Trial Outcomes & Findings for Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet) (NCT NCT02125877)
NCT ID: NCT02125877
Last Updated: 2017-07-25
Results Overview
The percentage of participants with adverse events, serious adverse events and deaths was assessed.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
173 participants
Primary outcome timeframe
28 weeks
Results posted on
2017-07-25
Participant Flow
Participants were randomized in a 1:1 ratio.
Participant milestones
| Measure |
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.
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
86
|
87
|
|
Overall Study
Pharmacokinetic Analysis Set
|
83
|
83
|
|
Overall Study
Pharmacokinetic Subset A
|
16
|
15
|
|
Overall Study
Safety Set
|
86
|
87
|
|
Overall Study
COMPLETED
|
73
|
77
|
|
Overall Study
NOT COMPLETED
|
13
|
10
|
Reasons for withdrawal
| Measure |
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.
|
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
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Administrative problems
|
0
|
1
|
|
Overall Study
Participant/guardian decision
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Protocol deviation
|
4
|
1
|
|
Overall Study
Adverse Event
|
6
|
4
|
Baseline Characteristics
Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
Baseline characteristics by cohort
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
n=173 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35.1 Years
STANDARD_DEVIATION 18.60 • n=5 Participants
|
34.6 Years
STANDARD_DEVIATION 19.97 • n=7 Participants
|
34.9 Years
STANDARD_DEVIATION 19.25 • n=5 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
85 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 28 weeksPopulation: The safety set, which included all participants who received at least one dose of study drug, was analyzed.
The percentage of participants with adverse events, serious adverse events and deaths was assessed.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
|
|---|---|---|
|
Overall Safety as Measured by Frequency of Adverse Events
SAEs
|
15.1 Percentage of participants
|
18.4 Percentage of participants
|
|
Overall Safety as Measured by Frequency of Adverse Events
Deaths
|
0 Percentage of participants
|
1.1 Percentage of participants
|
|
Overall Safety as Measured by Frequency of Adverse Events
Adverse events
|
89.5 Percentage of participants
|
89.7 Percentage of participants
|
PRIMARY outcome
Timeframe: baseline (BL), 30 weeksPopulation: The safety set, which included all participants who received at least one dose of study drug, was analyzed.
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.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
|
|---|---|---|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
absolute neut., extended range: <0.5 x 10^9/L
|
4.7 Percentage of participants
|
0 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
serum creat, 2 cons >33% incr. from BL and >ULN
|
4.7 Percentage of participants
|
3.4 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
creat clearance, notable range: 2 cons <60mL/min
|
7.0 Percentage of participants
|
2.3 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
AST, extended range: >10 x ULN and >2 x BL
|
1.2 Percentage of participants
|
0 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
platelet count, notable range: <100 x 10^9/L
|
9.3 Percentage of participants
|
8.0 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
platelet count, extended range: <50 x 10^9/L
|
3.5 Percentage of participants
|
5.7 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
absolute neutrophils, notable range: <1.5 x 10^9/L
|
8.1 Percentage of participants
|
13.8 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
creat clearance, extended range: 2 cons <40mL/min
|
2.3 Percentage of participants
|
2.3 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
urin protein/urin creat ratio, 2 cons >1.0 mg/mg
|
2.3 Percentage of participants
|
0 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
ALT, notable range: >5 x ULN and >2 x BL
|
1.2 Percentage of participants
|
1.1 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
ALT, extended range: >10 x ULN and >2 x BL
|
1.2 Percentage of participants
|
0 Percentage of participants
|
|
Overall Safety as Measured by Changes in Laboratory Values From Baseline
AST, notable range: >5 x ULN and >2 x BL
|
0 Percentage of participants
|
1.1 Percentage of participants
|
SECONDARY outcome
Timeframe: 28 weeksPopulation: The safety set, which included all participants who received at least one dose of study drug, was analyzed.
The percentage of participants with any GI adverse event, diarrhea, constipation, nausea, vomiting, abdominal pain was assessed.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
|
|---|---|---|
|
Frequency of Selected Gastro-intestinal (GI) Adverse Events
Any GI adverse event
|
61.6 Percentage of participants
|
58.6 Percentage of participants
|
|
Frequency of Selected Gastro-intestinal (GI) Adverse Events
Abdominal pain
|
26.7 Percentage of participants
|
26.4 Percentage of participants
|
|
Frequency of Selected Gastro-intestinal (GI) Adverse Events
Constipation
|
15.1 Percentage of participants
|
8.0 Percentage of participants
|
|
Frequency of Selected Gastro-intestinal (GI) Adverse Events
Diarrhea
|
34.9 Percentage of participants
|
33.3 Percentage of participants
|
|
Frequency of Selected Gastro-intestinal (GI) Adverse Events
Nausea
|
26.7 Percentage of participants
|
27.6 Percentage of participants
|
|
Frequency of Selected Gastro-intestinal (GI) Adverse Events
Vomiting
|
22.1 Percentage of participants
|
17.2 Percentage of participants
|
SECONDARY outcome
Timeframe: weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)Population: 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.
