THETIS: Efficacy and Safety Study of Deferasirox in Patients With Non-transfusion Dependent Thalassemia

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01709838
• Collaborator: (none)
• Enrollment: 134
• Locations: 11
• Arm: 1
• Actual Duration (Months): 73.4
• Patients Per Site: 12.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Assessed the efficacy of deferasirox in patients with non-transfusion dependent thalassemia based on change in liver iron concentration from baseline after 52 weeks of treatment. Provided further assessment of the long-term efficacy and safety of deferasirox in NTDT patients with iron overload (LIC ≥ 5 mg Fe/g liver dw and SF ≥ 300 ng/mL) for up to 260 weeks.

Condition or Disease	Intervention/Treatment	Phase
Non-transfusion Dependent Thalassemia	Drug: deferasirox	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Multi-center, Efficacy and Safety Study of Deferasirox in Iron Overloaded Patients With Non-transfusion Dependent Thalassemia
• Actual Study Start Date: Dec 6, 2012
• Actual Primary Completion Date: Jan 3, 2015
• Actual Study Completion Date: Jan 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: Deferasirox All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).	Drug: deferasirox; Deferasirox dispersible tablets at strengths of 125 mg, 250 mg, and 500 mg were administered by oral daily dosing.; Other Names: ICL670

Outcome Measures

Primary Outcome Measures

1. Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline [Baseline, 52 weeks]

   Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment

Secondary Outcome Measures

1. Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw [5 years]

   The percentage of participants with baseline LIC>15 mg Fe/g dw achieving an LIC <5 mg Fe/g dw during the study

2. Time to Achieving LIC <5 mg Fe/g dw [5 years]

   Time to achieving LIC <5 mg Fe/g dw for participants with baseline LIC>15 mg Fe/g dw during the study

3. Time From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period [post-baseline, up to 260 weeks]

   Time from the target LIC <3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period

4. Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) [Baseline, 52, 104 & 156 Weeks]

   The SF-36 is a self-administered questionnaire for adults (from 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, General health perceptions, Vitality, Social functioning, Role limitations due to emotional problems and General mental health . The higher values indicate a better evaluation of health. Range: 0 to 100 [0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)].

5. Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) [Baseline, 52, 104 & 156 Weeks]

   The PedsQL™ is a modular approach to measuring health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL™ Generic Core Scales encompass the essential core domains for pediatric HRQOL measurement: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). The Generic Core Scales are designed to enable comparisons across patient and healthy populations. The higher values indicate a better evaluation of health. Range: 0 to 100 [0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)].

6. Absolute Change in LIC From Baseline Over Time [24, 52, 76, 104, 128, 156, 180, 208, 232, 260 Weeks]

   Absolute change in serum ferritin from baseline over time up to 260 weeks

7. Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up) [Baseline, End of Study (EOS): Week 260 + 30 days follow up]

   Correlation between serum ferritin and LIC is assessed using scatter plots with pearson correlation coefficient and simple linear model.

8. Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up) [Week 24, End of Study (EOS): Week 260 + 30 days follow up]

   Correlation for absolute change between LIC and serum ferritin was assessed using scatter plots with pearson correlation coefficient and simple linear model.

9. Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome [Baseline, 52 Weeks]

   Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment by underlying NTDT syndrome. The 4 underlying disease types: Beta-thalassemia intermedia (N =69), HbE beta-thalassemia (N = 24), Alpha-thalassemia intermedia (HbH disease) (N = 40), Other, specify (N = 1)

10. Absolute Change in Serum Ferritin From Baseline After 52 Weeks [Baseline, 52 weeks]

    Absolute change in serum ferritin from baseline after 52 weeks of treatment

11. PK Parameters: AUCtau [pre-dose (0 hour), and at 2, and 4 hours at Week 4]

    The pharmacokinetic parameter, AUCtau was determined using non-compartmental method(s) for deferasirox and its iron complex. AUC=area under the concentration-time curve during a dosing interval at steady state (amount × time × volume).

