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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00600938

Collaborator

(none)

197

Enrollment

Locations

Arms

Duration (Months)

9.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Transfusional Iron Overload Transfusional Hemosiderosis	Drug: Core Study: Deferasirox Drug: Core Study: Deferoxamine Drug: Extension: deferoxamine to deferasirox Drug: Extension: deferasirox to deferoxamine Drug: Deferasirox Drug: Deferoxamine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

197 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferasirox 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	Drug: Core Study: Deferasirox 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 Other Names: "ICL to ICL" Drug: Deferasirox
Active Comparator: Deferasirox Placebo 50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week	Drug: Core Study: Deferoxamine 50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week Other Names: "DFO to DFO" Drug: Deferoxamine
Experimental: Extension: deferoxamine to deferasirox "DFO to ICL" (patients who switched from DFO to deferasirox in extension)	Drug: Extension: deferoxamine to deferasirox 40 mg/kg deferasirox once daily administered 30 minutes before taking food. Other Names: "DFO to ICL"
Experimental: Extension: deferasirox to deferoxamine "ICL to DFO" (patients who switched from deferasirox to DFO in extension)	Drug: Extension: deferasirox to deferoxamine 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, Other Names: "ICL to DFO"

Outcome Measures

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 [12 Month]
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) [12 Month]
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) [6 Month]
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 [6 Month]
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) [6 Month, 12 Month]
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) [6 Month, 12 Month]
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) [6 Month, 12 Month]
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 [12 Month]
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. [12 Month]
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) [12 Month]
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) [12 Month]
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 [Month 1 and month 2 (pre-dose, 1,2 and 4 hours post-dose)]
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 [Months 6, 12, 18 and 24]
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) [Months 6, 12, 18 and 24]
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) [Months 6, 12, 18 and 24]
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) [Months 6, 12, 18 and 24]
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) [Months 6, 12, 18 and 24]
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 [Months 6, 12, 18 and 24]
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 [Months 6, 12, 18 and 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 [Months 6, 12, 18 and 24]
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) [12 Month]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 1X8
2	Novartis Investigative Site	Nanning	Guangxi	China	530021
3	Novartis Investigative Site	Limassol		Cyprus	3304
4	Novartis Investigative Site	Cairo		Egypt
5	Novartis Investigative Site	Mansoura		Egypt
6	Novartis Investigative Site	Cagliari	CA	Italy	09121
7	Novartis Investigative Site	Genova	GE	Italy	16128
8	Novartis Investigative Site	Hazmiyeh		Lebanon
9	Novartis Investigative Site	Taipei		Taiwan	10002
10	Novartis Investigative Site	Bangkok		Thailand	10330
11	Novartis Investigative Site	Bangkok		Thailand	10700
12	Novartis Investigative Site	Adana		Turkey	01330
13	Novartis Investigative Site	Ankara		Turkey	06100
14	Novartis Investigative Site	Antalya		Turkey	07070
15	Novartis Investigative Site	Istanbul		Turkey	34093
16	Novartis Investigative Site	Izmir		Turkey	35040
17	Novartis Investigative Site	Dubai		United Arab Emirates	9115
18	Novartis Investigative Site	Leeds	West Yorkshire	United Kingdom	LS9 7TF
19	Novartis Investigative Site	Leeds		United Kingdom	LS9 7TF
20	Novartis Investigative Site	London		United Kingdom	N19 5NF
21	Novartis Investigative Site	London		United Kingdom	NW1 2PJ

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT00600938

Other Study ID Numbers:

CICL670A2206
2007-000766-20

First Posted:

Jan 25, 2008

Last Update Posted:

Aug 27, 2014

Last Verified:

Aug 1, 2014

Keywords provided by Novartis Pharmaceuticals

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)

cardiovascular magnetic resonance imaging

Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Patients randomized to 1 of 2 treatment grps ICL or DFO, 20 mg/kg/day once daily for 2 wks, followed by 30 mg/kg/day od for 1 wk and 40 mg/kg/day od (DFO) target dose of 50 to 60 mg/kg/day 8 to 12 hour for 5 to 7 days/wk. In ext. pts could either stay in the same grp from core or could switch grps: ICL to ICL, DFO to DFO, DFO to ICL and ICL to DFO

