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Evaluating Use of Deferasirox as Compared to Deferoxamine in Treating Cardiac Iron Overload (CORDELIA)

Primary Purpose

Transfusional Iron Overload, Transfusional Hemosiderosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Core Study: Deferasirox
Core Study: Deferoxamine
Extension: deferoxamine to deferasirox
Extension: deferasirox to deferoxamine
Deferasirox
Deferoxamine
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transfusional Iron Overload focused on measuring iron overload, cardiac iron, haemosiderosis, myocardial T2*, left ventricular ejection fraction, LVEF, cardiac dysfunction, thalassaemia, Diamond Blackfan anemia, DBA, sideroblastic anemia, myelodysplastic syndromes, MDS (low and INT-1 risk as per the IPSS for MDS), liver MRI, deferasirox, deferoxamine, ICL670, DFO, cardiovascular magnetic resonance imaging

Eligibility Criteria

10 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Male or female patients, aged 10 years and above, with β-thalassemia major or DBA or sideroblastic anemia on chronic transfusion therapy, having given written consent to participate in the study.
  • Patients with cardiac iron as measured by a myocardial T2* value that is ≥ 6ms but not ≥ 20 ms.
  • Patients with a lifetime history of at least 50 units of red cell transfusions, and must be receiving at least ≥10 units/yr of red blood cells transfusions.
  • Patients with a left ventricular ejection fraction (LVEF) ≥ 56 % as determined by cardiovascular magnetic resonance (CMR).
  • Patients with liver iron content (LIC) value ≥ 3 mg Fe / g dw, as determined by liver MRI.

Exclusion criteria:

  • Patients with clinical symptoms of cardiac dysfunction.
  • Patients unable to undergo study assessments including MRI
  • Patients participating in another clinical trial or receiving an investigational drug.

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Experimental

Arm Label

Deferasirox

Deferasirox Placebo

Extension: deferoxamine to deferasirox

Extension: deferasirox to deferoxamine

Arm Description

20 mg/kg/day once daily (od) for 2 weeks, followed by 30 mg/kg/day od for 1 week and a subsequent continuation of 40 mg/kg/day

50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week

"DFO to ICL" (patients who switched from DFO to deferasirox in extension)

"ICL to DFO" (patients who switched from deferasirox to DFO in extension)

Outcomes

Primary Outcome Measures

Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment
Non- inferiority in efficacy of deferasirox compared to deferoxamine (DFO) in treating cardiac iron overload as measured by T2*. A non-inferiority margin of 0.9 (90%) was applied. Due to limitations in performing heart biopsies, T2* (T2 star), a Magnetic Resonance (MR) relaxation parameter expressed in milliseconds, as is an important tool to noninvasively quantify cardiac iron concentration. Studies have shown that myocardial T2* evaluations may predict cardiac events, e.g., impaired (<56%) left ventricular ejection fraction (LVEF) is prevalent among patients with low T2*: found in 62% of patients with T2*<8 ms; 20% with T2* of 8-12 ms; and in 5% with T2* >12 ms (Tanner 2006)

Secondary Outcome Measures

Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
An absolute change from baseline in LVEF after 12 months treatment with deferasirox and compared to.DFO was tested using an analysis of covariance model including baseline left ventricular ejection fraction (LVEF) as a covariate.
Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
An absolute change from baseline in LVEF after 6 months treatment with deferasirox and DFO was summarized
Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment
Summary statistics of T2* ratio Month 6/baseline
Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
An absolute change from baseline in LVESVI after 6 and 12 months treatment with deferasirox and DFO was summarized. Changes in cardiovascular magnetic resonance (CMR) measured left ventricular end systolic after 6 and 12 months treatment. Left ventricular (LV) end-systolic volume indexed to body surface area (ESVI) is a simple yet powerful echocardiographic marker of LV remodeling that can be measured easily. Left ventricular (LV) end-systolic volume (ESV) has been shown to be an important determinant of survival after myocardial infarction (MI)
Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
An absolute change from baseline in LVEDVI after 6, and 12 months treatment with deferasirox and DFO was summarized
Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI)
An absolute change from baseline in LVMI after 6, and 12 months treatment with deferasirox and DFO was summarized
Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine
The number of patients withdrawn from the study due to LVEF <50%, T2* <6 ms or significant decreases in T2* ≥ 33% from baseline was provided per treatment group.
Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period.
Number of patients with adverse events, serious adverse events and death
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau)
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, area under the plasma concentration-time curve for a dosing interval (AUCtau)
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax)
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, maximum plasma concentration (Cmax)
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. For trough concentration assessments, a 2-mL blood sample was to be taken on arrival at the study site, i.e. prior to the patient receiving the daily deferasirox dose (pre-dose blood sample). A second 2-mL blood sample was to be taken 2 hours later (post-dose sample). At all other visits (Visits 3 - 14), a pre-dose sample was to be taken. For PK profile assessments, 3 blood samples were taken after 1, 2, and 4 hours post-dose in addition to the 2-mL pre-dose
Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment
The measured T2* values, the ratio (post-baseline / baseline T2*) at Month 6, 12, 18 and 24 was summarized for FAS population along with two-sided 95% CIs. The geometric means of the ratio was presented for all treatment groups
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF)
Cardiac function endpoints (LVEF) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
Cardiac function endpoints (LVESVI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
Cardiac function endpoint (LVEDVI ) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI)
Cardiac function endpoints (LVMI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes
Extension Study: The Cardiac Iron Concentration From T2* Values
Cardiac iron concentration (derived from T2* values) at baseline, Months 6, 12, 18 and 24 were summarized by descriptive statistics. The absolute change from baseline at Months 6, 12, 18 and 24 were also summarized by treatment group. Lliver iron concentration is expressed in units (mg of iron / g of liver tissue dry weight (dw)
Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
Results of liver iron content (LIC) measurements by MRI was summarized by descriptive statistics. The absolute value and the absolute change from baseline in LIC at Months 6, 12, 18 and 24 were provided by treatment group.
Extension Study: Change in Serum Ferritin From Baseline by Month
Serum ferritin values was summarized by descriptive statistics. Absolute value and the absolute change from baseline in serum ferritin by month was provided by treatment group.
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax)
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, time to reach maximum plasma concentration (Tmax)

Full Information

First Posted
January 14, 2008
Last Updated
August 13, 2014
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00600938
Brief Title
Evaluating Use of Deferasirox as Compared to Deferoxamine in Treating Cardiac Iron Overload
Acronym
CORDELIA
Official Title
A Multicenter, Randomized, Open-label Phase II Trial Evaluating Deferasirox Compared With Deferoxamine in Patients With Cardiac Iron Overload Due to Chronic Blood Transfusions
Study Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a clinical research study in patients who have iron overload in the heart due to chronic blood transfusions. The study will have 2 treatment groups and will compare the safety and efficacy of chelation therapy with a medicine called deferasirox (ICL670) with another medicine called deferoxamine (DFO). The study is aimed at finding out which of the two medicines is the best for treating iron overload in the heart. Patients will be treated for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study treatment in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the heart and the liver will be evaluated using specific magnetic resonance imaging (MRI) assessments.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transfusional Iron Overload, Transfusional Hemosiderosis
Keywords
iron overload, cardiac iron, haemosiderosis, myocardial T2*, left ventricular ejection fraction, LVEF, cardiac dysfunction, thalassaemia, Diamond Blackfan anemia, DBA, sideroblastic anemia, myelodysplastic syndromes, MDS (low and INT-1 risk as per the IPSS for MDS), liver MRI, deferasirox, deferoxamine, ICL670, DFO, cardiovascular magnetic resonance imaging

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
197 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deferasirox
Arm Type
Experimental
Arm Description
20 mg/kg/day once daily (od) for 2 weeks, followed by 30 mg/kg/day od for 1 week and a subsequent continuation of 40 mg/kg/day
Arm Title
Deferasirox Placebo
Arm Type
Active Comparator
Arm Description
50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week
Arm Title
Extension: deferoxamine to deferasirox
Arm Type
Experimental
Arm Description
"DFO to ICL" (patients who switched from DFO to deferasirox in extension)
Arm Title
Extension: deferasirox to deferoxamine
Arm Type
Experimental
Arm Description
"ICL to DFO" (patients who switched from deferasirox to DFO in extension)
Intervention Type
Drug
Intervention Name(s)
Core Study: Deferasirox
Other Intervention Name(s)
"ICL to ICL"
Intervention Description
20 mg/kg/day once daily (od) for 2 weeks, followed by 30 mg/kg/day od for 1 week and a subsequent continuation of 40 mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Core Study: Deferoxamine
Other Intervention Name(s)
"DFO to DFO"
Intervention Description
50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week
Intervention Type
Drug
Intervention Name(s)
Extension: deferoxamine to deferasirox
Other Intervention Name(s)
"DFO to ICL"
Intervention Description
40 mg/kg deferasirox once daily administered 30 minutes before taking food.
Intervention Type
Drug
Intervention Name(s)
Extension: deferasirox to deferoxamine
Other Intervention Name(s)
"ICL to DFO"
Intervention Description
DFO at a target range of 50 mg/kg/day to 60 mg/kg/day via subcutaneous (sc) infusion lasting a period of 8 to 12 hrs administered for 5 to 7 days per week,
Intervention Type
Drug
Intervention Name(s)
Deferasirox
Intervention Type
Drug
Intervention Name(s)
Deferoxamine
Primary Outcome Measure Information:
Title
Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment
Description
Non- inferiority in efficacy of deferasirox compared to deferoxamine (DFO) in treating cardiac iron overload as measured by T2*. A non-inferiority margin of 0.9 (90%) was applied. Due to limitations in performing heart biopsies, T2* (T2 star), a Magnetic Resonance (MR) relaxation parameter expressed in milliseconds, as is an important tool to noninvasively quantify cardiac iron concentration. Studies have shown that myocardial T2* evaluations may predict cardiac events, e.g., impaired (<56%) left ventricular ejection fraction (LVEF) is prevalent among patients with low T2*: found in 62% of patients with T2*<8 ms; 20% with T2* of 8-12 ms; and in 5% with T2* >12 ms (Tanner 2006)
Time Frame
12 Month
Secondary Outcome Measure Information:
Title
Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
Description
An absolute change from baseline in LVEF after 12 months treatment with deferasirox and compared to.DFO was tested using an analysis of covariance model including baseline left ventricular ejection fraction (LVEF) as a covariate.
Time Frame
12 Month
Title
Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
Description
An absolute change from baseline in LVEF after 6 months treatment with deferasirox and DFO was summarized
Time Frame
6 Month
Title
Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment
Description
Summary statistics of T2* ratio Month 6/baseline
Time Frame
6 Month
Title
Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
Description
An absolute change from baseline in LVESVI after 6 and 12 months treatment with deferasirox and DFO was summarized. Changes in cardiovascular magnetic resonance (CMR) measured left ventricular end systolic after 6 and 12 months treatment. Left ventricular (LV) end-systolic volume indexed to body surface area (ESVI) is a simple yet powerful echocardiographic marker of LV remodeling that can be measured easily. Left ventricular (LV) end-systolic volume (ESV) has been shown to be an important determinant of survival after myocardial infarction (MI)
Time Frame
6 Month, 12 Month
Title
Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
Description
An absolute change from baseline in LVEDVI after 6, and 12 months treatment with deferasirox and DFO was summarized
Time Frame
6 Month, 12 Month
Title
Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI)
Description
An absolute change from baseline in LVMI after 6, and 12 months treatment with deferasirox and DFO was summarized
Time Frame
6 Month, 12 Month
Title
Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine
Description
The number of patients withdrawn from the study due to LVEF <50%, T2* <6 ms or significant decreases in T2* ≥ 33% from baseline was provided per treatment group.
Time Frame
12 Month
Title
Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period.
Description
Number of patients with adverse events, serious adverse events and death
Time Frame
12 Month
Title
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau)
Description
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, area under the plasma concentration-time curve for a dosing interval (AUCtau)
Time Frame
12 Month
Title
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax)
Description
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, maximum plasma concentration (Cmax)
Time Frame
12 Month
Title
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data
Description
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. For trough concentration assessments, a 2-mL blood sample was to be taken on arrival at the study site, i.e. prior to the patient receiving the daily deferasirox dose (pre-dose blood sample). A second 2-mL blood sample was to be taken 2 hours later (post-dose sample). At all other visits (Visits 3 - 14), a pre-dose sample was to be taken. For PK profile assessments, 3 blood samples were taken after 1, 2, and 4 hours post-dose in addition to the 2-mL pre-dose
Time Frame
Month 1 and month 2 (pre-dose, 1,2 and 4 hours post-dose)
Title
Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment
Description
The measured T2* values, the ratio (post-baseline / baseline T2*) at Month 6, 12, 18 and 24 was summarized for FAS population along with two-sided 95% CIs. The geometric means of the ratio was presented for all treatment groups
Time Frame
Months 6, 12, 18 and 24
Title
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF)
Description
Cardiac function endpoints (LVEF) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Time Frame
Months 6, 12, 18 and 24
Title
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
Description
Cardiac function endpoints (LVESVI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Time Frame
Months 6, 12, 18 and 24
Title
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
Description
Cardiac function endpoint (LVEDVI ) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Time Frame
Months 6, 12, 18 and 24
Title
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI)
Description
Cardiac function endpoints (LVMI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes
Time Frame
Months 6, 12, 18 and 24
Title
Extension Study: The Cardiac Iron Concentration From T2* Values
Description
Cardiac iron concentration (derived from T2* values) at baseline, Months 6, 12, 18 and 24 were summarized by descriptive statistics. The absolute change from baseline at Months 6, 12, 18 and 24 were also summarized by treatment group. Lliver iron concentration is expressed in units (mg of iron / g of liver tissue dry weight (dw)
Time Frame
Months 6, 12, 18 and 24
Title
Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
Description
Results of liver iron content (LIC) measurements by MRI was summarized by descriptive statistics. The absolute value and the absolute change from baseline in LIC at Months 6, 12, 18 and 24 were provided by treatment group.
Time Frame
Months 6, 12, 18 and 24
Title
Extension Study: Change in Serum Ferritin From Baseline by Month
Description
Serum ferritin values was summarized by descriptive statistics. Absolute value and the absolute change from baseline in serum ferritin by month was provided by treatment group.
Time Frame
Months 6, 12, 18 and 24
Title
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax)
Description
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, time to reach maximum plasma concentration (Tmax)
Time Frame
12 Month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Male or female patients, aged 10 years and above, with β-thalassemia major or DBA or sideroblastic anemia on chronic transfusion therapy, having given written consent to participate in the study. Patients with cardiac iron as measured by a myocardial T2* value that is ≥ 6ms but not ≥ 20 ms. Patients with a lifetime history of at least 50 units of red cell transfusions, and must be receiving at least ≥10 units/yr of red blood cells transfusions. Patients with a left ventricular ejection fraction (LVEF) ≥ 56 % as determined by cardiovascular magnetic resonance (CMR). Patients with liver iron content (LIC) value ≥ 3 mg Fe / g dw, as determined by liver MRI. Exclusion criteria: Patients with clinical symptoms of cardiac dysfunction. Patients unable to undergo study assessments including MRI Patients participating in another clinical trial or receiving an investigational drug. Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Novartis Investigative Site
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530021
Country
China
Facility Name
Novartis Investigative Site
City
Limassol
ZIP/Postal Code
3304
Country
Cyprus
Facility Name
Novartis Investigative Site
City
Cairo
Country
Egypt
Facility Name
Novartis Investigative Site
City
Mansoura
Country
Egypt
Facility Name
Novartis Investigative Site
City
Cagliari
State/Province
CA
ZIP/Postal Code
09121
Country
Italy
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16128
Country
Italy
Facility Name
Novartis Investigative Site
City
Hazmiyeh
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Novartis Investigative Site
City
Antalya
ZIP/Postal Code
07070
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
Facility Name
Novartis Investigative Site
City
Dubai
ZIP/Postal Code
9115
Country
United Arab Emirates
Facility Name
Novartis Investigative Site
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
N19 5NF
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
NW1 2PJ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25345697
Citation
Pennell DJ, Porter JB, Piga A, Lai YR, El-Beshlawy A, Elalfy M, Yesilipek A, Kilinc Y, Habr D, Musallam KM, Shen J, Aydinok Y; CORDELIA study investigators. Sustained improvements in myocardial T2* over 2 years in severely iron-overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine. Am J Hematol. 2015 Feb;90(2):91-6. doi: 10.1002/ajh.23876. Epub 2014 Nov 19.
Results Reference
derived
PubMed Identifier
24385534
Citation
Pennell DJ, Porter JB, Piga A, Lai Y, El-Beshlawy A, Belhoul KM, Elalfy M, Yesilipek A, Kilinc Y, Lawniczek T, Habr D, Weisskopf M, Zhang Y, Aydinok Y; CORDELIA study investigators. A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in beta-thalassemia major (CORDELIA). Blood. 2014 Mar 6;123(10):1447-54. doi: 10.1182/blood-2013-04-497842. Epub 2014 Jan 2.
Results Reference
derived

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Evaluating Use of Deferasirox as Compared to Deferoxamine in Treating Cardiac Iron Overload

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