12. PK Parameters: Cmax [pre-dose (0 hour), and at 2, and 4 hours at Week 4]

    The pharmacokinetic parameter, Cmax, was determined using non-compartmental method(s) for deferasirox and its iron complex. Cmax (maximum/peak plasma drug concentration after drug administration)=amount × volume

13. PK Parameters: Tmax [pre-dose (0 hour), and at 2, and 4 hours at Week 4]

    The pharmacokinetic parameter, Tmax, may be determined using non-compartmental method(s) for deferasirox and its iron complex. Tmax=time to reach maximum/peak concentration following drug administration.

14. Plasma Pharmacokinetics (PK) Deferasirox Concentrations [Weeks 12 & 24: pre-dose (0hr), 2hr & 4hr post-dose]

    Blood samples for PK evaluation were collected for a sub-group of patients. The patient had to have been on treatment without dose adjustment or treatment interruption (for any reason) for at least 4 consecutive days prior to scheduled PK sampling visit. If there was a dosage change or interruption within 4 days of the visit, no PK blood samples was collected, and an appropriate comment had to be made on the PK CRF page.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Non-transfusion dependent congenital or chronic anemia inclusive of beta-thalassemia intermedia, HbE beta-thalassemia or alpha-thalassemia intermedia (HbH disease)/ Liver iron concentration >/= 5 mg Fe/g dw Serum Ferritin >/= 300 ng/mL

Exclusion Criteria:

HbS-beta Thalassemia, anticipated regular transfusion program during the study, blood transfusion 6 months prior to study start, significant proteinuria, creatinine clearance </= 40 ml/min, serum creatinine > ULN, ALT >5 x ULN, active hepatitis B or C, cirrhosis

Pediatrics Only:

A patient's weight of at least 20 kg is required to allow dosing of 5 mg/kg with one tablet of 125 mg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Nanning	Guangxi	China	530021
2	Novartis Investigative Site	Goudi-Athens	GR	Greece	115 27
3	Novartis Investigative Site	Cagliari	CA	Italy	09121
4	Novartis Investigative Site	Milano	MI	Italy	20122
5	Novartis Investigative Site	Hazmiyeh	Beirut	Lebanon	PO BOX 213
6	Novartis Investigative Site	Bangkok		Thailand	10700
7	Novartis Investigative Site	Tunis		Tunisia	1006
8	Novartis Investigative Site	Adana		Turkey	01330
9	Novartis Investigative Site	Istanbul		Turkey	34093
10	Novartis Investigative Site	Izmir		Turkey	35040
11	Novartis Investigative Site	London		United Kingdom	NW1 2PJ

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 23, 2019
• Study Protocol - Sep 4, 2014

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01709838
• Other Study ID Numbers: CICL670E2419; 2012-000650-64
• First Posted: Oct 18, 2012
• Last Update Posted: Oct 2, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Non-transfusion dependent thalassemia; NTDT; deferasirox; ICL670; LIC; Liver Iron Concentration
• Additional relevant MeSH terms: Thalassemia; Deferasirox

Study Results

Participant Flow

Recruitment Details	At least 117 patients were planned to be enrolled; 134 patients were enrolled.
Pre-assignment Detail	At least 117 patients were planned to be enrolled; 134 patients were enrolled.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Period Title: Overall Study
STARTED	134
COMPLETED	67
NOT COMPLETED	67

Baseline Characteristics

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Overall Participants	134
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.0 (11.10)
Age, Customized (participants) [Number]
< 18 years	25 18.7%
18 - < 50 years	104 77.6%
50 - < 65 years	5 3.7%
Sex: Female, Male (Count of Participants)
Female	58 43.3%
Male	76 56.7%
Race/Ethnicity, Customized (Number) [Number]
Asian	85 63.4%
Caucasian	48 35.8%
Other	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline
Description	Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
Mean (Standard Deviation) [mg Fe/g dw]	-6.68 (7.018)