Arm/Group Title	Deferasirox (ICL). For Extension Labeled as ICL to ICL	Deferoxamine (DFO). For Extension Labeled as DFO to DFO	DFO to ICL (Deferoxamine to Deferasirox)	ICL to DFO (Deferasirox to Deferoxamine)
Arm/Group 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)
Period Title: Core Study
STARTED	98	99	0	0
Core Safety Set	96	91	0	0
Per Protocol Set (PPS)	91	81	0	0
COMPLETED	82	78	0	0
NOT COMPLETED	16	21	0	0
Period Title: Core Study
STARTED	74	29	42	1
Extension Safety Set	73	29	42	1
COMPLETED	65	24	33	0
NOT COMPLETED	9	5	9	1

Baseline Characteristics

Arm/Group Title	Core: Deferasirox (ICL)	Core: Deferoxamine (DFO)	Total
Arm/Group 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	Total of all reporting groups
Overall Participants	98	99	197
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	19.9 (6.53)	19.7 (6.32)	19.8 (6.41)
Sex: Female, Male (Count of Participants)
Female	40 40.8%	42 42.4%	82 41.6%
Male	58 59.2%	57 57.6%	115 58.4%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations.

Arm/Group Title	Core: Deferasirox (ICL)	Core: Deferoxamine (DFO)
Arm/Group 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 for 12 months.	50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week for 12 months.
Measure Participants	91	81
Geometric Mean (95% Confidence Interval) [Millisecond]	1.12 (3.687)	1.07 (2.931)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations.

Arm/Group Title	Core: Deferasirox (ICL). For Extension Labeled as ICL to ICL	Core: Deferoxamine (DFO). For Extension Labeled as DFO to DFO
Arm/Group 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 for 12 month	50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week for 12 month
Measure Participants	91	81
Least Squares Mean (Standard Error) [Percent]	-0.5 (0.47)	-0.0 (0.49)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations

Arm/Group Title	Core: Deferasirox (ICL). For Extension Labeled as ICL to ICL	Deferoxamine (DFO). For Extension Labeled as DFO to DFO
Arm/Group 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 for 12 month	50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week
Measure Participants	85	73
Mean (Standard Deviation) [Percent]	-0.95 (4.485)	-0.37 (4.389)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations

Arm/Group Title	Core: Deferasirox (ICL). For Extension Labeled as ICL to ICL	Core: Deferoxamine (DFO). For Extension Labeled as DFO to DFO
Arm/Group 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 for 12 month	50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week for 12 month
Measure Participants	85	73
Geometric Mean (95% Confidence Interval) [Ratio]	1.04 (4.752)	1.04 (4.417)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations

Arm/Group Title	Core: Deferasirox (ICL). For Extension Labeled as ICL to ICL	Core: Deferoxamine (DFO). For Extension Labeled as DFO to DFO
Arm/Group 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 for 12 month	50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week for 12 month
Measure Participants	91	81
Change from baseline at 6 Month (n= 85, 73)	1.8 (8.021)	0.88 (8.919)
Change from Baseline at 12 Month/EOS (n= 91, 81)	1.57 (8.040)	0.10 (10.387)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations

Arm/Group Title	Core; Deferasirox (ICL). For Extension Labeled as ICL to ICL	Core: Deferoxamine (DFO). For Extension Labeled as DFO to DFO
Arm/Group 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 for 12 month	50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week
Measure Participants	91	81
Change from Baseline at 6 Month (n= 85, 73)	1.81 (14.515)	1.48 (19.188)
Change from Baseline at 12 Month/EOS (n= 91, 81)	1.79 (13.122)	1.10 (20.485)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations

Arm/Group Title	Core: Deferasirox (ICL). For Extension Labeled as ICL to ICL	Core: Deferoxamine (DFO). For Extension Labeled as DFO to DFO
Arm/Group 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 for 12 month	50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week for 12 month
Measure Participants	91	81
Change from Baseline at 6 Month (n= 85, 73)	1.01 (13.102)	3.32 (13.585)
Change from Baseline at 12 Month/EOS (n= 91, 81)	4.13 (15.055)	5.25 (14.973)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations

Arm/Group Title	Core: Deferasirox (ICL). For Extension Labeled as ICL to ICL	Core; Deferoxamine (DFO). For Extension Labeled as DFO to DFO
Arm/Group 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 for 12 month	50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week for 12 month
Measure Participants	98	99
Number [Participants]	3 3.1%	2 2%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Safety Set (SS) consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received. Treatment received is defined as first study drug administered

Arm/Group Title	Core: Deferasirox (ICL). For Extension Labeled as ICL to ICL	Core: Deferoxamine (DFO). For Extension Labeled as DFO to DFO
Arm/Group 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 for 12 month
Measure Participants	96	91
At least one AE	65 66.3%	69 69.7%
Serious Adverse Events	10 10.2%	10 10.1%
Death. None were considered related to study drug.	1 1%	1 1%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Analysis Set (PAS): PAS 2: All randomized patients who received the same dose of deferasirox for at least four consecutive days prior to PK sample collection and completed PK sample collection specified in the protocol at Visit 3 or Visit 4 (pre-dose, 1, 2, and 4 hours post-dose).

Arm/Group Title	Deferasirox (ICL). For Extension Labeled as ICL to ICL
Arm/Group 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
Measure Participants	13
Mean (Standard Deviation) [(h.ng/mL)]	2129.70 (930.202)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Analysis Set (PAS): PAS 2: All randomized patients who received the same dose of deferasirox for at least four consecutive days prior to PK sample collection and completed PK sample collection specified in the protocol at Visit 3 or Visit 4 (pre-dose, 1, 2, and 4 hours post-dose).

Arm/Group Title	Deferasirox (ICL). For Extension Labeled as ICL to ICL
Arm/Group 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
Measure Participants	13
Mean (Standard Deviation) [umol/L]	150.09 (59.143)

12. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Analysis Set (PAS): PAS 2: All randomized patients who received the same dose of deferasirox for at least four consecutive days prior to PK sample collection and completed PK sample collection specified in the protocol at Visit 3 or Visit 4 (pre-dose, 1, 2, and 4 hours post-dose).

Arm/Group Title	Deferasirox (ICL). For Extension Labeled as ICL to ICL
Arm/Group 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
Measure Participants	13
Month 1, 0 hour (predose)	32.25 (21.288)
Month 1, 1 hour (post dos)	96.32 (35.799)
Month 1, 2 hour (post dose)	136.47 (51.831)
Month 1, 4 hour (post dose)	133.33 (62.815)
Month 2, 0 hour (predose)	38.66 (29.887)
Month 2, 1 hour (post dose)	119.48 (38.709)
Month 2, 2 hour (post dose)	177.19 (55.343)
Month 2, 4 hour (post dose)	180.76 (57.877)

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase.

Arm/Group Title	Extension : ICL to ICL	Extension: DFO to DFO	Extension; DFO to ICL	Extension: ICL to DFO
Arm/Group Description	Patients from core continued and received same dose 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	Patients from core continued and received same 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)
Measure Participants	74	29	42	1
Month 6 (n=71,26,40,1)	1.06 (2.763)	1.05 (2.024)	1.03 (2.778)	1.00 (0)
Month 12(n=66, 29, 41, 1)	1.17 (3.654)	1.06 (2.680)	1.07 (3.411)	1.17 (0)
Month 18 (n=68, 26, 39, 1)	1.24 (5.112)	1.18 (3.748)	1.13 (4.376)	1.05 (0)
Month 24 (n=63, 25, 33, 1)	1.38 (5.277)	1.33 (5.821)	1.21 (4.658)	1.11 (0)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase. Cardiac function parameters over time - excluding patients in Egypt sites.

Arm/Group Title	Extension: ICL to ICL	Extension: DFO to DFO	Extension: DFO to ICL	Extension: ICL to DFO
Arm/Group Description	Patients from core continued and received same dose 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	Patients from core continued and received same 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)
Measure Participants	74	29	42	1
Month 6 (n=71,26,40,1)	-1.1 (4.96)	-1.8 (3.59)	0.1 (4.60)	-1.0 (0)
Month 12 (n= 66,29,42,1)	-0.5 (5.02)	0.3 (5.13)	0.0 (3.73)	0 (0)
Month 18 (n=68,26,39,1 )	-0.1 (4.84)	-0.8 (5.14)	-1.3 (3.74)	-10.0 (0)
Month 24 (n= 63,25,33,1)	0.6 (4.72)	-0.6 (5.02)	0.2 (4.82)	-18.0 (0)

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase. Cardiac function parameters over time - excluding patients in Egypt sites.

Arm/Group Title	Extension: ICL to ICL	Extension: DFO to DFO	Extension: DFO to ICL	Extension: ICL to DFO
Arm/Group Description	Patients from core continued and received same 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	Patients from core continued and received same 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)
Measure Participants	74	29	42	1
Month 6 (n=69,26,40,1)	1.7 (7.98)	3.4 (10.40)	0 (8.22)	1 (0)
Month 12 (n=64,28,40,1 )	1.5 (7.42)	-0.8 (9.74)	0.6 (9.69)	2 (0)
Month 18 (n=67,24,35,1 )	2.4 (10.58)	2.8 (11.54)	4.1 (6.88)	28.0 (0)
Month 24 (n=60,23,33,0 )	1.6 (10.21)	4.3 (8.66)	1.7 (8.56)	NA (NA)

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase. Cardiac function parameters over time - excluding patients in Egypt sites

Arm/Group Title	Extension: ICL to ICL	Extension: DFO to DFO	Extension: DFO to ICL	Extension: ICL to DFO
Arm/Group Description	Patients from core continued and received same 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	Patients from core continued and received same 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)
Measure Participants	74	29	42	1
Month 6 (n=69,26,40,1)	2.0 (14.19)	3.5 (21.95)	0.5 (18.77)	1.0 (0)
Month 12 (n=64,28,40,1)	2.0 (13.49)	-0.6 (18.56)	3.0 (23.06)	4.0 (0)
Month 18 (n=67,24,35,1)	6.5 (17.80)	4.2 (19.75)	8.3 (16.08)	36.0 (0)
Month 24 (n=60,23,33,0)	3.4 (21.15)	9.5 (14.60)	5.4 (13.97)	NA (NA)

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase. Cardiac function parameters over time - excluding patients in Egypt sites

Arm/Group Title	Extension: ICL to ICL	Extension: DFO to DFO	Extension: DFO to ICL	Extension: ICL to DFO
Arm/Group Description	Patients from core continued and received same 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	Patients from core continued and received same 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)
Measure Participants	74	29	42	1
Month 6 (n=69,26,40,1)	1.4 (12.37)	1.8 (15.98)	3.2 (13.38)	-6.0 (0)
Month 12 (n=64,28,40,1)	4.2 (13.90)	9.1 (14.19)	3.4 (16.54)	1 (0)
Month 18 (n=67,24,35,1)	4.8 (14.37)	-0.1 (16.87)	4.0 (14.39)	37.0 (0)
Month 24 (n=60,23,33,0)	5.6 (13.00)	6.7 (14.96)	10.3 (13.32)	NA (NA)

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase

Arm/Group Title	Extension: ICL to ICL	Extension: DFO to DFO	Extension: DFO to ICL	Extension: ICL to DFO
Arm/Group Description	Patients from core continued and received same 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	Patients from core continued and received same 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)
Measure Participants	74	26	40	1
Month 6 (n=71,26,40,1)	-0.12 (0.587)	-0.12 (0.539)	-0.08 (0.465)	0 (0)
Month 12 (n=66,29,41,1)	-0.38 (0.674)	-0.12 (0.695)	-0.14 (0.490)	-0.77 (0)
Month 18 (n=68,26,39,1)	-0.47 (0.789)	-0.45 (0.797)	-0.20 (0.607)	-0.24 (0)
Month 24 (n=63,25,33,1)	-0.70 (0.834)	-0.69 (0.989)	-0.34 (0.863)	-0.52 (0)

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase

Arm/Group Title	Extension: ICL to ICL	Extension: DFO to DFO	Extension: DFO to ICL	Extension: ICL to DFO
Arm/Group Description	Patients from core continued and received same 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	Patients from core continued and received same 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)
Measure Participants	74	29	42	1
Month 6 (n=71,26,38,1)	-4.56 (7.467)	-12.66 (7.821)	-6.30 (7.375)	-3.80 (0)
Month 12 (n=69,29,40,1)	-10.22 (10.674)	-19.44 (11.446)	-7.98 (9.310)	-3.90 (0)
Month 18 (n=70,23,38,1)	-12.26 (13.938)	-26.09 (13.443)	-10.87 (11.116)	-2.90 (0)
Month 24 (n=60,24,33,1)	-15.74 (15.205)	-26.02 (14.867)	-10.96 (11.070)	-3.20 (0)

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase

Arm/Group Title	Extension: ICL to ICL	Extension: DFO to DFO	Extension: DFO to ICL	Extension: ICL to DFO
Arm/Group Description	Patients from core continued and received same 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	Patients from core continued and received same 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)
Measure Participants	74	29	42	1
Month 6 (n=72,28,38,0)	-626.10 (1541.406)	-1307.14 (1520.877)	-1054.87 (1967.651)	NA (NA)
Month 12 (n=70,29,40,1)	-988.46 (2883.416)	-1877.00 (1877.745)	-1223.73 (1808.056)	-498.00 (0)
Month 18 (n=66,24,39,1)	-1962.14 (2225.438)	-2426.92 (2685.817)	-1494.82 (1511.257)	-1067.00 (0)
Month 24 (n=59,24,30,0)	-2239.03 (2178.564)	-2724.00 (2693.583)	-1513.23 (2278.144)	NA (NA)

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Analysis Set (PAS): PAS 2: All randomized patients who received the same dose of deferasirox for at least four consecutive days prior to PK sample collection and completed PK sample collection specified in the protocol at Visit 3 or Visit 4 (pre-dose, 1, 2, and 4 hours post-dose).

Arm/Group Title	Deferasirox (ICL). For Extension Labeled as ICL to ICL
Arm/Group 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
Measure Participants	13
Median (Inter-Quartile Range) [(h)]	4.00 (930.202)

Adverse Events

	Core Phase - ICL670		Core Phase - DFO		Extension Phase - ICL to ICL		Extension Phase - DFO to DFO		Extension Phase - DFO to ICL		Extension Phase - ICL to DFO
Time Frame
Adverse Event Reporting Description	Core : The safety set consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline. safety assessment. Extension: one patient assigned to the deferasirox arm died before receiving treatment in the extension phase

Arm/Group Title	Core Phase - ICL670		Core Phase - DFO		Extension Phase - ICL to ICL		Extension Phase - DFO to DFO		Extension Phase - DFO to ICL		Extension Phase - ICL to DFO
Arm/Group Description	Patients from core continued and received same 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		Patients from core continued and received same 50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week		Patients from core continued and received same 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		Patients from core continued and received same 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)
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Core Phase - ICL670		Core Phase - DFO		Extension Phase - ICL to ICL		Extension Phase - DFO to DFO		Extension Phase - DFO to ICL		Extension Phase - ICL to DFO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/96 (10.4%)		10/91 (11%)		14/73 (19.2%)		4/29 (13.8%)		9/42 (21.4%)		0/1 (0%)
Blood and lymphatic system disorders
Hypersplenism	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Neutropenia	0/96 (0%)		0/91 (0%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Cardiac disorders
Arrhythmia	1/96 (1%)		0/91 (0%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Endocrine disorders
Hypogonadism	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/96 (1%)		1/91 (1.1%)		1/73 (1.4%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Colitis	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Diarrhoea	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Duodenal ulcer haemorrhage	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Dyspepsia	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Gastric haemorrhage	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Gastritis	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Ileus	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Oesophageal rupture	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Vomiting	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
General disorders
Face oedema	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Local swelling	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Pyrexia	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		1/29 (3.4%)		0/42 (0%)		0/1 (0%)
Hepatobiliary disorders
Cholecystitis	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Cholelithiasis	1/96 (1%)		1/91 (1.1%)		1/73 (1.4%)		1/29 (3.4%)		0/42 (0%)		0/1 (0%)
Infections and infestations
Abdominal abscess	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Acute tonsillitis	1/96 (1%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Amoebiasis	1/96 (1%)		0/91 (0%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Anal abscess	0/96 (0%)		0/91 (0%)		0/73 (0%)		1/29 (3.4%)		0/42 (0%)		0/1 (0%)
Appendicitis	0/96 (0%)		1/91 (1.1%)		1/73 (1.4%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Bronchitis	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Bronchopneumonia	0/96 (0%)		0/91 (0%)		0/73 (0%)		1/29 (3.4%)		0/42 (0%)		0/1 (0%)
Gastroenteritis	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Gastrointestinal infection	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Herpes zoster	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Influenza	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Liver abscess	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Meningitis	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Pneumonia	0/96 (0%)		0/91 (0%)		0/73 (0%)		1/29 (3.4%)		0/42 (0%)		0/1 (0%)
Tooth infection	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Urinary tract infection	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Wound infection	0/96 (0%)		0/91 (0%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Yersinia infection	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Injury, poisoning and procedural complications
Radius fracture	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Calcium deficiency	0/96 (0%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Haemosiderosis	0/96 (0%)		1/91 (1.1%)		2/73 (2.7%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Hyperglycaemia	1/96 (1%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Hypocalcaemia	0/96 (0%)		0/91 (0%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Iron overload	0/96 (0%)		2/91 (2.2%)		2/73 (2.7%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Pain in jaw	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Nervous system disorders
Grand mal convulsion	0/96 (0%)		1/91 (1.1%)		0/73 (0%)		0/29 (0%)		0/42 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/96 (0%)		0/91 (0%)		0/73 (0%)		1/29 (3.4%)		0/42 (0%)		0/1 (0%)
Wheezing	0/96 (0%)		0/91 (0%)		0/73 (0%)		1/29 (3.4%)		0/42 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Core Phase - ICL670		Core Phase - DFO		Extension Phase - ICL to ICL		Extension Phase - DFO to DFO		Extension Phase - DFO to ICL		Extension Phase - ICL to DFO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/96 (62.5%)		58/91 (63.7%)		56/73 (76.7%)		19/29 (65.5%)		36/42 (85.7%)		1/1 (100%)
Blood and lymphatic system disorders
Thrombocytosis	0/96 (0%)		4/91 (4.4%)		1/73 (1.4%)		2/29 (6.9%)		2/42 (4.8%)		0/1 (0%)
Endocrine disorders
Hypogonadism	2/96 (2.1%)		2/91 (2.2%)		0/73 (0%)		0/29 (0%)		2/42 (4.8%)		1/1 (100%)
Eye disorders
Conjunctivitis	1/96 (1%)		2/91 (2.2%)		4/73 (5.5%)		0/29 (0%)		3/42 (7.1%)		0/1 (0%)
Gastrointestinal disorders
Abdominal pain	7/96 (7.3%)		2/91 (2.2%)		7/73 (9.6%)		1/29 (3.4%)		3/42 (7.1%)		0/1 (0%)
Abdominal pain upper	5/96 (5.2%)		5/91 (5.5%)		6/73 (8.2%)		3/29 (10.3%)		5/42 (11.9%)		0/1 (0%)
Diarrhoea	12/96 (12.5%)		4/91 (4.4%)		10/73 (13.7%)		0/29 (0%)		9/42 (21.4%)		1/1 (100%)
Nausea	6/96 (6.3%)		2/91 (2.2%)		4/73 (5.5%)		1/29 (3.4%)		4/42 (9.5%)		0/1 (0%)
Vomiting	6/96 (6.3%)		1/91 (1.1%)		6/73 (8.2%)		0/29 (0%)		4/42 (9.5%)		0/1 (0%)
General disorders
Fatigue	1/96 (1%)		2/91 (2.2%)		0/73 (0%)		0/29 (0%)		3/42 (7.1%)		0/1 (0%)
Injection site reaction	0/96 (0%)		3/91 (3.3%)		0/73 (0%)		0/29 (0%)		3/42 (7.1%)		0/1 (0%)
Pyrexia	5/96 (5.2%)		5/91 (5.5%)		6/73 (8.2%)		3/29 (10.3%)		5/42 (11.9%)		1/1 (100%)
Infections and infestations
Acute tonsillitis	1/96 (1%)		3/91 (3.3%)		1/73 (1.4%)		1/29 (3.4%)		3/42 (7.1%)		0/1 (0%)
Bronchitis	1/96 (1%)		3/91 (3.3%)		1/73 (1.4%)		0/29 (0%)		3/42 (7.1%)		0/1 (0%)
Influenza	10/96 (10.4%)		6/91 (6.6%)		11/73 (15.1%)		1/29 (3.4%)		7/42 (16.7%)		0/1 (0%)
Nasopharyngitis	8/96 (8.3%)		4/91 (4.4%)		12/73 (16.4%)		1/29 (3.4%)		6/42 (14.3%)		0/1 (0%)
Otitis media	1/96 (1%)		0/91 (0%)		1/73 (1.4%)		0/29 (0%)		1/42 (2.4%)		1/1 (100%)
Pharyngitis	3/96 (3.1%)		2/91 (2.2%)		4/73 (5.5%)		0/29 (0%)		3/42 (7.1%)		0/1 (0%)
Tonsillitis	1/96 (1%)		2/91 (2.2%)		4/73 (5.5%)		1/29 (3.4%)		3/42 (7.1%)		0/1 (0%)
Upper respiratory tract infection	8/96 (8.3%)		8/91 (8.8%)		13/73 (17.8%)		1/29 (3.4%)		9/42 (21.4%)		0/1 (0%)
Urinary tract infection	0/96 (0%)		4/91 (4.4%)		1/73 (1.4%)		1/29 (3.4%)		4/42 (9.5%)		0/1 (0%)
Injury, poisoning and procedural complications
Ligament sprain	0/96 (0%)		3/91 (3.3%)		0/73 (0%)		0/29 (0%)		3/42 (7.1%)		0/1 (0%)
Investigations
Alanine aminotransferase increased	9/96 (9.4%)		5/91 (5.5%)		9/73 (12.3%)		2/29 (6.9%)		4/42 (9.5%)		1/1 (100%)
Aspartate aminotransferase increased	7/96 (7.3%)		3/91 (3.3%)		8/73 (11%)		1/29 (3.4%)		2/42 (4.8%)		1/1 (100%)
Blood creatinine increased	8/96 (8.3%)		2/91 (2.2%)		9/73 (12.3%)		1/29 (3.4%)		3/42 (7.1%)		0/1 (0%)
Ejection fraction decreased	0/96 (0%)		0/91 (0%)		0/73 (0%)		0/29 (0%)		1/42 (2.4%)		1/1 (100%)
Electrocardiogram QT prolonged	0/96 (0%)		1/91 (1.1%)		1/73 (1.4%)		1/29 (3.4%)		3/42 (7.1%)		0/1 (0%)
Platelet count increased	2/96 (2.1%)		5/91 (5.5%)		3/73 (4.1%)		6/29 (20.7%)		0/42 (0%)		0/1 (0%)
Protein urine present	11/96 (11.5%)		8/91 (8.8%)		6/73 (8.2%)		1/29 (3.4%)		7/42 (16.7%)		0/1 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	3/96 (3.1%)		1/91 (1.1%)		5/73 (6.8%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/96 (7.3%)		4/91 (4.4%)		5/73 (6.8%)		2/29 (6.9%)		2/42 (4.8%)		1/1 (100%)
Back pain	7/96 (7.3%)		4/91 (4.4%)		7/73 (9.6%)		1/29 (3.4%)		2/42 (4.8%)		0/1 (0%)
Osteoporosis	5/96 (5.2%)		2/91 (2.2%)		3/73 (4.1%)		1/29 (3.4%)		2/42 (4.8%)		1/1 (100%)
Nervous system disorders
Headache	5/96 (5.2%)		5/91 (5.5%)		7/73 (9.6%)		2/29 (6.9%)		4/42 (9.5%)		0/1 (0%)
Psychiatric disorders
Depression	2/96 (2.1%)		1/91 (1.1%)		4/73 (5.5%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	4/96 (4.2%)		2/91 (2.2%)		5/73 (6.8%)		0/29 (0%)		2/42 (4.8%)		0/1 (0%)
Dyspnoea	4/96 (4.2%)		3/91 (3.3%)		1/73 (1.4%)		0/29 (0%)		3/42 (7.1%)		0/1 (0%)
Nasal congestion	1/96 (1%)		1/91 (1.1%)		1/73 (1.4%)		0/29 (0%)		3/42 (7.1%)		0/1 (0%)
Oropharyngeal pain	6/96 (6.3%)		2/91 (2.2%)		6/73 (8.2%)		0/29 (0%)		5/42 (11.9%)		1/1 (100%)
Skin and subcutaneous tissue disorders
Rash	4/96 (4.2%)		0/91 (0%)		4/73 (5.5%)		0/29 (0%)		1/42 (2.4%)		0/1 (0%)
Urticaria	3/96 (3.1%)		3/91 (3.3%)		4/73 (5.5%)		3/29 (10.3%)		2/42 (4.8%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety

Results Point of Contact

Name/Title	Study Director
Organization	Novartis Pharnaceuticals
Phone	862-778-8300
Email	trialandresults.registries@novartis.com

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT00600938

Other Study ID Numbers:

CICL670A2206
2007-000766-20

First Posted:

Jan 25, 2008

Last Update Posted:

Aug 27, 2014

Last Verified:

Aug 1, 2014

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

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