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.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
|
|---|---|---|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 13, adherence (n=59,64)
|
11.2 score on a scale
Standard Deviation 3.56
|
7.8 score on a scale
Standard Deviation 2.05
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 13, concerns (n=59,64)
|
12.7 score on a scale
Standard Deviation 2.50
|
13.6 score on a scale
Standard Deviation 1.87
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 24, satisfaction/preference (n=63,60)
|
5.8 score on a scale
Standard Deviation 2.28
|
2.9 score on a scale
Standard Deviation 1.58
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 24, concerns (n=63,60)
|
11.8 score on a scale
Standard Deviation 3.07
|
13.7 score on a scale
Standard Deviation 1.84
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 24, adherence (n=63,60)
|
12.5 score on a scale
Standard Deviation 5.32
|
7.5 score on a scale
Standard Deviation 2.41
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 2, adherence (n=70,70)
|
10.3 score on a scale
Standard Deviation 3.80
|
7.6 score on a scale
Standard Deviation 2.14
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 2, satisfaction/preference (n=70,70)
|
5.2 score on a scale
Standard Deviation 2.24
|
2.8 score on a scale
Standard Deviation 1.37
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 2, concerns (n=70,70)
|
12.9 score on a scale
Standard Deviation 2.94
|
13.8 score on a scale
Standard Deviation 2.02
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 3, adherence (n=58,51)
|
10.9 score on a scale
Standard Deviation 4.09
|
7.7 score on a scale
Standard Deviation 2.06
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 3, satisfaction/preference (n=58,51)
|
5.4 score on a scale
Standard Deviation 2.22
|
2.6 score on a scale
Standard Deviation 1.05
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 3, concerns (n=58,51)
|
12.4 score on a scale
Standard Deviation 2.73
|
14.0 score on a scale
Standard Deviation 1.49
|
|
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
week 13, satisfaction/preference (n=59,64)
|
5.4 score on a scale
Standard Deviation 2.14
|
2.9 score on a scale
Standard Deviation 1.54
|
SECONDARY outcome
Timeframe: weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)Population: 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.
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.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
|
|---|---|---|
|
Palatability Questionnaire Score
week 3 (n=57,51)
|
8.8 score on a scale
Standard Deviation 3.01
|
10.8 score on a scale
Standard Deviation 0.45
|
|
Palatability Questionnaire Score
week 13 (n=59,62)
|
9.3 score on a scale
Standard Deviation 2.84
|
10.8 score on a scale
Standard Deviation 1.16
|
|
Palatability Questionnaire Score
week 24 (n=63,60)
|
8.8 score on a scale
Standard Deviation 3.10
|
10.9 score on a scale
Standard Deviation 0.34
|
|
Palatability Questionnaire Score
week 2 (n=69,70)
|
9.0 score on a scale
Standard Deviation 3.01
|
10.8 score on a scale
Standard Deviation 0.50
|
SECONDARY outcome
Timeframe: weeks -1, 4, 8, 12, 16, 20, 24Population: 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.
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.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
|
|---|---|---|
|
Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
week 8 (n=59,51)
|
1.4 score on a scale
Standard Deviation 2.45
|
1.1 score on a scale
Standard Deviation 2.16
|
|
Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
week 20 (n40,39)
|
1.5 score on a scale
Standard Deviation 3.27
|
0.9 score on a scale
Standard Deviation 1.44
|
|
Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
week -1 (n=69,65)
|
1.4 score on a scale
Standard Deviation 2.10
|
1.9 score on a scale
Standard Deviation 3.69
|
|
Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
week 4 (n=60,64)
|
1.8 score on a scale
Standard Deviation 3.49
|
1.1 score on a scale
Standard Deviation 2.15
|
|
Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
week 12 (n=51,45)
|
1.7 score on a scale
Standard Deviation 3.16
|
1.0 score on a scale
Standard Deviation 1.78
|
|
Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
week 16 (n=48,41)
|
1.9 score on a scale
Standard Deviation 3.75
|
0.9 score on a scale
Standard Deviation 1.92
|
|
Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
week 24 (n32,26)
|
1.5 score on a scale
Standard Deviation 3.29
|
1.2 score on a scale
Standard Deviation 1.89
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24Population: The safety set, which included all participants who received at least one dose of study drug, was analyzed.
