Chronic Iron Overload Due to Transfusion-dependant Anemias Clinical Trial
Official title:
A Randomized, Open-label, Multicenter, Two Arm, Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
| Verified date | July 2017 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Completed |
| Enrollment | 173 |
| Est. completion date | February 24, 2016 |
| Est. primary completion date | February 24, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 10 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Novartis Investigative Site | Buenos aires | |
| Austria | Novartis Investigative Site | Linz | |
| Austria | Novartis Investigative Site | Wien | |
| France | Novartis Investigative Site | Lille cedex | |
| France | Novartis Investigative Site | Paris | |
| Germany | Novartis Investigative Site | Berlin | |
| Germany | Novartis Investigative Site | Dresden | |
| Germany | Novartis Investigative Site | Goslar | |
| Germany | Novartis Investigative Site | Hannover | |
| Germany | Novartis Investigative Site | Leipzig | |
| Germany | Novartis Investigative Site | Mannheim | Baden-Württemberg |
| Germany | Novartis Investigative Site | Potsdam | |
| Greece | Novartis Investigative Site | Athens | GR |
| Greece | Novartis Investigative Site | Patra - RIO | GR |
| Greece | Novartis Investigative Site | Thessaloniki | GR |
| Italy | Novartis Investigative Site | Brindisi | BR |
| Italy | Novartis Investigative Site | Cagliari | ITA |
| Italy | Novartis Investigative Site | Catania | CT |
| Italy | Novartis Investigative Site | Cona | FE |
| Italy | Novartis Investigative Site | Genova | GE |
| Italy | Novartis Investigative Site | Genova | GE |
| Italy | Novartis Investigative Site | Lecce | LE |
| Italy | Novartis Investigative Site | Milano | MI |
| Italy | Novartis Investigative Site | Milano | MI |
| Italy | Novartis Investigative Site | Napoli | |
| Italy | Novartis Investigative Site | Palermo | PA |
| Italy | Novartis Investigative Site | Palermo | PA |
| Italy | Novartis Investigative Site | Reggio Calabria | RC |
| Italy | Novartis Investigative Site | Verona | VR |
| Lebanon | Novartis Investigative Site | Hazmiyeh | Beirut |
| Malaysia | Novartis Investigative Site | Kuala Lumpur | |
| Malaysia | Novartis Investigative Site | Pulau Pinang | |
| Mexico | Novartis Investigative Site | Mexico | Distrito Federal |
| Russian Federation | Novartis Investigative Site | Moskow | Russia |
| Saudi Arabia | Novartis Investigative Site | Dammam | |
| Saudi Arabia | Novartis Investigative Site | Dammam | |
| Saudi Arabia | Novartis Investigative Site | Jeddah | |
| Saudi Arabia | Novartis Investigative Site | Riyadh | |
| Spain | Novartis Investigative Site | Barcelona | |
| Spain | Novartis Investigative Site | Madrid | |
| Thailand | Novartis Investigative Site | Bangkok | |
| Thailand | Novartis Investigative Site | Bangkok | |
| United Arab Emirates | Novartis Investigative Site | Al Ain - Abu Dhabi | |
| United Arab Emirates | Novartis Investigative Site | Dubai | |
| United Kingdom | Novartis Investigative Site | London | |
| United Kingdom | Novartis Investigative Site | London | |
| United States | Children's Hospital Boston Department of Hematology | Boston | Massachusetts |
| United States | Lurie Children's Hospital of Chicago Onc Dept | Chicago | Illinois |
| United States | Weill Cornell Medical College-Cornell University Onc Dept | New York | New York |
| United States | Children's Hospital of Orange County Onc Dept | Orange | California |
| United States | Children's Hospital of Philadelphia Onc. Dept | Philadelphia | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Argentina, Austria, France, Germany, Greece, Italy, Lebanon, Malaysia, Mexico, Russian Federation, Saudi Arabia, Spain, Thailand, United Arab Emirates, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall Safety as Measured by Frequency of Adverse Events | The percentage of participants with adverse events, serious adverse events and deaths was assessed. | 28 weeks | |
| Primary | 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. | baseline (BL), 30 weeks | |
| Secondary | 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. | 28 weeks | |
| Secondary | 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. | weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose) | |
| Secondary | 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. | weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose) | |
| Secondary | 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. | weeks -1, 4, 8, 12, 16, 20, 24 | |
| Secondary | 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. | 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 | |
| Secondary | 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. | weeks 1, 4, 8, 12, 16, 20, 24 | |
| Secondary | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | Blood samples were collected to assess AUClast. | 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 | |
| Secondary | Observed Maximum Plasma Concentration Following Drug Administration (Cmax) | Blood samples were collected to assess Cmax. | 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 | |
| Secondary | Time to Reach the Maximum Plasma Concentration After Drug Administration (Tmax) | Blood samples were collected to assess Tmax. | 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 | |
| Secondary | 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. | 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 |