Trial Outcomes & Findings for Efficacy and Safety of Deferasirox in Non-transfusion Dependent Thalassemia Patients With Iron Overload and a One Year Open-label Extension Study (NCT NCT00873041)
NCT ID: NCT00873041
Last Updated: 2013-07-09
Results Overview
LIC was measured by magnetic resonance imaging technique at baseline and Week 52. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 52 with treatment as factor and baseline LIC as covariate.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
166 participants
Primary outcome timeframe
Baseline, Week 52
Results posted on
2013-07-09
Participant Flow
There was a 4 week screening period to determine eligibility prior to randomization.
Participant milestones
| Measure |
5 mg/kg/Day Deferasirox
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
10 mg/kg/Day Deferasirox
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
Placebo/Deferasirox
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
|---|---|---|---|
|
Core Study
STARTED
|
55
|
55
|
56
|
|
Core Study
COMPLETED
|
48
|
49
|
51
|
|
Core Study
NOT COMPLETED
|
7
|
6
|
5
|
|
Extension Study
STARTED
|
41
|
44
|
48
|
|
Extension Study
COMPLETED
|
40
|
44
|
46
|
|
Extension Study
NOT COMPLETED
|
1
|
0
|
2
|
Reasons for withdrawal
| Measure |
5 mg/kg/Day Deferasirox
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
10 mg/kg/Day Deferasirox
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
Placebo/Deferasirox
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
|---|---|---|---|
|
Core Study
Adverse Event
|
2
|
3
|
1
|
|
Core Study
Withdrawal by Subject
|
1
|
2
|
2
|
|
Core Study
Lost to Follow-up
|
3
|
1
|
0
|
|
Core Study
Abnormal laboratory value
|
0
|
0
|
1
|
|
Core Study
Protocol deviation
|
1
|
0
|
1
|
|
Extension Study
Adverse Event
|
1
|
0
|
1
|
|
Extension Study
Administrative reasons
|
0
|
0
|
1
|
Baseline Characteristics
Efficacy and Safety of Deferasirox in Non-transfusion Dependent Thalassemia Patients With Iron Overload and a One Year Open-label Extension Study
Baseline characteristics by cohort
| Measure |
5 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
10 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
Placebo
n=56 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. Participants received a starting dose of 5 or 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Total
n=166 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
<18 years
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Age, Customized
Between 18 and 65 years
|
49 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
144 Participants
n=4 Participants
|
|
Age, Customized
>=65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
77 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
89 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 52Population: Full Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 52. Only patients with both baseline and at least one post-baseline value were included for this analysis.
LIC was measured by magnetic resonance imaging technique at baseline and Week 52. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 52 with treatment as factor and baseline LIC as covariate.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=51 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=54 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=54 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52
|
-1.95 mg iron (Fe)/g dry weight (dw)
Standard Error 0.500
|
-3.80 mg iron (Fe)/g dry weight (dw)
Standard Error 0.484
|
0.38 mg iron (Fe)/g dry weight (dw)
Standard Error 0.486
|
PRIMARY outcome
Timeframe: Core Baseline to End of Extension Study (up to 24 months)Population: Full Analysis consisted of all randomized participants. Patients with post-baseline LIC satisfying criterion at any time during the study are counted as responder. Patients with no baseline LIC or without any post-baseline LIC measurements will be assumed as non-responder.
Liver iron concentration was measured at Core Baseline and at the end of the Extension Study. Magnetic Resonance Imaging (MRI) scans were analyzed at a central laboratory to determine the LIC value. The percentage of participants with LIC \< 5 mgFe/g dw (milligram iron/gram dry weight) change from Baseline at the end of the Extension Study is reported.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=110 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=56 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study
|
39.1 Percentage of participants
Interval 30.5 to 48.4
|
37.5 Percentage of participants
Interval 26.0 to 56.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Full Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 24. Only patients with both baseline and at least one post-baseline value were included for this analysis.