2. Secondary Outcome

Title	Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw
Description	The percentage of participants with baseline LIC>15 mg Fe/g dw achieving an LIC <5 mg Fe/g dw during the study
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
Number [percentage of participants]	51.0 38.1%

3. Secondary Outcome

Title	Time to Achieving LIC <5 mg Fe/g dw
Description	Time to achieving LIC <5 mg Fe/g dw for participants with baseline LIC>15 mg Fe/g dw during the study
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
Median (95% Confidence Interval) [months]	36.3

4. Secondary Outcome

Title	Time From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period
Description	Time from the target LIC <3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period
Time Frame	post-baseline, up to 260 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
Median (95% Confidence Interval) [days]	27.4

5. Secondary Outcome

Title	Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2)
Description	The SF-36 is a self-administered questionnaire for adults (from 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, General health perceptions, Vitality, Social functioning, Role limitations due to emotional problems and General mental health . The higher values indicate a better evaluation of health. Range: 0 to 100 [0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)].
Time Frame	Baseline, 52, 104 & 156 Weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	105
Physical Functioning Week 52	-0.5 (5.5)
Physical Functioning Week 104	-0.7 (4.9)
Physical Functioning Week 156	0.6 (6.1)
Role Physical Week 52	0.9 (9.1)
Role Physical Week 104	-1.0 (10.2)
Role Physical Week 156	1.0 (10.9)
Bodily Pain Week 52	-0.0 (11.6)
Bodily Pain Week 104	-1.3 (10.8)
General Health Week 52	-2.3 (9.1)
Bodily Pain Week 156	0.9 (12.2)
General Health Pain Week 104	-1.9 (9.2)
General Health Week 156	-1.1 (8.6)
Vitality Week 52	1.1 (9.7)
Vitality Week 104	-0.2 (8.7)
Vitality Week 156	2.1 (9.6)
Social Functioning Week 52	0.9 (9.8)
Social Functioning Week 104	-1.2 (9.6)
Social Functioning Week 156	1.6 (10.6)
Role Emotional Week 52	-0.1 (11.3)
Role Emotional Week 104	-2.5 (12.2)
Role Emotional Week 156	0.7 (11.2)
Mental Health Week 52	1.5 (11.7)
Mental Health Week 104	-0.6 (11.4)
Mental Health Week 156	2.8 (10.9)
Physical Component Week 52	-0.8 (7.2)
Physical Component Week 104	-1.0 (7.4)
Physical Component Week 156	-0.1 (7.9)
Mental Component Week 104	-1.3 (11.1)
Mental Component Week 52	1.1 (10.9)
Mental Component Week 156	2.2 (10.8)
SF6D Health Utility Index Week 52	0.0 (0.1)
SF6D Health Utility Index Week 104	-0.0 (0.1)
SF6D Health Utility Index Week 156	0.0 (0.1)

