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

Phase 1

Active, not recruiting

• Conditions: transfusion-dependent thalassemia or myelodysplastic syndrome at very low, low or intermediate (int-1) risk; MedDRA version: 18.1Level: LLTClassification code 10054658Term: ThalassemiaSystem Organ Class: 100000004850; MedDRA version: 18.1Level: LLTClassification code 10028534Term: Myelodysplastic syndrome NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-004167-32-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06-20
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 150

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 perfull 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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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<br>- To evaluate pharmacokinetics of both formulations<br>- To evaluate both formulations on patient satisfaction and palatability using a Patient Reported Outcomes (PRO) questionnaire<br>- To evaluate both formulations on patient’s GI symptoms using a PRO daily diary<br>- 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 Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Frequency of selected GI AEs (diarrhea, constipation, nausea, vomiting, abdominal pain)<br>2) PK parameters<br>3) Domain scores of treatment satisfaction and palatability over time<br>4) Weekly average of daily scores of GI diary<br>5) Relative consumed FCT/DT counts<br>6) Patient-reported medication consumption;Timepoint(s) of evaluation of this end point: 1) on-treatment period (Day 1 - safety follow-up) - 28 weeks<br>2) week 1, 3, 13 and 21<br>• AUCtau, AUClast, Cmax, Tmax at week 1 and week 3 (only applies to PK subset A)<br> • C2hr and Ctrough at week 3, 13 and 21 for all study patients<br>3) week 2, 3 and 13 and end of treatment (week 24 or within 7 days of last dose)<br>4) weekly (screening through end of treatment visit) - 26 weeks<br>5) monthly<br>6) daily (Day 1/visit 3 - last visit) 24 weeks