A Phase 2 interventional study of Deferasirox dispersible tablet and Defearisox film-coated tablet in Chronic Iron Overload Due to Transfusion-dependant Anemias, sponsored by Novartis Pharmaceuticals. Completed at 51 sites in 16 countries. Open to participants aged 10 Years and older. Per ClinicalTrials.gov, last updated 2017-07-25.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2, Interventional, and Treatment
Assessed the new film-coated tablet formulation to the currently approved dispersible tablet formulation with regards to overall safety, Gastrointestinal (GI) tolerability, palatability, satisfaction and compliance
168 studies on the registry are indexed under Iron Overload; 8 are open to participants now.
This study's enrollment of 173 is above the median of 60 across 108 interventional studies indexed under Iron Overload.
Browse Iron Overload studies →Novartis Pharmaceuticals is the lead sponsor of 2,711 studies on the registry; 218 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 435 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.
Drug: Deferasirox dispersible tablet
Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day. Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
Drug: Defearisox film-coated tablet
Deferasirox DT was provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use.
Also known as: ICL670, DT (dispersible tablet)
Deferasirox FCT was provided as 90 mg, 180 mg and 360 mg film-coated tablets for oral use.
Also known as: ICL670, FCT (film-coated tablet)
Overall Safety as Measured by Frequency of Adverse Events
The percentage of participants with adverse events, serious adverse events and deaths was assessed.
Time frame: 28 weeks
Overall Safety as Measured by Changes in Laboratory Values From Baseline
The percentage of participants with post-baseline laboratory values meeting specified criteria for notable/extended range was assessed. The following laboratory parameters were measured: platelet count, absolute neutrophils, serum creatinine , creatinine clearance, urinary protein/urinary creatinine ratio, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Note that within data categories, creat = creatinine, cons = consecutive, ULN = upper limit of normal and urin = urinary.
Time frame: baseline (BL), 30 weeks
Frequency of Selected Gastro-intestinal (GI) Adverse Events
The percentage of participants with any GI adverse event, diarrhea, constipation, nausea, vomiting, abdominal pain was assessed.
Time frame: 28 weeks
Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
The modified SICT consisted of 13 items that represent 3 domains: adherence, satisfaction and concerns. The adherence domain consisted of 7 items, 6 which were measured using a 5-point response scale and was calculated by summing the 6 items. The score range from 6 to 30 and higher scores indicated worse adherence. The satisfaction domain consisted of 3 items, 2 which were measured using a 5-point response scale and was calculated by summing the 2 items. The score range from 2 to 10 and higher scores indicated worse satisfaction. The concerns domain consisted of 3 items to address any concerns or worries with his/her medication. All 3 items were measured on a 5-point response scale and were calculated by summing the 3 items. The score range from 3 to 15 and higher scores indicated fewer concerns. For all three domains, the meaningful difference between two treatment arms was determined to be 1 point.
Time frame: weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)
Palatability Questionnaire Score
The palatability questionnaire consisted of 4 items. The first item measured the taste and aftertaste of the medication and were scored a on a 5-point response scale. The second item offered an additional response option of "no aftertaste". The last 2 items referred to whether the medication was taken, i.e. swallowed or vomited, and how the participant perceived the amount of medication to be taken. The palatability summary score was calculated using a scoring matrix from items 1, 3 and 4 scores and the score ranges from 0 - 11. Higher scores indicated the best palatability. A meaningful difference between two treatment arms was determined to be 1 point.
Time frame: weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)
Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
The GI symptom diary consisted of 6 items, five which were scored using a 0 - 10 rating scale with item appropriate anchors to rate the symptom, for example, Pain in your belly: 0 = no pain and 10 = worst pain. The GI diary summary score was created using the 10 point response scale for the 5 items. The GI symptom daily diary had a minimum score of 0 and a maximum score of 50. The weekly average score for the 7 days was calculated for each individual item and the GI summary score was created from these weekly averages. Higher scores indicated worse symptoms. A meaningful difference between two treatment arms was determined to be 0.3 point.
Time frame: weeks -1, 4, 8, 12, 16, 20, 24
Number of Participants With Weekly Average Compliance of Medication Consumption
A compliance questionnaire assessed whether the medication was taken. Weekly average compliance was calculated when there were at least four non-missing daily responses.
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Weekly Dose Violation Rate
The dose violation is defined as a dose either missed completely or not taken in accordance with the timing instruction (no later than 12:00 pm. The rate was calculated as \[number of dose violations/drug exposure (days)\] x 100.
Time frame: weeks 1, 4, 8, 12, 16, 20, 24
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Blood samples were collected to assess AUClast.
Time frame: week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose
Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
Blood samples were collected to assess Cmax.
Time frame: week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose
Time to Reach the Maximum Plasma Concentration After Drug Administration (Tmax)
Blood samples were collected to assess Tmax.
Time frame: week 1, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose; week 3, day 1: pre-dose (0 hour) and 1, 2, 3, 4, 8 and 24 hours post dose
Dererasirox Plasma Concentration
Blood samples were collected to assess deferasirox concentration. Dose-adjusted calculations are presented: (concentration/actual dose)\*20 for participants on DFX-DT and (concentration/actual dose)\*14 for participants on DFX-FCT.
Time frame: Week 3, day 1, pre-dose (0 hour (h)) and 2 h post-dose; week 13, day 1, pre-dose (0 hour (h)) and 2 h post-dose; and week 21, day 1, pre-dose (0 hour (h)) and 2 h post-dose
| Milestone | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| Started | 86 | 87 |
| Pharmacokinetic analysis set | 83 | 83 |
| Pharmacokinetic subset a | 16 | 15 |
| Safety set | 86 | 87 |
| Completed | 73 | 77 |
| Not completed | 13 | 10 |
| Withdrew: Physician decision | 1 | 0 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Administrative problems | 0 | 1 |
| Withdrew: Participant/guardian decision | 0 | 2 |
| Withdrew: Withdrawal by subject | 2 | 1 |
| Withdrew: Protocol deviation | 4 | 1 |
| Withdrew: Adverse event | 6 | 4 |
The percentage of participants with adverse events, serious adverse events and deaths was assessed.
| Percentage of participants | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| Adverse events | 89.5 | 89.7 |
| SAEs | 15.1 | 18.4 |
| Deaths | 0 | 1.1 |
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.
| Percentage of participants | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| platelet count, notable range: <100 x 10^9/L | 9.3 | 8.0 |
| platelet count, extended range: <50 x 10^9/L | 3.5 | 5.7 |
| absolute neutrophils, notable range: <1.5 x 10^9/L | 8.1 | 13.8 |
| absolute neut., extended range: <0.5 x 10^9/L | 4.7 | 0 |
| serum creat, 2 cons >33% incr. from BL and >ULN | 4.7 | 3.4 |
| creat clearance, notable range: 2 cons <60mL/min | 7.0 | 2.3 |
| creat clearance, extended range: 2 cons <40mL/min | 2.3 | 2.3 |
| urin protein/urin creat ratio, 2 cons >1.0 mg/mg | 2.3 | 0 |
| ALT, notable range: >5 x ULN and >2 x BL | 1.2 | 1.1 |
| ALT, extended range: >10 x ULN and >2 x BL | 1.2 | 0 |
| AST, notable range: >5 x ULN and >2 x BL | 0 | 1.1 |
| AST, extended range: >10 x ULN and >2 x BL | 1.2 | 0 |
The percentage of participants with any GI adverse event, diarrhea, constipation, nausea, vomiting, abdominal pain was assessed.
| Percentage of participants | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| Any GI adverse event | 61.6 | 58.6 |
| Abdominal pain | 26.7 | 26.4 |
| Constipation | 15.1 | 8.0 |
| Diarrhea | 34.9 | 33.3 |
| Nausea | 26.7 | 27.6 |
| Vomiting | 22.1 | 17.2 |
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.
| score on a scale | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week 2, adherence (n=70,70) | 10.3 ± 3.80 | 7.6 ± 2.14 |
| week 2, satisfaction/preference (n=70,70) | 5.2 ± 2.24 | 2.8 ± 1.37 |
| week 2, concerns (n=70,70) | 12.9 ± 2.94 | 13.8 ± 2.02 |
| week 3, adherence (n=58,51) | 10.9 ± 4.09 | 7.7 ± 2.06 |
| week 3, satisfaction/preference (n=58,51) | 5.4 ± 2.22 | 2.6 ± 1.05 |
| week 3, concerns (n=58,51) | 12.4 ± 2.73 | 14.0 ± 1.49 |
| week 13, adherence (n=59,64) | 11.2 ± 3.56 | 7.8 ± 2.05 |
| week 13, satisfaction/preference (n=59,64) | 5.4 ± 2.14 | 2.9 ± 1.54 |
| week 13, concerns (n=59,64) | 12.7 ± 2.50 | 13.6 ± 1.87 |
| week 24, adherence (n=63,60) | 12.5 ± 5.32 | 7.5 ± 2.41 |
| week 24, satisfaction/preference (n=63,60) | 5.8 ± 2.28 | 2.9 ± 1.58 |
| week 24, concerns (n=63,60) | 11.8 ± 3.07 | 13.7 ± 1.84 |
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.
| score on a scale | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week 2 (n=69,70) | 9.0 ± 3.01 | 10.8 ± 0.50 |
| week 3 (n=57,51) | 8.8 ± 3.01 | 10.8 ± 0.45 |
| week 13 (n=59,62) | 9.3 ± 2.84 | 10.8 ± 1.16 |
| week 24 (n=63,60) | 8.8 ± 3.10 | 10.9 ± 0.34 |
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.
| score on a scale | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week -1 (n=69,65) | 1.4 ± 2.10 | 1.9 ± 3.69 |
| week 4 (n=60,64) | 1.8 ± 3.49 | 1.1 ± 2.15 |
| week 8 (n=59,51) | 1.4 ± 2.45 | 1.1 ± 2.16 |
| week 12 (n=51,45) | 1.7 ± 3.16 | 1.0 ± 1.78 |
| week 16 (n=48,41) | 1.9 ± 3.75 | 0.9 ± 1.92 |
| week 20 (n40,39) | 1.5 ± 3.27 | 0.9 ± 1.44 |
| week 24 (n32,26) | 1.5 ± 3.29 | 1.2 ± 1.89 |
A compliance questionnaire assessed whether the medication was taken. Weekly average compliance was calculated when there were at least four non-missing daily responses.
| Participants | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week 1 | 56 | 53 |
| week 2 | 64 | 64 |
| week 3 | 62 | 56 |
| week 4 | 58 | 58 |
| week 5 | 56 | 58 |
| week 6 | 62 | 51 |
| week 7 | 55 | 48 |
| week 8 | 56 | 46 |
| week 9 | 53 | 45 |
| week 10 | 52 | 46 |
| week 11 | 50 | 42 |
| week 12 | 50 | 41 |
| week 13 | 49 | 47 |
| week 14 | 51 | 42 |
| week 15 | 48 | 42 |
| week 16 | 48 | 40 |
| week 17 | 43 | 39 |
| week 18 | 43 | 38 |
| week 19 | 40 | 37 |
| week 20 | 40 | 36 |
| week 21 | 39 | 36 |
| week 22 | 38 | 34 |
| week 23 | 36 | 33 |
| week 24 | 30 | 24 |
The dose violation is defined as a dose either missed completely or not taken in accordance with the timing instruction (no later than 12:00 pm. The rate was calculated as \[number of dose violations/drug exposure (days)\] x 100.
| percent dose violation | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week 1 (n=56,53) | 17.7 ± 31.04 | 15.8 ± 29.42 |
| week 4 (n=58,58) | 15.8 ± 32.51 | 6.7 ± 15.45 |
| week 8 (n=56,46) | 18.0 ± 35.38 | 8.4 ± 22.17 |
| week 12 (n=50,41) | 15.7 ± 34.22 | 10.7 ± 22.63 |
| week 16 (n=48,40) | 13.5 ± 31.08 | 10.0 ± 24.5 |
| week 20 (n=40,36) | 22.6 ± 38.38 | 11.3 ± 26.67 |
| week 24 (n=30,24) | 17.1 ± 34.26 | 10.1 ± 25.47 |
Blood samples were collected to assess AUClast.
| umol/L*h | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week1 (n=14,15) | 1110 ± 495 | 1040 ± 405 |
| week 3 (n=13,15) | 1590 ± 540 | 2110 ± 987 |
Blood samples were collected to assess Cmax.
| umol/L | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week 1 (n=14,15) | 74.6 ± 30.7 | 79.3 ± 23.5 |
| week 3 (n=14,15) | 118 ± 82.3 | 139 ± 57.2 |
Blood samples were collected to assess Tmax.
| hour | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week 1 (n=14,15) | 3.57 (1.15 to 7.89) | 2.00 (1.15 to 15.6) |
| week 3 (n=14,15) | 2.85 (1.40 to 8.39) | 2.02 (1.07 to 5.06) |
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.
| umol/L | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| week 3, pre-dose (n=63,70) | 39.6 ± 48.4 | 27.3 ± 20.4 |
| week 3, 2 hours post-dose (n=67,76) | 80.8 ± 52.2 | 95.5 ± 53.0 |
| week 13, pre-dose (n=69.56) | 37.1 ± 37.8 | 31.3 ± 22.9 |
| week 13, 2 hours post-dose (n=74,59) | 78.7 ± 39.5 | 92.5 ± 39.1 |
| week 21, pre-dose (n=54,59) | 46.6 ± 46.4 | 43.1 ± 36.8 |
| week 21, 2 hours post-dose (n=59,64) | 89.8 ± 59.3 | 105 ± 51.2 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Deferasirox Dispersible Tablet (DFX-DT) | — | 13/86 (15.1%) | 69/86 (80.2%) |
| Deferasirox Film-coated Tablet (DFX-FCT) | — | 16/87 (18.4%) | 72/87 (82.8%) |
| Event | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 0/86 | 2/87 |
| SepsisInfections and infestations | 0/86 | 2/87 |
| Accidental overdoseInjury, poisoning and procedural complications | 0/86 | 2/87 |
| Autoimmune haemolytic anaemiaBlood and lymphatic system disorders | 1/86 | 0/87 |
| HaemolysisBlood and lymphatic system disorders | 1/86 | 0/87 |
| Atrial fibrillationCardiac disorders | 1/86 | 0/87 |
| Cardiac failure acuteCardiac disorders | 1/86 | 0/87 |
| Abdominal pain upperGastrointestinal disorders | 1/86 | 0/87 |
| Anal fissureGastrointestinal disorders | 1/86 | 0/87 |
| AscitesGastrointestinal disorders | 1/86 | 0/87 |
| Event | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 30/86 | 27/87 |
| NauseaGastrointestinal disorders | 23/86 | 24/87 |
| Abdominal painGastrointestinal disorders | 23/86 | 23/87 |
| VomitingGastrointestinal disorders | 18/86 | 15/87 |
| Urine protein/creatinine ratio increasedInvestigations | 11/86 | 17/87 |
| ConstipationGastrointestinal disorders | 13/86 | 7/87 |
| HeadacheNervous system disorders | 12/86 | 5/87 |
| Abdominal pain upperGastrointestinal disorders | 6/86 | 10/87 |
| AstheniaGeneral disorders | 8/86 | 4/87 |
| Blood creatinine increasedInvestigations | 7/86 | 8/87 |
| Age, Continuous(Years) | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) | Total |
|---|---|---|---|
| Mean | 35.1 ± 18.60 | 34.6 ± 19.97 | 34.9 ± 19.25 |
| Sex: Female, Male(Participants) | Deferasirox Dispersible Tablet (DFX-DT) | Deferasirox Film-coated Tablet (DFX-FCT) | Total |
|---|---|---|---|
| Female | 47 | 41 | 88 |
| Male | 39 | 46 | 85 |
Ran from Jul 2014 to primary completion in Feb 2016, 19 months.
Results were first posted in Oct 2016, 7 months after primary completion.
Of 14 phase 2 interventional studies under Iron Overload, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 45. This study's 19 months is below that.
How these figures are worked out, and which studies are left out of them.
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