6. Secondary Outcome

Title	Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™)
Description	The PedsQL™ is a modular approach to measuring health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL™ Generic Core Scales encompass the essential core domains for pediatric HRQOL measurement: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). The Generic Core Scales are designed to enable comparisons across patient and healthy populations. The higher values indicate a better evaluation of health. Range: 0 to 100 [0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)].
Time Frame	Baseline, 52, 104 & 156 Weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	16
Physical Functioning - Teenager Wk 52	2.3 (13.7)
Physical Functioning - Teenager Wk 104	1.0 (19.3)
Physical Functioning - Teenager Wk 156	-0.9 (15.4)
Emotional Functioning - Teenager Wk 52	0.7 (17.8)
Emotional Functioning - Teenager Wk 104	3.1 (27.6)
Emotional Functioning - Teenager Wk 156	10.9 (25.9)
Social Functioning - Teenager Wk 52	-9.3 (17.5)
Social Functioning - Teenager Wk 104	-10.0 (17.8)
Social Functioning - Teenager Wk 156	-5.0 (20.1)
School Functioning - Teenager Wk 52	0.7 (12.4)
School Functioning - Teenager Wk 104	-3.8 (16.4)
School Functioning - Teenager Wk 156	1.0 (21.4)
Physical Health - Teenager Wk 52	2.3 (13.7)
Physical Health - Teenager Wk 104	1.0 (19.3)
Physical Health - Teenager Wk 156	-0.9 (15.4)
Psychosocial Health - Teenager Wk 52	-3.3 (13.0)
Psychosocial Health - Teenager Wk 104	-4.0 (16.9)
Psycholosocial Health - Teenager Wk 156	2.0 (19.1)
Total Score - Teenager Wk 52	-1.0 (10.6)
Total Score - Teenager Wk 104	-1.9 (14.4)
Total Score - Teenager Wk 156	1.2 (15.8)
Physical Functioning - Parent Wk 52	-2.9 (19.0)
Physical Functioning - Parent Wk 104	0.0 (18.6)
Physical Functioning - Parent Wk 156	-0.3 (15.6)
Emotional Functioning - Parent Wk 52	-8.7 (19.1)
Emotional Functioning - Parent Wk 104	-3.8 (20.8)
Emotional Functioning - Parent Wk 156	2.0 (20.6)
Social Functioning - Parent Wk 52	-3.7 (15.5)
Social Functioning - Parent Wk 104	-4.6 (18.0)
Social Functioning - Parent Wk 156	-6.0 (20.9)
School Functioning - Parent Wk 52	-3.6 (20.6)
School Functioning - Parent Wk 104	0.0 (11.7)
School Functioning - Parent Wk 156	-0.6 (21.1)
Physical Health - Parent Wk 52	-2.9 (19.0)
Physical Health - Parent Wk 104	0.0 (18.6)
Physical Health - Parent Wk 156	-0.3 (15.6)
Psychosocial Health - Parent Wk 52	-5.5 (15.0)
Psychosocial Health - Parent Wk 104	-3.2 (12.3)
Psychosocial Health - Parent Wk 156	-1.8 (14.1)
Total Score - Parent Wk 52	-4.6 (14.8)
Total Score - Parent Wk 104	-1.9 (12.0)
Total Score - Parent Wk 156	-1.1 (12.9)

7. Secondary Outcome

Title	Absolute Change in LIC From Baseline Over Time
Description	Absolute change in serum ferritin from baseline over time up to 260 weeks
Time Frame	24, 52, 76, 104, 128, 156, 180, 208, 232, 260 Weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
Week 24	-3.67 (3.778)
Week 52	-7.02 (7.132)
Week 76	-8.93 (8.922)
Week 104	-9.63 (9.474)
Week 128	-10.03 (9.445)
Week 156	-10.20 (9.746)
Week 180	-9.94 (9.838)
Week 208	-10.04 (10.010)
Week 232	-10.58 (10.045)
Week 260	-10.57 (10.366)

8. Secondary Outcome

Title	Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up)
Description	Correlation between serum ferritin and LIC is assessed using scatter plots with pearson correlation coefficient and simple linear model.
Time Frame	Baseline, End of Study (EOS): Week 260 + 30 days follow up

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
At Baseline	0.730
Change from Baseline at EOS	0.531

9. Secondary Outcome

Title	Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up)
Description	Correlation for absolute change between LIC and serum ferritin was assessed using scatter plots with pearson correlation coefficient and simple linear model.
Time Frame	Week 24, End of Study (EOS): Week 260 + 30 days follow up

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
Week 24	0.299
Change from Baseline at EOS	0.740

10. Secondary Outcome

Title	Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome
Description	Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment by underlying NTDT syndrome. The 4 underlying disease types: Beta-thalassemia intermedia (N =69), HbE beta-thalassemia (N = 24), Alpha-thalassemia intermedia (HbH disease) (N = 40), Other, specify (N = 1)
Time Frame	Baseline, 52 Weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
Beta-thalassemia intermedia	-6.11 (6.481)
HbE beta-thalassemia	-6.18 (7.572)
Alpha-thalassemia intermedia (HbH disease)	-7.97 (7.652)
Other, specify	-6.00 (NA)

11. Secondary Outcome

Title	Absolute Change in Serum Ferritin From Baseline After 52 Weeks
Description	Absolute change in serum ferritin from baseline after 52 weeks of treatment
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	134
Mean (Standard Deviation) [ng/mL]	-494.64 (760.782)

12. Secondary Outcome

Title	PK Parameters: AUCtau
Description	The pharmacokinetic parameter, AUCtau was determined using non-compartmental method(s) for deferasirox and its iron complex. AUC=area under the concentration-time curve during a dosing interval at steady state (amount × time × volume).
Time Frame	pre-dose (0 hour), and at 2, and 4 hours at Week 4

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients from FAS who had evaluable PK data.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	22
Geometric Mean (Geometric Coefficient of Variation) [hr*umol/L]	678.2 (61.9)

13. Secondary Outcome

Title	PK Parameters: Cmax
Description	The pharmacokinetic parameter, Cmax, was determined using non-compartmental method(s) for deferasirox and its iron complex. Cmax (maximum/peak plasma drug concentration after drug administration)=amount × volume
Time Frame	pre-dose (0 hour), and at 2, and 4 hours at Week 4

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients from FAS who had evaluable PK data.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	22
Geometric Mean (Geometric Coefficient of Variation) [umol/L]	53.367 (60.960)

14. Secondary Outcome

Title	PK Parameters: Tmax
Description	The pharmacokinetic parameter, Tmax, may be determined using non-compartmental method(s) for deferasirox and its iron complex. Tmax=time to reach maximum/peak concentration following drug administration.
Time Frame	pre-dose (0 hour), and at 2, and 4 hours at Week 4

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients from FAS who had evaluable PK data.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	22
Geometric Mean (Geometric Coefficient of Variation) [hr]	2.5131 (33.9321)

15. Secondary Outcome

Title	Plasma Pharmacokinetics (PK) Deferasirox Concentrations
Description	Blood samples for PK evaluation were collected for a sub-group of patients. The patient had to have been on treatment without dose adjustment or treatment interruption (for any reason) for at least 4 consecutive days prior to scheduled PK sampling visit. If there was a dosage change or interruption within 4 days of the visit, no PK blood samples was collected, and an appropriate comment had to be made on the PK CRF page.
Time Frame	Weeks 12 & 24: pre-dose (0hr), 2hr & 4hr post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients from FAS who had evaluable PK data.

Arm/Group Title	Deferasirox
Arm/Group Description	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
Measure Participants	22
4 weeks: 0hr pre-dose	6.513 (75.891)
4 weeks: 2hr post-dose	48.556 (58.006)
4 weeks: 4hr post-dose	44.652 (69.392)

Adverse Events

Time Frame	Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 63.2 months.
Adverse Event Reporting Description	All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 7 years.
Arm/Group Title	Chinese		Non-Chinese		All Patients
Arm/Group Description	This group was comprised of Chinese participants only		This group was comprised of non- Chinese participants only		This group was comprised of all patients: Chinese and non-Chinese participants
All Cause Mortality
	Chinese		Non-Chinese		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/68 (2.9%)		0/66 (0%)		2/134 (1.5%)
Serious Adverse Events
	Chinese		Non-Chinese		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/68 (22.1%)		30/66 (45.5%)		45/134 (33.6%)
Blood and lymphatic system disorders
Anaemia	2/68 (2.9%)		4/66 (6.1%)		6/134 (4.5%)
Extramedullary haemopoiesis	0/68 (0%)		2/66 (3%)		2/134 (1.5%)
Haemolysis	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Haemolytic anaemia	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Hypersplenism	2/68 (2.9%)		0/66 (0%)		2/134 (1.5%)
Splenomegaly	2/68 (2.9%)		0/66 (0%)		2/134 (1.5%)
Thrombocytosis	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Cardiac disorders
Atrial fibrillation	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Cardiac failure	2/68 (2.9%)		0/66 (0%)		2/134 (1.5%)
Sinus tachycardia	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Eye disorders
Cataract	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Gastrointestinal disorders
Abdominal pain	0/68 (0%)		2/66 (3%)		2/134 (1.5%)
Abdominal pain upper	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Diarrhoea	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Enteritis	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Inguinal hernia	1/68 (1.5%)		1/66 (1.5%)		2/134 (1.5%)
Pancreatitis	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Peptic ulcer	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Superior mesenteric artery syndrome	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
General disorders
Fatigue	0/68 (0%)		2/66 (3%)		2/134 (1.5%)
Generalised oedema	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Malaise	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Pyrexia	0/68 (0%)		3/66 (4.5%)		3/134 (2.2%)
Hepatobiliary disorders
Biliary colic	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Cholecystitis	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Cholecystitis acute	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Cholelithiasis	1/68 (1.5%)		3/66 (4.5%)		4/134 (3%)
Hepatic fibrosis	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Jaundice	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Infections and infestations
Bronchitis	1/68 (1.5%)		1/66 (1.5%)		2/134 (1.5%)
Epididymitis	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Gastroenteritis	0/68 (0%)		4/66 (6.1%)		4/134 (3%)
Lung infection	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Pharyngitis	0/68 (0%)		2/66 (3%)		2/134 (1.5%)
Pharyngotonsillitis	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Pneumonia	3/68 (4.4%)		4/66 (6.1%)		7/134 (5.2%)
Pyelonephritis acute	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Sepsis	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Tonsillitis	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Upper respiratory tract infection	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Urinary tract infection	0/68 (0%)		3/66 (4.5%)		3/134 (2.2%)
Varicella	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Injury, poisoning and procedural complications
Compression fracture	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Fracture	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Limb injury	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Skin laceration	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Spinal compression fracture	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Spinal fracture	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Upper limb fracture	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Metabolism and nutrition disorders
Hyperglycaemic hyperosmolar nonketotic syndrome	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Type 2 diabetes mellitus	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Musculoskeletal and connective tissue disorders
Osteoporosis	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Spinal osteoarthritis	1/68 (1.5%)		0/66 (0%)		1/134 (0.7%)
Tendonitis	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Nervous system disorders
Cerebrovascular accident	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Dizziness	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Dyspnoea	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Pulmonary hypertension	0/68 (0%)		1/66 (1.5%)		1/134 (0.7%)
Other (Not Including Serious) Adverse Events
	Chinese		Non-Chinese		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/68 (38.2%)		58/66 (87.9%)		84/134 (62.7%)
Blood and lymphatic system disorders
Anaemia	0/68 (0%)		5/66 (7.6%)		5/134 (3.7%)
Gastrointestinal disorders
Abdominal discomfort	2/68 (2.9%)		5/66 (7.6%)		7/134 (5.2%)
Abdominal pain	0/68 (0%)		15/66 (22.7%)		15/134 (11.2%)
Abdominal pain upper	0/68 (0%)		9/66 (13.6%)		9/134 (6.7%)
Constipation	0/68 (0%)		4/66 (6.1%)		4/134 (3%)
Dental caries	0/68 (0%)		5/66 (7.6%)		5/134 (3.7%)
Diarrhoea	1/68 (1.5%)		19/66 (28.8%)		20/134 (14.9%)
Dyspepsia	0/68 (0%)		4/66 (6.1%)		4/134 (3%)
Gastritis	0/68 (0%)		5/66 (7.6%)		5/134 (3.7%)
Nausea	2/68 (2.9%)		10/66 (15.2%)		12/134 (9%)
Toothache	0/68 (0%)		7/66 (10.6%)		7/134 (5.2%)
Vomiting	1/68 (1.5%)		11/66 (16.7%)		12/134 (9%)
General disorders
Fatigue	1/68 (1.5%)		12/66 (18.2%)		13/134 (9.7%)
Influenza like illness	0/68 (0%)		7/66 (10.6%)		7/134 (5.2%)
Pyrexia	3/68 (4.4%)		14/66 (21.2%)		17/134 (12.7%)
Hepatobiliary disorders
Cholelithiasis	1/68 (1.5%)		6/66 (9.1%)		7/134 (5.2%)
Infections and infestations
Conjunctivitis	0/68 (0%)		5/66 (7.6%)		5/134 (3.7%)
Gastroenteritis	1/68 (1.5%)		9/66 (13.6%)		10/134 (7.5%)
Influenza	0/68 (0%)		11/66 (16.7%)		11/134 (8.2%)
Pharyngitis	0/68 (0%)		11/66 (16.7%)		11/134 (8.2%)
Tonsillitis	0/68 (0%)		12/66 (18.2%)		12/134 (9%)
Upper respiratory tract infection	7/68 (10.3%)		27/66 (40.9%)		34/134 (25.4%)
Urinary tract infection	2/68 (2.9%)		8/66 (12.1%)		10/134 (7.5%)
Investigations
Blood creatinine increased	1/68 (1.5%)		4/66 (6.1%)		5/134 (3.7%)
Platelet count increased	13/68 (19.1%)		1/66 (1.5%)		14/134 (10.4%)
Urine protein/creatinine ratio increased	0/68 (0%)		6/66 (9.1%)		6/134 (4.5%)
Metabolism and nutrition disorders
Hyperphosphataemia	0/68 (0%)		8/66 (12.1%)		8/134 (6%)
Hyperuricaemia	1/68 (1.5%)		5/66 (7.6%)		6/134 (4.5%)
Vitamin D deficiency	0/68 (0%)		4/66 (6.1%)		4/134 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/68 (0%)		8/66 (12.1%)		8/134 (6%)
Back pain	0/68 (0%)		16/66 (24.2%)		16/134 (11.9%)
Flank pain	0/68 (0%)		4/66 (6.1%)		4/134 (3%)
Myalgia	0/68 (0%)		10/66 (15.2%)		10/134 (7.5%)
Osteoporosis	1/68 (1.5%)		4/66 (6.1%)		5/134 (3.7%)
Pain in extremity	0/68 (0%)		6/66 (9.1%)		6/134 (4.5%)
Nervous system disorders
Dizziness	0/68 (0%)		8/66 (12.1%)		8/134 (6%)
Headache	0/68 (0%)		27/66 (40.9%)		27/134 (20.1%)
Psychiatric disorders
Anxiety	0/68 (0%)		4/66 (6.1%)		4/134 (3%)
Insomnia	0/68 (0%)		5/66 (7.6%)		5/134 (3.7%)
Renal and urinary disorders
Dysuria	0/68 (0%)		4/66 (6.1%)		4/134 (3%)
Respiratory, thoracic and mediastinal disorders
Cough	0/68 (0%)		8/66 (12.1%)		8/134 (6%)
Dyspnoea	0/68 (0%)		6/66 (9.1%)		6/134 (4.5%)
Nasal congestion	0/68 (0%)		11/66 (16.7%)		11/134 (8.2%)
Oropharyngeal pain	0/68 (0%)		16/66 (24.2%)		16/134 (11.9%)
Productive cough	0/68 (0%)		8/66 (12.1%)		8/134 (6%)
Pulmonary hypertension	0/68 (0%)		5/66 (7.6%)		5/134 (3.7%)
Rhinorrhoea	0/68 (0%)		5/66 (7.6%)		5/134 (3.7%)

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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.