A compliance questionnaire assessed whether the medication was taken. Weekly average compliance was calculated when there were at least four non-missing daily responses.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
|
|---|---|---|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 8
|
56 Participants
|
46 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 9
|
53 Participants
|
45 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 10
|
52 Participants
|
46 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 22
|
38 Participants
|
34 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 1
|
56 Participants
|
53 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 2
|
64 Participants
|
64 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 3
|
62 Participants
|
56 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 4
|
58 Participants
|
58 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 5
|
56 Participants
|
58 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 6
|
62 Participants
|
51 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 7
|
55 Participants
|
48 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 11
|
50 Participants
|
42 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 12
|
50 Participants
|
41 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 13
|
49 Participants
|
47 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 14
|
51 Participants
|
42 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 15
|
48 Participants
|
42 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 16
|
48 Participants
|
40 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 17
|
43 Participants
|
39 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 18
|
43 Participants
|
38 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 19
|
40 Participants
|
37 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 20
|
40 Participants
|
36 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 21
|
39 Participants
|
36 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 23
|
36 Participants
|
33 Participants
|
|
Number of Participants With Weekly Average Compliance of Medication Consumption
week 24
|
30 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: weeks 1, 4, 8, 12, 16, 20, 24Population: 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.
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.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 Participants
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
|
|---|---|---|
|
Weekly Dose Violation Rate
week 16 (n=48,40)
|
13.5 percent dose violation
Standard Deviation 31.08
|
10.0 percent dose violation
Standard Deviation 24.5
|
|
Weekly Dose Violation Rate
week 20 (n=40,36)
|
22.6 percent dose violation
Standard Deviation 38.38
|
11.3 percent dose violation
Standard Deviation 26.67
|
|
Weekly Dose Violation Rate
week 24 (n=30,24)
|
17.1 percent dose violation
Standard Deviation 34.26
|
10.1 percent dose violation
Standard Deviation 25.47
|
|
Weekly Dose Violation Rate
week 1 (n=56,53)
|
17.7 percent dose violation
Standard Deviation 31.04
|
15.8 percent dose violation
Standard Deviation 29.42
|
|
Weekly Dose Violation Rate
week 4 (n=58,58)
|
15.8 percent dose violation
Standard Deviation 32.51
|
6.7 percent dose violation
Standard Deviation 15.45
|
|
Weekly Dose Violation Rate
week 8 (n=56,46)
|
18.0 percent dose violation
Standard Deviation 35.38
|
8.4 percent dose violation
Standard Deviation 22.17
|
|
Weekly Dose Violation Rate
week 12 (n=50,41)
|
15.7 percent dose violation
Standard Deviation 34.22
|
10.7 percent dose violation
Standard Deviation 22.63
|
SECONDARY outcome
Timeframe: 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 dosePopulation: The Pharmacokinetic subset A analysis set was considered for the analysis, but only participants with non-missing values were analyzed.
Blood samples were collected to assess AUClast.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=16 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=15 Participants
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
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
week1 (n=14,15)
|
1110 umol/L*h
Standard Deviation 495
|
1040 umol/L*h
Standard Deviation 405
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
week 3 (n=13,15)
|
1590 umol/L*h
Standard Deviation 540
|
2110 umol/L*h
Standard Deviation 987
|
SECONDARY outcome
Timeframe: 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 dosePopulation: The Pharmacokinetic subset A analysis set was considered for the analysis, but only participants with non-missing values were analyzed
Blood samples were collected to assess Cmax.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=16 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=15 Participants
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
|
|---|---|---|
|
Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
week 1 (n=14,15)
|
74.6 umol/L
Standard Deviation 30.7
|
79.3 umol/L
Standard Deviation 23.5
|
|
Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
week 3 (n=14,15)
|
118 umol/L
Standard Deviation 82.3
|
139 umol/L
Standard Deviation 57.2
|
SECONDARY outcome
Timeframe: 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 dosePopulation: The Pharmacokinetic subset A analysis set was considered for the analysis, but only participants with non-missing values were analyzed
Blood samples were collected to assess Tmax.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=16 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=15 Participants
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
|
|---|---|---|
|
Time to Reach the Maximum Plasma Concentration After Drug Administration (Tmax)
week 1 (n=14,15)
|
3.57 hour
Interval 1.15 to 7.89
|
2.00 hour
Interval 1.15 to 15.6
|
|
Time to Reach the Maximum Plasma Concentration After Drug Administration (Tmax)
week 3 (n=14,15)
|
2.85 hour
Interval 1.4 to 8.39
|
2.02 hour
Interval 1.07 to 5.06
|
SECONDARY outcome
Timeframe: 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-dosePopulation: The Pharmacokinetic analysis set for all participants was considered for this analysis, but only participants with non-missing values were included in the analysis.
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.
Outcome measures
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=83 Participants
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=83 Participants
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
|
|---|---|---|
|
Dererasirox Plasma Concentration
week 21, 2 hours post-dose (n=59,64)
|
89.8 umol/L
Standard Deviation 59.3
|
105 umol/L
Standard Deviation 51.2
|
|
Dererasirox Plasma Concentration
week 3, pre-dose (n=63,70)
|
39.6 umol/L
Standard Deviation 48.4
|
27.3 umol/L
Standard Deviation 20.4
|
|
Dererasirox Plasma Concentration
week 3, 2 hours post-dose (n=67,76)
|
80.8 umol/L
Standard Deviation 52.2
|
95.5 umol/L
Standard Deviation 53.0
|
|
Dererasirox Plasma Concentration
week 13, pre-dose (n=69.56)
|
37.1 umol/L
Standard Deviation 37.8
|
31.3 umol/L
Standard Deviation 22.9
|
|
Dererasirox Plasma Concentration
week 13, 2 hours post-dose (n=74,59)
|
78.7 umol/L
Standard Deviation 39.5
|
92.5 umol/L
Standard Deviation 39.1
|
|
Dererasirox Plasma Concentration
week 21, pre-dose (n=54,59)
|
46.6 umol/L
Standard Deviation 46.4
|
43.1 umol/L
Standard Deviation 36.8
|
Adverse Events
Deferasirox Dispersible Tablet (DFX-DT)
Serious events: 13 serious events
Other events: 69 other events
Deaths: 0 deaths
Deferasirox Film-coated Tablet (DFX-FCT)
Serious events: 16 serious events
Other events: 72 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 participants at risk
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 participants at risk
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
|
|---|---|---|
|
Renal and urinary disorders
Renal impairment
|
1.2%
1/86
|
0.00%
0/87
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.2%
1/86
|
0.00%
0/87
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/86
|
1.1%
1/87
|
|
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia
|
1.2%
1/86
|
0.00%
0/87
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/86
|
1.1%
1/87
|
|
Blood and lymphatic system disorders
Haemolysis
|
1.2%
1/86
|
0.00%
0/87
|
|
Cardiac disorders
Atrial fibrillation
|
1.2%
1/86
|
0.00%
0/87
|
|
Cardiac disorders
Cardiac failure acute
|
1.2%
1/86
|
0.00%
0/87
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.2%
1/86
|
0.00%
0/87
|
|
Gastrointestinal disorders
Anal fissure
|
1.2%
1/86
|
0.00%
0/87
|
|
Gastrointestinal disorders
Ascites
|
1.2%
1/86
|
0.00%
0/87
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/86
|
2.3%
2/87
|
|
Gastrointestinal disorders
Dysphagia
|
1.2%
1/86
|
0.00%
0/87
|
|
Gastrointestinal disorders
Neutropenic colitis
|
0.00%
0/86
|
1.1%
1/87
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.2%
1/86
|
0.00%
0/87
|
|
Gastrointestinal disorders
Vomiting
|
1.2%
1/86
|
0.00%
0/87
|
|
General disorders
Face oedema
|
1.2%
1/86
|
0.00%
0/87
|
|
General disorders
Oedema
|
1.2%
1/86
|
0.00%
0/87
|
|
General disorders
Pyrexia
|
0.00%
0/86
|
1.1%
1/87
|
|
Hepatobiliary disorders
Biliary colic
|
0.00%
0/86
|
1.1%
1/87
|
|
Hepatobiliary disorders
Cholecystitis
|
1.2%
1/86
|
0.00%
0/87
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/86
|
1.1%
1/87
|
|
Infections and infestations
Appendicitis
|
1.2%
1/86
|
0.00%
0/87
|
|
Infections and infestations
Brucellosis
|
0.00%
0/86
|
1.1%
1/87
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/86
|
1.1%
1/87
|
|
Infections and infestations
Pneumonia
|
0.00%
0/86
|
1.1%
1/87
|
|
Infections and infestations
Post procedural pneumonia
|
1.2%
1/86
|
0.00%
0/87
|
|
Infections and infestations
Respiratory tract infection
|
1.2%
1/86
|
0.00%
0/87
|
|
Infections and infestations
Sepsis
