Clinical trial NCT02125877: Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
Official title: A Randomized, Open-label, Multicenter, Two Arm, Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Iron Overload Due to Transfusion-dependant Anemias
Keywords: Iron overload
Chelation
Thalassemia
Myelodysplastic syndrome (MDS)
Transfusional hemisiderosis
Deferasirox
ICL670
Dispersible tablet
Film-coated tablet
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-04-29
Enrollment: 173
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Overall Safety as Measured by Frequency of Adverse Events
timeFrame: 28 weeks
measure: Overall Safety as Measured by Changes in Laboratory Values From Baseline
timeFrame: baseline (BL), 30 weeks
Secondary outcomes:
measure: Frequency of Selected Gastro-intestinal (GI) Adverse Events
timeFrame: 28 weeks
measure: Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)
timeFrame: weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)
measure: Palatability Questionnaire Score
timeFrame: weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose)
measure: Weekly Average of Daily Scores of the Gastrointestinal (GI) Symptom Diary
timeFrame: weeks -1, 4, 8, 12, 16, 20, 24
measure: Number of Participants With Weekly Average Compliance of Medication Consumption
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, 24
measure: Weekly Dose Violation Rate
timeFrame: weeks 1, 4, 8, 12, 16, 20, 24
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
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 dose
measure: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
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 dose
measure: Time to Reach the Maximum Plasma Concentration After Drug Administration (Tmax)
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 dose
measure: Dererasirox Plasma Concentration
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-dose
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County Onc Dept
state: California
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago Onc Dept
state: Illinois
city: Boston
country: United States
facility: Children's Hospital Boston Department of Hematology
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell Medical College-Cornell University Onc Dept
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia Onc. Dept
state: Pennsylvania
city: Buenos aires
country: Argentina
facility: Novartis Investigative Site
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Lille cedex
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
state: Baden-Württemberg
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Goslar
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Patra - RIO
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Brindisi
country: Italy
facility: Novartis Investigative Site
state: BR
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Cagliari
country: Italy
facility: Novartis Investigative Site
state: ITA
city: Lecce
country: Italy
facility: Novartis Investigative Site
state: LE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Reggio Calabria
country: Italy
facility: Novartis Investigative Site
state: RC
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Hazmiyeh
country: Lebanon
facility: Novartis Investigative Site
state: Beirut
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Pulau Pinang
country: Malaysia
facility: Novartis Investigative Site
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Moskow
country: Russian Federation
facility: Novartis Investigative Site
state: Russia
city: Dammam
country: Saudi Arabia
facility: Novartis Investigative Site
city: Dammam
country: Saudi Arabia
facility: Novartis Investigative Site
city: Jeddah
country: Saudi Arabia
facility: Novartis Investigative Site
city: Riyadh
country: Saudi Arabia
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Al Ain - Abu Dhabi
country: United Arab Emirates
facility: Novartis Investigative Site
city: Dubai
country: United Arab Emirates
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Taher AT, Origa R, Perrotta S, Kouraklis A, Ruffo GB, Kattamis A, Goh AS, Huang V, Zia A, Herranz RM, Porter JB. Patient-reported outcomes from a randomized phase II study of the deferasirox film-coated tablet in patients with transfusion-dependent anemias. Health Qual Life Outcomes. 2018 Nov 19;16(1):216. doi: 10.1186/s12955-018-1041-5.