LIC was measured by magnetic resonance imaging technique at baseline and Week 24. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 24 with treatment as factor and baseline LIC as covariate.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=49 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=48 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=51 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24
|
-0.87 mg iron (Fe)/g dry weight (dw)
Standard Error 0.448
|
-0.90 mg iron (Fe)/g dry weight (dw)
Standard Error 0.450
|
-0.24 mg iron (Fe)/g dry weight (dw)
Standard Error 0.439
|
SECONDARY outcome
Timeframe: Baseline, (Day 286 to End of Study [Day 365])Population: Full Analysis set (all randomized patients). Only participants with both baseline and post-baseline values are included in analyses. If serum ferritin was missing during the fourth quarter, the last available average of serum ferritin per quarter was used for the calculation of the change from baseline.
Baseline serum ferritin average was the average of all available ferritin values from screening to last sample prior to the first intake of study drug. Fourth quarter serum ferritin average was the average of all serum ferritin values obtained within days 286- End of Study. Change from baseline: fourth quarter serum ferritin average - baseline serum ferritin average.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=51 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=50 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=53 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter
|
-130.47 μg/L
Standard Deviation 260.555
|
-249.16 μg/L
Standard Deviation 389.356
|
128.63 μg/L
Standard Deviation 249.689
|
SECONDARY outcome
Timeframe: Baseline, (Day 106 to Day 195)Population: Full Analysis set (all randomized patients). Only participants with both baseline and post-baseline values are included in analyses. If serum ferritin was missing during the second quarter, the last available average of serum ferritin per quarter was used for the calculation of the change from baseline.
Baseline serum ferritin average was the average of all available ferritin values from screening to last sample prior to the first intake of study drug. Second quarter serum ferritin average was the average of all serum ferritin values obtained within days 106-195. Change from baseline: second quarter serum ferritin average - baseline serum ferritin average.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=52 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=54 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=56 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Change in Serum Ferritin Between Baseline and Second Quarter
|
8.20 μg/L
Standard Deviation 244.443
|
-17.75 μg/L
Standard Deviation 368.812
|
106.45 μg/L
Standard Deviation 330.217
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: Safety Analysis Set included all randomized participants who received treatment.
Percentage of Participants with Mild, Moderate and Severe adverse events (AE) any primary system organ class regardless of study drug relationship. A patient with multiple occurrences of an AE is counted only once in the AE category for that treatment. A patient with multiple severity ratings for an AE while on a treatment is only counted once under the maximum rating.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=56 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe
Moderate
|
27.3 Percentage of participants
|
16.4 Percentage of participants
|
21.4 Percentage of participants
|
|
Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe
Mild
|
36.4 Percentage of participants
|
43.6 Percentage of participants
|
42.9 Percentage of participants
|
|
Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe
Severe
|
12.7 Percentage of participants
|
18.2 Percentage of participants
|
16.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24, Week 52Population: Full Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 24 and Week 52. Only patients with dose increases after week 24, with both baseline and at least one post-baseline value were included for this analysis.
LIC was measured by magnetic resonance imaging technique at baseline, Week 24 and Week 52. Dose Doubling (Dose Increases) began at Week 24.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=26 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=25 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=30 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24
Change from baseline at Week 24 (n=26,24,30)
|
0.56 mg iron (Fe)/g dry weight (dw)
Standard Deviation 2.992
|
0.69 mg iron (Fe)/g dry weight (dw)
Standard Deviation 3.131
|
0.94 mg iron (Fe)/g dry weight (dw)
Standard Deviation 2.693
|
|
Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24
Change from baseline at Week 52
|
-1.82 mg iron (Fe)/g dry weight (dw)
Standard Deviation 3.101
|
-4.02 mg iron (Fe)/g dry weight (dw)
Standard Deviation 4.849
|
0.62 mg iron (Fe)/g dry weight (dw)
Standard Deviation 4.128
|
SECONDARY outcome
Timeframe: Baseline, 52 weeksPopulation: Participants from the Full Analysis Set (all randomized participants).
