transfusion-dependent thalassemia or myelodysplastic syndrome at very low, low or intermediate (int-1) risk MedDRA version: 18.1 Level: LLT Classification code 10054658 Term: Thalassemia System Organ Class: 100000004850 MedDRA version: 18.1 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 100000004864
Conditions
Interventions
Product Code: ICL670
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients aged = 10 years 2. Patients with transfusion-dependent thalassemia and iron overload, requiring deferasirox DT at doses of = 30 mg/kg/day as per the investigator’s decision OR Patients with very low, low or intermediate (int-1) risk myelodysplastic syndrome (MDS) and iron overload, requiring deferasirox DT at doses of = 20 mg/kg/day as per the investigator’s decision. 3. History of transfusion of at least 20 PRBC units and anticipated to be transfused with at least 8 units of PRBCs annually during the study 4. Serum ferritin > 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria) Additional inclusion criteria as per full protocol may apply. Are the trial subjects under 18? yes 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 105 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Creatinine clearance below the contraindication limit in the locally approved prescribing information. Creatinine clearance will be estimated from serum creatinine at screening Visit 1 and screening Visit 2 and the mean value will be used for eligibility criteria. 2. Serum creatinine > 1.5 xULN at screening measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria). 3. ALT (SGPT) > 5xULN, unless LIC confirmed as >10 mg Fe/dw within 6 months prior to screening visit 1. 4. Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample at screening Visit 1 or screening Visit 2. 5. Patients with significant impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Additional exclusion criteria as per full protocol may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the overall safety of deferasirox FCT and deferasirox DT formulations in patients with transfusion-dependent thalassemia or myelodysplastic syndrome at low or intermediate (int-1) risk.;Secondary Objective: - To evaluate both formulations on selected GI AEs - To evaluate pharmacokinetics of both formulations - To evaluate both formulations on patient satisfaction and palatability using a Patient Reported Outcomes (PRO) questionnaire - To evaluate both formulations on patient’s GI symptoms using a PRO daily diary - To evaluate both formulations on patient compliance using pill count and a PRO daily diary;Primary end point(s): Overall safety, as measured by frequency and severity of adverse events and changes in laboratory values from baseline (serum creatinine, creatinine clearance, ALT, AST, platelets, RBC and WBC);Timepoint(s) of evaluation of this end point: Screening visit through post-treatment period - 30 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Frequency of selected GI AEs (diarrhea, constipation, nausea, vomiting, abdominal pain) 2) PK parameters 3) Domain scores of treatment satisfaction and palatability over time 4) Weekly average of daily scores of GI diary 5) Relative consumed FCT/DT counts 6) Patient-reported medication consumption;Timepoint(s) of evaluation of this end point: 1) on-treatment period (Day 1 - safety follow-up) - 28 weeks 2) week 1, 3, 13 and 21 • AUCtau, AUClast, Cmax, Tmax at week 1 and week 3 (only applies to PK subset A) • C2hr and Ctrough at week 3, 13 and 21 for all study patients 3) week 2, 3 and 13 and end of treatment (week 24 or within 7 days of last dose) 4) weekly (screening through end of treatment visit) - 26 weels 5) monthly 6) daily (Day 1/visit 3 - last visit) 24 weeks | — |
Countries
Argentina, Austria, France, Germany, Greece, Italy, Lebanon, Malaysia, Mexico, Russian Federation, Saudi Arabia, Spain, Thailand, United Arab Emirates, United Kingdom, United States
Contacts
Public ContactDrug Regulatory Affairs
Novartis Pharma GmbH
Outcome results
None listed