: 4.Incidence, severity (both through Mild/Moderate/Severe scale and NCI-CTCAE grade), seriousness and treatment causality of Treatment-Emergent Signs and Symptoms (TESS). -Frequency of clinically significant abnormalities in physical examination, safety laboratory tests, vital signs and 12 Lead ECG. -Change in PS according to Karnofsky/Lansky scales. 5. Acceptability assessment of the age-appropriate formulation only for children.;Timepoint(s) of evaluation of this end point: 1. Blood samples for sUA analysis will be performed from Visits 1 to 8 (i.e., before 1st drug intake, on each following visit until the Evaluation Visit). 2. PK/PD timepoints are the same of both primary endpoint and the pharmacodynamic timepoints. 3. From start of treatment (day 1) to the end of study visit 10 (day 14±2) 4. From start of chemotherapy (day 3) to evaluation visit (day 8) 5. From start of treatment (day 1) to visit 7 (day 7 ) or 9 (day 9) based on investigator's judgment. | — |
Countries
Bulgaria, Croatia, Czech Republic, Hungary, Italy, Russian Federation, Spain, United Kingdom
Contacts
Public ContactCorporate Clin Research Directorate
Menarini Ricerche S.p.A.
Outcome results
None listed