The correlation between serum ferritin and LIC was investigated using a scatter plot with a regression line for the following cases: * Baseline serum ferritin versus baseline LIC * Serum ferritin difference from baseline at fourth quarter versus difference from baseline in LIC at Week 52. A value of 1.0 indicates a perfect correlation.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=165 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
Baseline
|
0.653 Correlation coefficient
|
—
|
—
|
|
Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
Week 52 (n=134)
|
0.609 Correlation coefficient
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: Full Analysis Set (all randomized participants). Only patients with a value both at baseline and at considered timepoint are included in analyses.
Blood was collected for Hemoglobin at baseline and Month 12. Change from baseline= Month 12 hemoglobin - baseline hemoglobin.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=47 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=48 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=49 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Change From Baseline in Hemoglobin at Month 12
|
-1.8 g/L
Standard Deviation 5.45
|
-0.7 g/L
Standard Deviation 6.27
|
-2.8 g/L
Standard Deviation 7.31
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: Full Analysis Set (all randomized patients). Only patients with a value both at baseline and at considered timepoint are included in the analyses.
Blood was collected for transferrin saturation at Baseline and Month 12. Change from baseline= Month 12 transferrin saturation - baseline transferrin saturation.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=47 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=47 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=47 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Change From Baseline in Transferrin Saturation at Month 12
|
-3.79 Percent saturation
Standard Deviation 14.234
|
-3.64 Percent saturation
Standard Deviation 22.443
|
3.37 Percent saturation
Standard Deviation 10.083
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: Safety Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 52. Only patients with both baseline and at least one post-baseline value were included for this analysis.
LIC was measured by magnetic resonance imaging technique at baseline and Week 52. The change in liver iron concentration for participants in the placebo arm was used to assess the iron accumulation rate.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=54 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Change in Liver Iron Concentration (LIC) in Placebo Patients From Baseline to Week 52
|
0.26 mg iron (Fe)/g dry weight (dw)
Standard Deviation 3.501
|
—
|
—
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: Safety Set included all randomized participants who received treatment.
The percentage of participants with notable laboratory results: Platelet count: (\<100 x 10\^9/L) Absolute neutrophils: (\<1.5 x 10\^9/L) Alanine aminotransferase (ALT): (\>5 x Upper limit normal (ULN) and \>2 x baseline). Aspartate aminotransferase (AST): (\>5 x ULN and \>2 x baseline) Serum creatinine: (\>33% increase from baseline and \>ULN at ≥2 consecutive post-baseline values) Creatinine clearance: (\<60 mL/min at ≥2 consecutive post-baseline values) Urinary protein/creatinine ratio: (≥ 1.0 mg/mg at ≥2 consecutive post-baseline values)
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=56 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
Serum creatinine
|
0 Percentage of participants
|
5.5 Percentage of participants
|
0 Percentage of participants
|
|
Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
Creatinine clearance
|
1.8 Percentage of participants
|
1.8 Percentage of participants
|
0 Percentage of participants
|
|
Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
Urinary protein/creatinine ratio
|
1.8 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
Platelet count
|
5.5 Percentage of participants
|
5.5 Percentage of participants
|
10.7 Percentage of participants
|
|
Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
Absolute neutrophils
|
5.5 Percentage of participants
|
3.6 Percentage of participants
|
5.4 Percentage of participants
|
|
Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
ALT
|
0 Percentage of participants
|
0 Percentage of participants
|
1.8 Percentage of participants
|
|
Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
AST
|
0 Percentage of participants
|
1.8 Percentage of participants
|
1.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 52 WeeksPopulation: Safety Set includes all randomized participants who received treatment.
Systolic blood pressure was measured at each visit after the patient rested in the sitting position for at least 3 minutes. A Notably Abnormal Systolic Blood Pressure was defined as a measurement in one of the following two categories: High: ≥180 with an increase from baseline ≥20 mmHg Low: ≤90 with a decrease from baseline ≥20 mmHg
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=56 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure
High
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
1.8 Percentage of participants
|
|
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure
Low
|
10.9 Percentage of participants
|
5.5 Percentage of participants
|
16.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 52 WeeksPopulation: Safety Set includes all randomized participants who received treatment.
Diastolic blood pressure was measured at each visit after the patient rested in the sitting position for at least 3 minutes. A Notably Abnormal Diastolic Blood Pressure was defined as a measurement in one of the following two categories: High: ≥105 with an increase from baseline ≥15 mmHg Low: ≤50 with a decrease from baseline ≥15 mmHg
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=56 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure
High
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
|
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure
Low
|
14.5 Percentage of participants
|
10.9 Percentage of participants
|
14.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 52 WeeksPopulation: Safety Set includes all randomized participants who received treatment.
Pulse Rate was measured at each visit. A Notably Abnormal Pulse Rate was defined as a measurement in one of the following two categories: High: ≥120 with an increase from baseline ≥15 beats per minute (bpm) Low: ≤50 with a decrease from baseline ≥15 bpm
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=55 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
n=56 Participants
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate
High
|
1.8 Percentage of participants
|
0.0 Percentage of participants
|
3.6 Percentage of participants
|
|
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate
Low
|
0.0 Percentage of participants
|
1.8 Percentage of participants
|
0.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Core Baseline, Eighth Quarter (last 3 months of the study)Population: Full Analysis Set included all randomized participants. Only patients with a value both at baseline and at considered time point are included.
Blood was collected for serum ferritin at Core Baseline and monthly during the Eighth quarter of the Extension Study. Absolute change from Baseline: quarterly average - baseline average. A negative change from baseline indicated improvement.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=84 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=46 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter
|
-565.9 micrograms/liter
Standard Deviation 504.25
|
-504.3 micrograms/liter
Standard Deviation 770.60
|
—
|
SECONDARY outcome
Timeframe: Core Baseline, Month 24Population: Full Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 52. Only patients with both baseline and at least one post-baseline value were included for this analysis.
LIC was measured by magnetic resonance imaging technique at Baseline and Month 24. A negative change from baseline indicated improvement.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=84 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=46 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
|
-7.1 mg iron (Fe)/g dry weight (dw)
Standard Deviation 5.3
|
-6.7 mg iron (Fe)/g dry weight (dw)
Standard Deviation 6.67
|
—
|
SECONDARY outcome
Timeframe: Core Baseline, Month 24Population: Participants from the Extension Full Analysis Set (all randomized participants)in the Extension Study with data available for analysis.
The correlation between serum ferritin and LIC was investigated using a scatter plot with a regression line for serum ferritin difference from Baseline at Month 24 versus LIC difference from Baseline at Month 24. A value of 1.0 indicates a perfect correlation.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=129 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Extension Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
|
0.735 Correlation coefficient
|
—
|
—
|
SECONDARY outcome
Timeframe: Core Baseline, Month 24Population: Full Analysis Set (all randomized participants). Only patients with a value both at baseline and at considered timepoint are included in analyses.
Blood was collected for Hemoglobin at Baseline and Month 24. Change from Baseline= Month 24 hemoglobin - Baseline hemoglobin.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=59 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=29 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Extension Study: Change From Baseline in Hemoglobin at Month 24
|
-2.6 g/L
95% Confidence Interval 6.07 • Interval -4.19 to -1.03
|
-3.1 g/L
95% Confidence Interval 9.48 • Interval -6.73 to 0.48
|
—
|
SECONDARY outcome
Timeframe: Core Baseline, Month 24Population: Full Analysis Set (all randomized patients). Only patients with a value both at baseline and at considered timepoint are included in the analyses.
Blood was collected for transferrin saturation at Baseline and Month 24. Change from baseline= Month 24 transferrin saturation - baseline transferrin saturation.
Outcome measures
| Measure |
5 mg/kg/Day Deferasirox
n=66 Participants
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
10 mg/kg/Day Deferasirox
n=33 Participants
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Placebo
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
|---|---|---|---|
|
Extension Study: Change From Baseline in Transferrin Saturation at Month 24
|
-5.01 Percent saturation
95% Confidence Interval 24.36 • Interval -11.0 to 0.98
|
1.35 Percent saturation
95% Confidence Interval 13.01 • Interval -3.26 to 5.97
|
—
|
Adverse Events
Deferasirox 5 mg/kg/Day
Serious events: 11 serious events
Other events: 37 other events
Deaths: 0 deaths
Deferasirox 10 mg/kg/Day
Serious events: 12 serious events
Other events: 45 other events
Deaths: 0 deaths
Placebo/Deferasirox Any Dose
Serious events: 16 serious events
Other events: 48 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Deferasirox 5 mg/kg/Day
n=55 participants at risk
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
Deferasirox 10 mg/kg/Day
n=55 participants at risk
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
Placebo/Deferasirox Any Dose
n=56 participants at risk
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.8%
1/55
|
3.6%
2/55
|
5.4%
3/56
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Congenital, familial and genetic disorders
Atrial septal defect
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Eye disorders
Cataract
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Gastrointestinal disorders
Abdominal pain
|
1.8%
1/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Gastrointestinal disorders
Abdominal tenderness
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Gastrointestinal disorders
Food poisoning
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/55
|
3.6%
2/55
|
0.00%
0/56
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
General disorders
Pyrexia
|
1.8%
1/55
|
5.5%
3/55
|
1.8%
1/56
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/55
|
1.8%
1/55
|
1.8%
1/56
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/55
|
1.8%
1/55
|
1.8%
1/56
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Hepatobiliary disorders
Hepatotoxicity
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Infections and infestations
Babesiosis
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Infections and infestations
Cellulitis
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Infections and infestations
Dengue fever
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Infections and infestations
Gastroenteritis
|
5.5%
3/55
|
7.3%
4/55
|
3.6%
2/56
|
|
Infections and infestations
Helicobacter gastritis
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Infections and infestations
Influenza
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Infections and infestations
Liver abscess
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Infections and infestations
Pneumonia
|
0.00%
0/55
|
0.00%
0/55
|
3.6%
2/56
|
|
Infections and infestations
Respiratory tract infection
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Investigations
C-reactive protein
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Investigations
Weight decreased
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Nervous system disorders
Optic neuritis
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Nervous system disorders
Syncope
|
1.8%
1/55
|
0.00%
0/55
|
0.00%
0/56
|
|
Reproductive system and breast disorders
Ovarian cyst ruptured
|
0.00%
0/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/55
|
1.8%
1/55
|
0.00%
0/56
|
Other adverse events
| Measure |
Deferasirox 5 mg/kg/Day
n=55 participants at risk
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
Deferasirox 10 mg/kg/Day
n=55 participants at risk
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
Placebo/Deferasirox Any Dose
n=56 participants at risk
Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.9%
6/55
|
7.3%
4/55
|
5.4%
3/56
|
|
Eye disorders
Conjunctivitis
|
5.5%
3/55
|
1.8%
1/55
|
1.8%
1/56
|
|
Gastrointestinal disorders
Abdominal pain
|
7.3%
4/55
|
7.3%
4/55
|
16.1%
9/56
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.3%
4/55
|
16.4%
9/55
|
12.5%
7/56
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/55
|
0.00%
0/55
|
5.4%
3/56
|
|
Gastrointestinal disorders
Diarrhoea
|
14.5%
8/55
|
12.7%
7/55
|
21.4%
12/56
|
|
Gastrointestinal disorders
Dyspepsia
|
1.8%
1/55
|
5.5%
3/55
|
3.6%
2/56
|
|
Gastrointestinal disorders
Food poisoning
|
0.00%
0/55
|
5.5%
3/55
|
7.1%
4/56
|
|
Gastrointestinal disorders
Gastritis
|
5.5%
3/55
|
1.8%
1/55
|
3.6%
2/56
|
|
Gastrointestinal disorders
Nausea
|
9.1%
5/55
|
16.4%
9/55
|
21.4%
12/56
|
|
Gastrointestinal disorders
Tooth disorder
|
0.00%
0/55
|
0.00%
0/55
|
5.4%
3/56
|
|
Gastrointestinal disorders
Vomiting
|
7.3%
4/55
|
5.5%
3/55
|
14.3%
8/56
|
|
General disorders
Asthenia
|
3.6%
2/55
|
1.8%
1/55
|
5.4%
3/56
|
|
General disorders
Fatigue
|
5.5%
3/55
|
12.7%
7/55
|
10.7%
6/56
|
|
General disorders
Oedema peripheral
|
1.8%
1/55
|
1.8%
1/55
|
7.1%
4/56
|
|
General disorders
Pain
|
5.5%
3/55
|
0.00%
0/55
|
1.8%
1/56
|
|
General disorders
Pyrexia
|
18.2%
10/55
|
9.1%
5/55
|
26.8%
15/56
|
|
Infections and infestations
Gastroenteritis
|
5.5%
3/55
|
9.1%
5/55
|
7.1%
4/56
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/55
|
5.5%
3/55
|
3.6%
2/56
|
|
Infections and infestations
Influenza
|
7.3%
4/55
|
10.9%
6/55
|
8.9%
5/56
|
|
Infections and infestations
Nasopharyngitis
|
10.9%
6/55
|
9.1%
5/55
|
10.7%
6/56
|
|
Infections and infestations
Pharyngitis
|
10.9%
6/55
|
3.6%
2/55
|
3.6%
2/56
|
|
Infections and infestations
Rhinitis
|
3.6%
2/55
|
9.1%
5/55
|
5.4%
3/56
|
|
Infections and infestations
Tonsillitis
|
9.1%
5/55
|
5.5%
3/55
|
8.9%
5/56
|
|
Infections and infestations
Upper respiratory tract infection
|
16.4%
9/55
|
25.5%
14/55
|
25.0%
14/56
|
|
Infections and infestations
Viral infection
|
3.6%
2/55
|
0.00%
0/55
|
7.1%
4/56
|
|
Investigations
Blood creatinine increased
|
1.8%
1/55
|
5.5%
3/55
|
3.6%
2/56
|
|
Investigations
Heart rate increased
|
0.00%
0/55
|
0.00%
0/55
|
5.4%
3/56
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.5%
3/55
|
1.8%
1/55
|
5.4%
3/56
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.5%
3/55
|
3.6%
2/55
|
8.9%
5/56
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.6%
2/55
|
1.8%
1/55
|
10.7%
6/56
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
1.8%
1/55
|
0.00%
0/55
|
5.4%
3/56
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.6%
2/55
|
3.6%
2/55
|
5.4%
3/56
|
|
Nervous system disorders
Dizziness
|
7.3%
4/55
|
0.00%
0/55
|
1.8%
1/56
|
|
Nervous system disorders
Headache
|
5.5%
3/55
|
20.0%
11/55
|
21.4%
12/56
|
|
Psychiatric disorders
Insomnia
|
1.8%
1/55
|
5.5%
3/55
|
7.1%
4/56
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.5%
3/55
|
7.3%
4/55
|
14.3%
8/56
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.8%
1/55
|
1.8%
1/55
|
5.4%
3/56
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.5%
3/55
|
1.8%
1/55
|
0.00%
0/56
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.3%
4/55
|
12.7%
7/55
|
5.4%
3/56
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.5%
3/55
|
10.9%
6/55
|
8.9%
5/56
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER