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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02125877
• Collaborator: (none)
• Enrollment: 173
• Locations: 51
• Arms: 2
• Actual Duration (Months): 19.6
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Iron Overload Due to Transfusion-dependant Anemias	Drug: Deferasirox dispersible tablet; Drug: Defearisox film-coated tablet	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 173 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Multicenter, Two Arm, Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
• Actual Study Start Date: Jul 8, 2014
• Actual Primary Completion Date: Feb 24, 2016
• Actual Study Completion Date: Feb 24, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Deferasirox dispersible tablet (DFX-DT) Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Drug: Deferasirox dispersible tablet; Deferasirox DT was provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use.; Other Names: ICL670, DT (dispersible tablet)
Experimental: Deferasirox film-coated tablet (DFX-FCT) Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose	Drug: Defearisox film-coated tablet; Deferasirox FCT was provided as 90 mg, 180 mg and 360 mg film-coated tablets for oral use.; Other Names: ICL670, FCT (film-coated tablet)

Outcome Measures

Primary Outcome Measures

1. Overall Safety as Measured by Frequency of Adverse Events [28 weeks]

   The percentage of participants with adverse events, serious adverse events and deaths was assessed.

2. Overall Safety as Measured by Changes in Laboratory Values From Baseline [baseline (BL), 30 weeks]

   The percentage of participants with post-baseline laboratory values meeting specified criteria for notable/extended range was assessed. The following laboratory parameters were measured: platelet count, absolute neutrophils, serum creatinine , creatinine clearance, urinary protein/urinary creatinine ratio, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Note that within data categories, creat = creatinine, cons = consecutive, ULN = upper limit of normal and urin = urinary.

Secondary Outcome Measures

1. Frequency of Selected Gastro-intestinal (GI) Adverse Events [28 weeks]

   The percentage of participants with any GI adverse event, diarrhea, constipation, nausea, vomiting, abdominal pain was assessed.

2. Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT) [weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)]

   The modified SICT consisted of 13 items that represent 3 domains: adherence, satisfaction and concerns. The adherence domain consisted of 7 items, 6 which were measured using a 5-point response scale and was calculated by summing the 6 items. The score range from 6 to 30 and higher scores indicated worse adherence. The satisfaction domain consisted of 3 items, 2 which were measured using a 5-point response scale and was calculated by summing the 2 items. The score range from 2 to 10 and higher scores indicated worse satisfaction. The concerns domain consisted of 3 items to address any concerns or worries with his/her medication. All 3 items were measured on a 5-point response scale and were calculated by summing the 3 items. The score range from 3 to 15 and higher scores indicated fewer concerns. For all three domains, the meaningful difference between two treatment arms was determined to be 1 point.

3. Palatability Questionnaire Score [weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)]

   The palatability questionnaire consisted of 4 items. The first item measured the taste and aftertaste of the medication and were scored a on a 5-point response scale. The second item offered an additional response option of "no aftertaste". The last 2 items referred to whether the medication was taken, i.e. swallowed or vomited, and how the participant perceived the amount of medication to be taken. The palatability summary score was calculated using a scoring matrix from items 1, 3 and 4 scores and the score ranges from 0 - 11. Higher scores indicated the best palatability. A meaningful difference between two treatment arms was determined to be 1 point.

4. Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary [weeks -1, 4, 8, 12, 16, 20, 24]

   The GI symptom diary consisted of 6 items, five which were scored using a 0 - 10 rating scale with item appropriate anchors to rate the symptom, for example, Pain in your belly: 0 = no pain and 10 = worst pain. The GI diary summary score was created using the 10 point response scale for the 5 items. The GI symptom daily diary had a minimum score of 0 and a maximum score of 50. The weekly average score for the 7 days was calculated for each individual item and the GI summary score was created from these weekly averages. Higher scores indicated worse symptoms. A meaningful difference between two treatment arms was determined to be 0.3 point.

5. Number of Participants With Weekly Average Compliance of Medication Consumption [Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]

   A compliance questionnaire assessed whether the medication was taken. Weekly average compliance was calculated when there were at least four non-missing daily responses.

6. Weekly Dose Violation Rate [weeks 1, 4, 8, 12, 16, 20, 24]

   The dose violation is defined as a dose either missed completely or not taken in accordance with the timing instruction (no later than 12:00 pm. The rate was calculated as [number of dose violations/drug exposure (days)] x 100.

7. Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) [week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose]

   Blood samples were collected to assess AUClast.

8. Observed Maximum Plasma Concentration Following Drug Administration (Cmax) [week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose]

   Blood samples were collected to assess Cmax.

9. Time to Reach the Maximum Plasma Concentration After Drug Administration (Tmax) [week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose]

   Blood samples were collected to assess Tmax.

10. Dererasirox Plasma Concentration [Week 3, day 1, pre-dose (0 hour (h)) and 2 h post-dose; week 13, day 1, pre-dose (0 hour (h)) and 2 h post-dose; and week 21, day 1, pre-dose (0 hour (h)) and 2 h post-dose]

    Blood samples were collected to assess deferasirox concentration. Dose-adjusted calculations are presented: (concentration/actual dose)*20 for participants on DFX-DT and (concentration/actual dose)*14 for participants on DFX-FCT.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Male and female patients aged ≥ 10 years

• Patients with transfusion-dependent thalassemia and iron overload, requiring deferasirox DT at doses of ≥ 30 mg/kg/day as per the investigator's decision OR Patients with very low, low or intermediate (int) risk myelodysplastic syndrome (MDS) and iron overload, requiring deferasirox DT at doses of ≥ 20 mg/kg/day as per the investigator's decision.

• History of transfusion of at least 20 PRBC units and anticipated to be transfused with at least 8 units of PRBCs annually during the study

• Serum ferritin > 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).

Key Exclusion Criteria:

• Creatinine clearance below the contraindication limit in the locally approved prescribing information. Creatinine clearance will be estimated from serum creatinine at screening Visit 1 and screening Visit 2 and the mean value will be used for eligibility criteria.

• Serum creatinine > 1.5 xULN at screening measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).

• ALT (SGPT) > 5xULN, unless LIC confirmed as >10 mg Fe/dw within 6 months prior to screening visit 1.

• Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample at screening Visit 1 or screening Visit 2.

• Patients with significant impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).

• Liver disease with severity of Child-Pugh Class B or C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Orange County Onc Dept	Orange	California	United States	92868-3874
2	Lurie Children's Hospital of Chicago Onc Dept	Chicago	Illinois	United States	60611
3	Children's Hospital Boston Department of Hematology	Boston	Massachusetts	United States	02115
4	Weill Cornell Medical College-Cornell University Onc Dept	New York	New York	United States	10021
5	Children's Hospital of Philadelphia Onc. Dept	Philadelphia	Pennsylvania	United States	19104-4399
6	Novartis Investigative Site	Buenos aires		Argentina	C1221ADC
7	Novartis Investigative Site	Linz		Austria	A-4010
8	Novartis Investigative Site	Wien		Austria	1140
9	Novartis Investigative Site	Lille cedex		France	59020
10	Novartis Investigative Site	Paris		France	75010
11	Novartis Investigative Site	Mannheim	Baden-Württemberg	Germany	68305
12	Novartis Investigative Site	Berlin		Germany	13353
13	Novartis Investigative Site	Dresden		Germany	01307
14	Novartis Investigative Site	Goslar		Germany	38642
15	Novartis Investigative Site	Hannover		Germany	30170
16	Novartis Investigative Site	Leipzig		Germany	04103
17	Novartis Investigative Site	Potsdam		Germany	14467
18	Novartis Investigative Site	Athens	GR	Greece	GR-115 27
19	Novartis Investigative Site	Patra - RIO	GR	Greece	265 04
20	Novartis Investigative Site	Thessaloniki	GR	Greece	546 42
21	Novartis Investigative Site	Brindisi	BR	Italy	72100
22	Novartis Investigative Site	Catania	CT	Italy	95125
23	Novartis Investigative Site	Cona	FE	Italy	44100
24	Novartis Investigative Site	Genova	GE	Italy	16128
25	Novartis Investigative Site	Genova	GE	Italy	16132
26	Novartis Investigative Site	Cagliari	ITA	Italy	09121
27	Novartis Investigative Site	Lecce	LE	Italy	73100
28	Novartis Investigative Site	Milano	MI	Italy	20122
29	Novartis Investigative Site	Milano	MI	Italy	20162
30	Novartis Investigative Site	Palermo	PA	Italy	90127
31	Novartis Investigative Site	Palermo	PA	Italy	90146
32	Novartis Investigative Site	Reggio Calabria	RC	Italy	89100
33	Novartis Investigative Site	Verona	VR	Italy	37126
34	Novartis Investigative Site	Napoli		Italy	80138
35	Novartis Investigative Site	Hazmiyeh	Beirut	Lebanon	PO Box 213
36	Novartis Investigative Site	Kuala Lumpur		Malaysia	50589
37	Novartis Investigative Site	Pulau Pinang		Malaysia	10990
38	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	06726
39	Novartis Investigative Site	Moskow	Russia	Russian Federation	117198
40	Novartis Investigative Site	Dammam		Saudi Arabia	15215
41	Novartis Investigative Site	Dammam		Saudi Arabia	40145
42	Novartis Investigative Site	Jeddah		Saudi Arabia	21589
43	Novartis Investigative Site	Riyadh		Saudi Arabia	11472
44	Novartis Investigative Site	Barcelona		Spain	08041
45	Novartis Investigative Site	Madrid		Spain	28033
46	Novartis Investigative Site	Bangkok		Thailand	10400
47	Novartis Investigative Site	Bangkok		Thailand	10700
48	Novartis Investigative Site	Al Ain - Abu Dhabi		United Arab Emirates
49	Novartis Investigative Site	Dubai		United Arab Emirates	9115
50	Novartis Investigative Site	London		United Kingdom	N19 5NF
51	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: NCT02125877
• Other Study ID Numbers: CICL670F2201
• First Posted: Apr 29, 2014
• Last Update Posted: Jul 25, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Novartis Pharmaceuticals: Iron overload; Chelation; Thalassemia; Myelodysplastic syndrome (MDS); Transfusional hemisiderosis; Deferasirox; ICL670; Dispersible tablet; Film-coated tablet
• Additional relevant MeSH terms: Iron Overload; Deferasirox

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 1:1 ratio.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Period Title: Overall Study
STARTED	86	87
Pharmacokinetic Analysis Set	83	83
Pharmacokinetic Subset A	16	15
Safety Set	86	87
COMPLETED	73	77
NOT COMPLETED	13	10

Baseline Characteristics

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)	Total
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose	Total of all reporting groups
Overall Participants	86	87	173
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	35.1 (18.60)	34.6 (19.97)	34.9 (19.25)
Sex: Female, Male (Count of Participants)
Female	47 54.7%	41 47.1%	88 50.9%
Male	39 45.3%	46 52.9%	85 49.1%

Outcome Measures

1. Primary Outcome

Title	Overall Safety as Measured by Frequency of Adverse Events
Description	The percentage of participants with adverse events, serious adverse events and deaths was assessed.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

The safety set, which included all participants who received at least one dose of study drug, was analyzed.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	86	87
Adverse events	89.5 104.1%	89.7 103.1%
SAEs	15.1 17.6%	18.4 21.1%
Deaths	0 0%	1.1 1.3%

2. Primary Outcome

Title	Overall Safety as Measured by Changes in Laboratory Values From Baseline
Description	The percentage of participants with post-baseline laboratory values meeting specified criteria for notable/extended range was assessed. The following laboratory parameters were measured: platelet count, absolute neutrophils, serum creatinine , creatinine clearance, urinary protein/urinary creatinine ratio, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Note that within data categories, creat = creatinine, cons = consecutive, ULN = upper limit of normal and urin = urinary.
Time Frame	baseline (BL), 30 weeks

Outcome Measure Data

Analysis Population Description

The safety set, which included all participants who received at least one dose of study drug, was analyzed.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	86	87
platelet count, notable range: <100 x 10^9/L	9.3 10.8%	8.0 9.2%
platelet count, extended range: <50 x 10^9/L	3.5 4.1%	5.7 6.6%
absolute neutrophils, notable range: <1.5 x 10^9/L	8.1 9.4%	13.8 15.9%
absolute neut., extended range: <0.5 x 10^9/L	4.7 5.5%	0 0%
serum creat, 2 cons >33% incr. from BL and >ULN	4.7 5.5%	3.4 3.9%
creat clearance, notable range: 2 cons <60mL/min	7.0 8.1%	2.3 2.6%
creat clearance, extended range: 2 cons <40mL/min	2.3 2.7%	2.3 2.6%
urin protein/urin creat ratio, 2 cons >1.0 mg/mg	2.3 2.7%	0 0%
ALT, notable range: >5 x ULN and >2 x BL	1.2 1.4%	1.1 1.3%
ALT, extended range: >10 x ULN and >2 x BL	1.2 1.4%	0 0%
AST, notable range: >5 x ULN and >2 x BL	0 0%	1.1 1.3%
AST, extended range: >10 x ULN and >2 x BL	1.2 1.4%	0 0%

3. Secondary Outcome

Title	Frequency of Selected Gastro-intestinal (GI) Adverse Events
Description	The percentage of participants with any GI adverse event, diarrhea, constipation, nausea, vomiting, abdominal pain was assessed.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

The safety set, which included all participants who received at least one dose of study drug, was analyzed.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	86	87
Any GI adverse event	61.6 71.6%	58.6 67.4%
Abdominal pain	26.7 31%	26.4 30.3%
Constipation	15.1 17.6%	8.0 9.2%
Diarrhea	34.9 40.6%	33.3 38.3%
Nausea	26.7 31%	27.6 31.7%
Vomiting	22.1 25.7%	17.2 19.8%

4. Secondary Outcome

Title	Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
Description	The modified SICT consisted of 13 items that represent 3 domains: adherence, satisfaction and concerns. The adherence domain consisted of 7 items, 6 which were measured using a 5-point response scale and was calculated by summing the 6 items. The score range from 6 to 30 and higher scores indicated worse adherence. The satisfaction domain consisted of 3 items, 2 which were measured using a 5-point response scale and was calculated by summing the 2 items. The score range from 2 to 10 and higher scores indicated worse satisfaction. The concerns domain consisted of 3 items to address any concerns or worries with his/her medication. All 3 items were measured on a 5-point response scale and were calculated by summing the 3 items. The score range from 3 to 15 and higher scores indicated fewer concerns. For all three domains, the meaningful difference between two treatment arms was determined to be 1 point.
Time Frame	weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)

Outcome Measure Data

Analysis Population Description

The safety set, which included all participants who received at least one dose of study drug, was considered for the analysis. However, only participants with values at the given week were included in the analysis for that week.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	86	87
week 2, adherence (n=70,70)	10.3 (3.80)	7.6 (2.14)
week 2, satisfaction/preference (n=70,70)	5.2 (2.24)	2.8 (1.37)
week 2, concerns (n=70,70)	12.9 (2.94)	13.8 (2.02)
week 3, adherence (n=58,51)	10.9 (4.09)	7.7 (2.06)
week 3, satisfaction/preference (n=58,51)	5.4 (2.22)	2.6 (1.05)
week 3, concerns (n=58,51)	12.4 (2.73)	14.0 (1.49)
week 13, adherence (n=59,64)	11.2 (3.56)	7.8 (2.05)
week 13, satisfaction/preference (n=59,64)	5.4 (2.14)	2.9 (1.54)
week 13, concerns (n=59,64)	12.7 (2.50)	13.6 (1.87)
week 24, adherence (n=63,60)	12.5 (5.32)	7.5 (2.41)
week 24, satisfaction/preference (n=63,60)	5.8 (2.28)	2.9 (1.58)
week 24, concerns (n=63,60)	11.8 (3.07)	13.7 (1.84)

5. Secondary Outcome

Title	Palatability Questionnaire Score
Description	The palatability questionnaire consisted of 4 items. The first item measured the taste and aftertaste of the medication and were scored a on a 5-point response scale. The second item offered an additional response option of "no aftertaste". The last 2 items referred to whether the medication was taken, i.e. swallowed or vomited, and how the participant perceived the amount of medication to be taken. The palatability summary score was calculated using a scoring matrix from items 1, 3 and 4 scores and the score ranges from 0 - 11. Higher scores indicated the best palatability. A meaningful difference between two treatment arms was determined to be 1 point.
Time Frame	weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)

Outcome Measure Data

Analysis Population Description

The safety set, which included all participants who received at least one dose of study drug, was considered for the analysis. However, only participants with values at the given week were included in the analysis for that week.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	86	87
week 2 (n=69,70)	9.0 (3.01)	10.8 (0.50)
week 3 (n=57,51)	8.8 (3.01)	10.8 (0.45)
week 13 (n=59,62)	9.3 (2.84)	10.8 (1.16)
week 24 (n=63,60)	8.8 (3.10)	10.9 (0.34)

6. Secondary Outcome

Title	Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
Description	The GI symptom diary consisted of 6 items, five which were scored using a 0 - 10 rating scale with item appropriate anchors to rate the symptom, for example, Pain in your belly: 0 = no pain and 10 = worst pain. The GI diary summary score was created using the 10 point response scale for the 5 items. The GI symptom daily diary had a minimum score of 0 and a maximum score of 50. The weekly average score for the 7 days was calculated for each individual item and the GI summary score was created from these weekly averages. Higher scores indicated worse symptoms. A meaningful difference between two treatment arms was determined to be 0.3 point.
Time Frame	weeks -1, 4, 8, 12, 16, 20, 24

Outcome Measure Data

Analysis Population Description

The safety set, which included all participants who received at least one dose of study drug, was considered for the analysis. However, only participants with values at the given week were included in the analysis for that week.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	86	87
week -1 (n=69,65)	1.4 (2.10)	1.9 (3.69)
week 4 (n=60,64)	1.8 (3.49)	1.1 (2.15)
week 8 (n=59,51)	1.4 (2.45)	1.1 (2.16)
week 12 (n=51,45)	1.7 (3.16)	1.0 (1.78)
week 16 (n=48,41)	1.9 (3.75)	0.9 (1.92)
week 20 (n40,39)	1.5 (3.27)	0.9 (1.44)
week 24 (n32,26)	1.5 (3.29)	1.2 (1.89)

7. Secondary Outcome

Title	Number of Participants With Weekly Average Compliance of Medication Consumption
Description	A compliance questionnaire assessed whether the medication was taken. Weekly average compliance was calculated when there were at least four non-missing daily responses.
Time Frame	Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Outcome Measure Data

Analysis Population Description

The safety set, which included all participants who received at least one dose of study drug, was analyzed.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	86	87
week 1	56 65.1%	53 60.9%
week 2	64 74.4%	64 73.6%
week 3	62 72.1%	56 64.4%
week 4	58 67.4%	58 66.7%
week 5	56 65.1%	58 66.7%
week 6	62 72.1%	51 58.6%
week 7	55 64%	48 55.2%
week 8	56 65.1%	46 52.9%
week 9	53 61.6%	45 51.7%
week 10	52 60.5%	46 52.9%
week 11	50 58.1%	42 48.3%
week 12	50 58.1%	41 47.1%
week 13	49 57%	47 54%
week 14	51 59.3%	42 48.3%
week 15	48 55.8%	42 48.3%
week 16	48 55.8%	40 46%
week 17	43 50%	39 44.8%
week 18	43 50%	38 43.7%
week 19	40 46.5%	37 42.5%
week 20	40 46.5%	36 41.4%
week 21	39 45.3%	36 41.4%
week 22	38 44.2%	34 39.1%
week 23	36 41.9%	33 37.9%
week 24	30 34.9%	24 27.6%

8. Secondary Outcome

Title	Weekly Dose Violation Rate
Description	The dose violation is defined as a dose either missed completely or not taken in accordance with the timing instruction (no later than 12:00 pm. The rate was calculated as [number of dose violations/drug exposure (days)] x 100.
Time Frame	weeks 1, 4, 8, 12, 16, 20, 24

Outcome Measure Data

Analysis Population Description

The safety set, which included all participants who received at least one dose of study drug, was considered for the analysis. However, only participants with values at the given week were included in the analysis for that week.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	86	87
week 1 (n=56,53)	17.7 (31.04)	15.8 (29.42)
week 4 (n=58,58)	15.8 (32.51)	6.7 (15.45)
week 8 (n=56,46)	18.0 (35.38)	8.4 (22.17)
week 12 (n=50,41)	15.7 (34.22)	10.7 (22.63)
week 16 (n=48,40)	13.5 (31.08)	10.0 (24.5)
week 20 (n=40,36)	22.6 (38.38)	11.3 (26.67)
week 24 (n=30,24)	17.1 (34.26)	10.1 (25.47)

9. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Description	Blood samples were collected to assess AUClast.
Time Frame	week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic subset A analysis set was considered for the analysis, but only participants with non-missing values were analyzed.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	16	15
week1 (n=14,15)	1110 (495)	1040 (405)
week 3 (n=13,15)	1590 (540)	2110 (987)

10. Secondary Outcome

Title	Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
Description	Blood samples were collected to assess Cmax.
Time Frame	week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic subset A analysis set was considered for the analysis, but only participants with non-missing values were analyzed

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	16	15
week 1 (n=14,15)	74.6 (30.7)	79.3 (23.5)
week 3 (n=14,15)	118 (82.3)	139 (57.2)

11. Secondary Outcome

Title	Time to Reach the Maximum Plasma Concentration After Drug Administration (Tmax)
Description	Blood samples were collected to assess Tmax.
Time Frame	week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic subset A analysis set was considered for the analysis, but only participants with non-missing values were analyzed

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	16	15
week 1 (n=14,15)	3.57	2.00
week 3 (n=14,15)	2.85	2.02

12. Secondary Outcome

Title	Dererasirox Plasma Concentration
Description	Blood samples were collected to assess deferasirox concentration. Dose-adjusted calculations are presented: (concentration/actual dose)*20 for participants on DFX-DT and (concentration/actual dose)*14 for participants on DFX-FCT.
Time Frame	Week 3, day 1, pre-dose (0 hour (h)) and 2 h post-dose; week 13, day 1, pre-dose (0 hour (h)) and 2 h post-dose; and week 21, day 1, pre-dose (0 hour (h)) and 2 h post-dose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic analysis set for all participants was considered for this analysis, but only participants with non-missing values were included in the analysis.

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)	Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.	Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Measure Participants	83	83
week 3, pre-dose (n=63,70)	39.6 (48.4)	27.3 (20.4)
week 3, 2 hours post-dose (n=67,76)	80.8 (52.2)	95.5 (53.0)
week 13, pre-dose (n=69.56)	37.1 (37.8)	31.3 (22.9)
week 13, 2 hours post-dose (n=74,59)	78.7 (39.5)	92.5 (39.1)
week 21, pre-dose (n=54,59)	46.6 (46.4)	43.1 (36.8)
week 21, 2 hours post-dose (n=59,64)	89.8 (59.3)	105 (51.2)

Adverse Events

Arm/Group Title	Deferasirox Dispersible Tablet (DFX-DT)		Deferasirox Film-coated Tablet (DFX-FCT)
Arm/Group Description	Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.		Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
All Cause Mortality
	Deferasirox Dispersible Tablet (DFX-DT)		Deferasirox Film-coated Tablet (DFX-FCT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Deferasirox Dispersible Tablet (DFX-DT)		Deferasirox Film-coated Tablet (DFX-FCT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/86 (15.1%)		16/87 (18.4%)
Blood and lymphatic system disorders
Anaemia	0/86 (0%)		1/87 (1.1%)
Autoimmune haemolytic anaemia	1/86 (1.2%)		0/87 (0%)
Febrile neutropenia	0/86 (0%)		1/87 (1.1%)
Haemolysis	1/86 (1.2%)		0/87 (0%)
Cardiac disorders
Atrial fibrillation	1/86 (1.2%)		0/87 (0%)
Cardiac failure acute	1/86 (1.2%)		0/87 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/86 (1.2%)		0/87 (0%)
Anal fissure	1/86 (1.2%)		0/87 (0%)
Ascites	1/86 (1.2%)		0/87 (0%)
Diarrhoea	0/86 (0%)		2/87 (2.3%)
Dysphagia	1/86 (1.2%)		0/87 (0%)
Neutropenic colitis	0/86 (0%)		1/87 (1.1%)
Rectal haemorrhage	1/86 (1.2%)		0/87 (0%)
Vomiting	1/86 (1.2%)		0/87 (0%)
General disorders
Face oedema	1/86 (1.2%)		0/87 (0%)
Oedema	1/86 (1.2%)		0/87 (0%)
Pyrexia	0/86 (0%)		1/87 (1.1%)
Hepatobiliary disorders
Biliary colic	0/86 (0%)		1/87 (1.1%)
Cholecystitis	1/86 (1.2%)		0/87 (0%)
Hepatitis	0/86 (0%)		1/87 (1.1%)
Infections and infestations
Appendicitis	1/86 (1.2%)		0/87 (0%)
Brucellosis	0/86 (0%)		1/87 (1.1%)
Gastroenteritis	0/86 (0%)		1/87 (1.1%)
Pneumonia	0/86 (0%)		1/87 (1.1%)
Post procedural pneumonia	1/86 (1.2%)		0/87 (0%)
Respiratory tract infection	1/86 (1.2%)		0/87 (0%)
Sepsis	0/86 (0%)		2/87 (2.3%)
Septic shock	0/86 (0%)		1/87 (1.1%)
Subcutaneous abscess	1/86 (1.2%)		0/87 (0%)
Viral infection	1/86 (1.2%)		0/87 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/86 (0%)		2/87 (2.3%)
Delayed haemolytic transfusion reaction	1/86 (1.2%)		0/87 (0%)
Lower limb fracture	1/86 (1.2%)		0/87 (0%)
Patella fracture	0/86 (0%)		1/87 (1.1%)
Investigations
Ejection fraction decreased	1/86 (1.2%)		0/87 (0%)
Urine protein/creatinine ratio increased	0/86 (0%)		1/87 (1.1%)
Metabolism and nutrition disorders
Decreased appetite	1/86 (1.2%)		0/87 (0%)
Dehydration	1/86 (1.2%)		0/87 (0%)
Hyperglycaemia	0/86 (0%)		1/87 (1.1%)
Musculoskeletal and connective tissue disorders
Back pain	1/86 (1.2%)		0/87 (0%)
Joint effusion	0/86 (0%)		1/87 (1.1%)
Neck pain	1/86 (1.2%)		0/87 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	0/86 (0%)		1/87 (1.1%)
Leukaemia	0/86 (0%)		1/87 (1.1%)
Nervous system disorders
Dizziness	0/86 (0%)		1/87 (1.1%)
Psychiatric disorders
Suicide attempt	1/86 (1.2%)		0/87 (0%)
Renal and urinary disorders
Proteinuria	1/86 (1.2%)		0/87 (0%)
Renal impairment	1/86 (1.2%)		0/87 (0%)
Skin and subcutaneous tissue disorders
Rash	1/86 (1.2%)		0/87 (0%)
Other (Not Including Serious) Adverse Events
	Deferasirox Dispersible Tablet (DFX-DT)		Deferasirox Film-coated Tablet (DFX-FCT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/86 (80.2%)		72/87 (82.8%)
Gastrointestinal disorders
Abdominal pain	23/86 (26.7%)		23/87 (26.4%)
Abdominal pain upper	6/86 (7%)		10/87 (11.5%)
Constipation	13/86 (15.1%)		7/87 (8%)
Diarrhoea	30/86 (34.9%)		27/87 (31%)
Dyspepsia	2/86 (2.3%)		6/87 (6.9%)
Nausea	23/86 (26.7%)		24/87 (27.6%)
Vomiting	18/86 (20.9%)		15/87 (17.2%)
General disorders
Asthenia	8/86 (9.3%)		4/87 (4.6%)
Fatigue	7/86 (8.1%)		5/87 (5.7%)
Pyrexia	7/86 (8.1%)		7/87 (8%)
Infections and infestations
Bacteriuria	5/86 (5.8%)		5/87 (5.7%)
Gastroenteritis	3/86 (3.5%)		5/87 (5.7%)
Influenza	5/86 (5.8%)		0/87 (0%)
Upper respiratory tract infection	6/86 (7%)		6/87 (6.9%)
Urinary tract infection	6/86 (7%)		3/87 (3.4%)
Investigations
Blood creatinine increased	7/86 (8.1%)		8/87 (9.2%)
Urine protein/creatinine ratio increased	11/86 (12.8%)		17/87 (19.5%)
Metabolism and nutrition disorders
Hyperphosphataemia	5/86 (5.8%)		4/87 (4.6%)
Musculoskeletal and connective tissue disorders
Back pain	5/86 (5.8%)		4/87 (4.6%)
Nervous system disorders
Headache	12/86 (14%)		5/87 (5.7%)
Renal and urinary disorders
Haematuria	2/86 (2.3%)		8/87 (9.2%)
Proteinuria	4/86 (4.7%)		8/87 (9.2%)
Pyuria	2/86 (2.3%)		6/87 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	4/86 (4.7%)		7/87 (8%)

Limitations/Caveats

[Not Specified]

More Information

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.