Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)

Novartis

Status and phase: Completed; Phase 2

Conditions: Chronic Iron Overload Due to Transfusion-dependant Anemias

Treatments: Drug: Defearisox film-coated tablet; Drug: Deferasirox dispersible tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT02125877

CICL670F2201

Details and patient eligibility

About

Assessed the new film-coated tablet formulation to the currently approved dispersible tablet formulation with regards to overall safety, Gastrointestinal (GI) tolerability, palatability, satisfaction and compliance

Enrollment: 173 patients

Sex: All

Ages: 10+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Male and female patients aged ≥ 10 years
• 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) risk myelodysplastic syndrome (MDS) and iron overload, requiring deferasirox DT at doses of ≥ 20 mg/kg/day as per the investigator's decision.
• 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
• Serum ferritin > 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).

Key Exclusion Criteria:

• 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.
• 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).
• ALT (SGPT) > 5xULN, unless LIC confirmed as >10 mg Fe/dw within 6 months prior to screening visit 1.
• 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.
• 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).
• Liver disease with severity of Child-Pugh Class B or C

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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173 participants in 2 patient groups

Deferasirox dispersible tablet (DFX-DT)

Active Comparator group

Description:

Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.

Treatment:

Drug: Deferasirox dispersible tablet

Deferasirox film-coated tablet (DFX-FCT)

Experimental group

Description:

Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose

Treatment:

Drug: Defearisox film-coated tablet