A Randomized, Open-label, Multicenter, Two Arm, Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film-coated Tablet)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 173
- 试验地点
- 6
- 主要终点
- Overall Safety as Measured by Frequency of Adverse Events
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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
- •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
- •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
研究组 & 干预措施
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
干预措施: Defearisox film-coated tablet (Drug)
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.
干预措施: Deferasirox dispersible tablet (Drug)
结局指标
主要结局
Overall Safety as Measured by Frequency of Adverse Events
时间窗: 28 weeks
The percentage of participants with adverse events, serious adverse events and deaths was assessed.
Overall Safety as Measured by Changes in Laboratory Values From Baseline
时间窗: baseline (BL), 30 weeks
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.
次要结局
- Frequency of Selected Gastro-intestinal (GI) Adverse Events(28 weeks)
- Observed Maximum Plasma Concentration Following Drug Administration (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)
- Dererasirox Plasma Concentration(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)
- Weekly Dose Violation Rate(weeks 1, 4, 8, 12, 16, 20, 24)
- Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (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)
- Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT)(weeks 2, 3, 13 and 24 (end of treatment or within 7 days of last dose))
- Palatability Questionnaire Score(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(weeks -1, 4, 8, 12, 16, 20, 24)
- Number of Participants With Weekly Average Compliance of Medication Consumption(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)
- Time to Reach the Maximum Plasma Concentration After Drug Administration (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)