- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02125877
Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
July 22, 2017 updated by: Novartis Pharmaceuticals
A Randomized, Open-label, Multicenter, Two Arm, Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
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
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
173
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Buenos aires, Argentina, C1221ADC
- Novartis Investigative Site
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Linz, Austria, A-4010
- Novartis Investigative Site
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Wien, Austria, 1140
- Novartis Investigative Site
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Lille cedex, France, 59020
- Novartis Investigative Site
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Paris, France, 75010
- Novartis Investigative Site
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Berlin, Germany, 13353
- Novartis Investigative Site
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Dresden, Germany, 01307
- Novartis Investigative Site
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Goslar, Germany, 38642
- Novartis Investigative Site
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Hannover, Germany, 30170
- Novartis Investigative Site
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Leipzig, Germany, 04103
- Novartis Investigative Site
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Potsdam, Germany, 14467
- Novartis Investigative Site
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Baden-Württemberg
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Mannheim, Baden-Württemberg, Germany, 68305
- Novartis Investigative Site
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GR
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Athens, GR, Greece, GR-115 27
- Novartis Investigative Site
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Patra - RIO, GR, Greece, 265 04
- Novartis Investigative Site
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Thessaloniki, GR, Greece, 546 42
- Novartis Investigative Site
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Napoli, Italy, 80138
- Novartis Investigative Site
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BR
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Brindisi, BR, Italy, 72100
- Novartis Investigative Site
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CT
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Catania, CT, Italy, 95125
- Novartis Investigative Site
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FE
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Cona, FE, Italy, 44100
- Novartis Investigative Site
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GE
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Genova, GE, Italy, 16132
- Novartis Investigative Site
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Genova, GE, Italy, 16128
- Novartis Investigative Site
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ITA
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Cagliari, ITA, Italy, 09121
- Novartis Investigative Site
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LE
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Lecce, LE, Italy, 73100
- Novartis Investigative Site
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MI
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Milano, MI, Italy, 20162
- Novartis Investigative Site
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Milano, MI, Italy, 20122
- Novartis Investigative Site
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PA
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Palermo, PA, Italy, 90127
- Novartis Investigative Site
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Palermo, PA, Italy, 90146
- Novartis Investigative Site
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RC
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Reggio Calabria, RC, Italy, 89100
- Novartis Investigative Site
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VR
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Verona, VR, Italy, 37126
- Novartis Investigative Site
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Beirut
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Hazmiyeh, Beirut, Lebanon, PO BOX 213
- Novartis Investigative Site
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Kuala Lumpur, Malaysia, 50589
- Novartis Investigative Site
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Pulau Pinang, Malaysia, 10990
- Novartis Investigative Site
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Distrito Federal
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Mexico, Distrito Federal, Mexico, 06726
- Novartis Investigative Site
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Russia
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Moskow, Russia, Russian Federation, 117198
- Novartis Investigative Site
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Dammam, Saudi Arabia, 15215
- Novartis Investigative Site
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Dammam, Saudi Arabia, 40145
- Novartis Investigative Site
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Jeddah, Saudi Arabia, 21589
- Novartis Investigative Site
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Riyadh, Saudi Arabia, 11472
- Novartis Investigative Site
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Barcelona, Spain, 08041
- Novartis Investigative Site
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Madrid, Spain, 28033
- Novartis Investigative Site
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Bangkok, Thailand, 10700
- Novartis Investigative Site
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Bangkok, Thailand, 10400
- Novartis Investigative Site
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Al Ain - Abu Dhabi, United Arab Emirates
- Novartis Investigative Site
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Dubai, United Arab Emirates, 9115
- Novartis Investigative Site
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London, United Kingdom, N19 5NF
- Novartis Investigative Site
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London, United Kingdom, NW1 2PJ
- Novartis Investigative Site
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California
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Orange, California, United States, 92868-3874
- Children's Hospital of Orange County Onc Dept
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Illinois
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Chicago, Illinois, United States, 60611
- Lurie Children's Hospital of Chicago Onc Dept
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Children's Hospital Boston Department of Hematology
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New York
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New York, New York, United States, 10021
- Weill Cornell Medical College-Cornell University Onc Dept
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104-4399
- Children's Hospital of Philadelphia Onc. Dept
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
10 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Key Inclusion Criteria:
- Male and female patients aged ≥ 10 years
- Patients with transfusion-dependent thalassemia and iron overload, requiring deferasirox DT at doses of ≥ 30 mg/kg/day as per the investigator's decision OR Patients with very low, low or intermediate (int) risk myelodysplastic syndrome (MDS) and iron overload, requiring deferasirox DT at doses of ≥ 20 mg/kg/day as per the investigator's decision.
- History of transfusion of at least 20 PRBC units and anticipated to be transfused with at least 8 units of PRBCs annually during the study
- Serum ferritin > 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).
Key Exclusion Criteria:
- Creatinine clearance below the contraindication limit in the locally approved prescribing information. Creatinine clearance will be estimated from serum creatinine at screening Visit 1 and screening Visit 2 and the mean value will be used for eligibility criteria.
- Serum creatinine > 1.5 xULN at screening measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).
- ALT (SGPT) > 5xULN, unless LIC confirmed as >10 mg Fe/dw within 6 months prior to screening visit 1.
- Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample at screening Visit 1 or screening Visit 2.
- Patients with significant impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Liver disease with severity of Child-Pugh Class B or C
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Deferasirox dispersible tablet (DFX-DT)
Iron chelation naïve participants received DFX-DT 20 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 5 to 10 mg/kg/day, with a maximum dose of 40 mg/kg/day.
Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose.
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Deferasirox DT was provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use.
Other Names:
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Experimental: Deferasirox film-coated tablet (DFX-FCT)
Participants received DFX-FCT 14 mg/kg/day once daily orally from weeks 1 - 4. After week 4, the dose could be adjusted by +/- 3.5 to 7 mg/kg/day, with a maximum dose of 28 mg/kg/day.
Iron chelation pre-treated participants were supposed to start on a dose that was equivalent to their pre-washout dose
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Deferasirox FCT was provided as 90 mg, 180 mg and 360 mg film-coated tablets for oral use.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Safety as Measured by Frequency of Adverse Events
Time Frame: 28 weeks
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The percentage of participants with adverse events, serious adverse events and deaths was assessed.
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28 weeks
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Overall Safety as Measured by Changes in Laboratory Values From Baseline
Time Frame: baseline (BL), 30 weeks
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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.
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baseline (BL), 30 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Frequency of Selected Gastro-intestinal (GI) Adverse Events
Time Frame: 28 weeks
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The percentage of participants with any GI adverse event, diarrhea, constipation, nausea, vomiting, abdominal pain was assessed.
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28 weeks
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Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
Time Frame: weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)
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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.
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weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)
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Palatability Questionnaire Score
Time Frame: weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)
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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.
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weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)
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Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
Time Frame: weeks -1, 4, 8, 12, 16, 20, 24
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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.
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weeks -1, 4, 8, 12, 16, 20, 24
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Number of Participants With Weekly Average Compliance of Medication Consumption
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
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A compliance questionnaire assessed whether the medication was taken.
Weekly average compliance was calculated when there were at least four non-missing daily responses.
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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
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Weekly Dose Violation Rate
Time Frame: weeks 1, 4, 8, 12, 16, 20, 24
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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.
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weeks 1, 4, 8, 12, 16, 20, 24
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Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (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
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Blood samples were collected to assess AUClast.
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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
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Observed Maximum Plasma Concentration Following Drug Administration (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
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Blood samples were collected to assess Cmax.
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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
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Time to Reach the Maximum Plasma Concentration After Drug Administration (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
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Blood samples were collected to assess Tmax.
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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
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Dererasirox Plasma Concentration
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
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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.
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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
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 8, 2014
Primary Completion (Actual)
February 24, 2016
Study Completion (Actual)
February 24, 2016
Study Registration Dates
First Submitted
April 26, 2014
First Submitted That Met QC Criteria
April 26, 2014
First Posted (Estimate)
April 29, 2014
Study Record Updates
Last Update Posted (Actual)
July 25, 2017
Last Update Submitted That Met QC Criteria
July 22, 2017
Last Verified
July 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CICL670F2201
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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