|
0.00%
0/86
|
2.3%
2/87
|
|
Infections and infestations
Septic shock
|
0.00%
0/86
|
1.1%
1/87
|
|
Infections and infestations
Subcutaneous abscess
|
1.2%
1/86
|
0.00%
0/87
|
|
Infections and infestations
Viral infection
|
1.2%
1/86
|
0.00%
0/87
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/86
|
2.3%
2/87
|
|
Injury, poisoning and procedural complications
Delayed haemolytic transfusion reaction
|
1.2%
1/86
|
0.00%
0/87
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
1.2%
1/86
|
0.00%
0/87
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.00%
0/86
|
1.1%
1/87
|
|
Investigations
Ejection fraction decreased
|
1.2%
1/86
|
0.00%
0/87
|
|
Investigations
Urine protein/creatinine ratio increased
|
0.00%
0/86
|
1.1%
1/87
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.2%
1/86
|
0.00%
0/87
|
|
Metabolism and nutrition disorders
Dehydration
|
1.2%
1/86
|
0.00%
0/87
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/86
|
1.1%
1/87
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.2%
1/86
|
0.00%
0/87
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.00%
0/86
|
1.1%
1/87
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.2%
1/86
|
0.00%
0/87
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas
|
0.00%
0/86
|
1.1%
1/87
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia
|
0.00%
0/86
|
1.1%
1/87
|
|
Nervous system disorders
Dizziness
|
0.00%
0/86
|
1.1%
1/87
|
|
Psychiatric disorders
Suicide attempt
|
1.2%
1/86
|
0.00%
0/87
|
|
Renal and urinary disorders
Proteinuria
|
1.2%
1/86
|
0.00%
0/87
|
Other adverse events
| Measure |
Deferasirox Dispersible Tablet (DFX-DT)
n=86 participants at risk
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.
|
Deferasirox Film-coated Tablet (DFX-FCT)
n=87 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
26.7%
23/86
|
26.4%
23/87
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.0%
6/86
|
11.5%
10/87
|
|
Gastrointestinal disorders
Constipation
|
15.1%
13/86
|
8.0%
7/87
|
|
Gastrointestinal disorders
Diarrhoea
|
34.9%
30/86
|
31.0%
27/87
|
|
Gastrointestinal disorders
Dyspepsia
|
2.3%
2/86
|
6.9%
6/87
|
|
Gastrointestinal disorders
Nausea
|
26.7%
23/86
|
27.6%
24/87
|
|
Gastrointestinal disorders
Vomiting
|
20.9%
18/86
|
17.2%
15/87
|
|
General disorders
Asthenia
|
9.3%
8/86
|
4.6%
4/87
|
|
General disorders
Fatigue
|
8.1%
7/86
|
5.7%
5/87
|
|
General disorders
Pyrexia
|
8.1%
7/86
|
8.0%
7/87
|
|
Infections and infestations
Bacteriuria
|
5.8%
5/86
|
5.7%
5/87
|
|
Infections and infestations
Gastroenteritis
|
3.5%
3/86
|
5.7%
5/87
|
|
Infections and infestations
Influenza
|
5.8%
5/86
|
0.00%
0/87
|
|
Infections and infestations
Upper respiratory tract infection
|
7.0%
6/86
|
6.9%
6/87
|
|
Infections and infestations
Urinary tract infection
|
7.0%
6/86
|
3.4%
3/87
|
|
Investigations
Blood creatinine increased
|
8.1%
7/86
|
9.2%
8/87
|
|
Investigations
Urine protein/creatinine ratio increased
|
12.8%
11/86
|
19.5%
17/87
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
5.8%
5/86
|
4.6%
4/87
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.8%
5/86
|
4.6%
4/87
|
|
Nervous system disorders
Headache
|
14.0%
12/86
|
5.7%
5/87
|
|
Renal and urinary disorders
Haematuria
|
2.3%
2/86
|
9.2%
8/87
|
|
Renal and urinary disorders
Proteinuria
|
4.7%
4/86
|
9.2%
8/87
|
|
Renal and urinary disorders
Pyuria
|
2.3%
2/86
|
6.9%
6/87
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.7%
4/86
|
8.0%
7/87
|
Additional Information
Study Director
Novartis
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 or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER