- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT02125877
Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
22. juli 2017 oppdatert av: 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
Studieoversikt
Status
Fullført
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
173
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Buenos aires, Argentina, C1221ADC
- Novartis Investigative Site
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Al Ain - Abu Dhabi, De forente arabiske emirater
- Novartis Investigative Site
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Dubai, De forente arabiske emirater, 9115
- Novartis Investigative Site
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Russia
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Moskow, Russia, Den russiske føderasjonen, 117198
- Novartis Investigative Site
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California
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Orange, California, Forente stater, 92868-3874
- Children's Hospital of Orange County Onc Dept
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Illinois
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Chicago, Illinois, Forente stater, 60611
- Lurie Children's Hospital of Chicago Onc Dept
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Massachusetts
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Boston, Massachusetts, Forente stater, 02115
- Children's Hospital Boston Department of Hematology
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New York
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New York, New York, Forente stater, 10021
- Weill Cornell Medical College-Cornell University Onc Dept
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19104-4399
- Children's Hospital of Philadelphia Onc. Dept
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Lille cedex, Frankrike, 59020
- Novartis Investigative Site
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Paris, Frankrike, 75010
- Novartis Investigative Site
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GR
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Athens, GR, Hellas, GR-115 27
- Novartis Investigative Site
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Patra - RIO, GR, Hellas, 265 04
- Novartis Investigative Site
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Thessaloniki, GR, Hellas, 546 42
- Novartis Investigative Site
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Napoli, Italia, 80138
- Novartis Investigative Site
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BR
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Brindisi, BR, Italia, 72100
- Novartis Investigative Site
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CT
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Catania, CT, Italia, 95125
- Novartis Investigative Site
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FE
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Cona, FE, Italia, 44100
- Novartis Investigative Site
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GE
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Genova, GE, Italia, 16132
- Novartis Investigative Site
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Genova, GE, Italia, 16128
- Novartis Investigative Site
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ITA
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Cagliari, ITA, Italia, 09121
- Novartis Investigative Site
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LE
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Lecce, LE, Italia, 73100
- Novartis Investigative Site
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MI
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Milano, MI, Italia, 20162
- Novartis Investigative Site
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Milano, MI, Italia, 20122
- Novartis Investigative Site
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PA
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Palermo, PA, Italia, 90127
- Novartis Investigative Site
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Palermo, PA, Italia, 90146
- Novartis Investigative Site
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RC
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Reggio Calabria, RC, Italia, 89100
- Novartis Investigative Site
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VR
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Verona, VR, Italia, 37126
- Novartis Investigative Site
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Beirut
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Hazmiyeh, Beirut, Libanon, 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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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, Spania, 08041
- Novartis Investigative Site
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Madrid, Spania, 28033
- Novartis Investigative Site
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London, Storbritannia, N19 5NF
- Novartis Investigative Site
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London, Storbritannia, NW1 2PJ
- 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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Berlin, Tyskland, 13353
- Novartis Investigative Site
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Dresden, Tyskland, 01307
- Novartis Investigative Site
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Goslar, Tyskland, 38642
- Novartis Investigative Site
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Hannover, Tyskland, 30170
- Novartis Investigative Site
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Leipzig, Tyskland, 04103
- Novartis Investigative Site
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Potsdam, Tyskland, 14467
- Novartis Investigative Site
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Baden-Württemberg
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Mannheim, Baden-Württemberg, Tyskland, 68305
- Novartis Investigative Site
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Linz, Østerrike, A-4010
- Novartis Investigative Site
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Wien, Østerrike, 1140
- Novartis Investigative Site
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
10 år og eldre (Barn, Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Aktiv komparator: 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.
Andre navn:
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Eksperimentell: 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.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Overall Safety as Measured by Frequency of Adverse Events
Tidsramme: 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
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Frequency of Selected Gastro-intestinal (GI) Adverse Events
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
8. juli 2014
Primær fullføring (Faktiske)
24. februar 2016
Studiet fullført (Faktiske)
24. februar 2016
Datoer for studieregistrering
Først innsendt
26. april 2014
Først innsendt som oppfylte QC-kriteriene
26. april 2014
Først lagt ut (Anslag)
29. april 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
25. juli 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
22. juli 2017
Sist bekreftet
1. juli 2017
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- CICL670F2201
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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