Prospective, Multi-center, Single-arm, Open-label Long-term Study Assessing the Safety, Tolerability, and Effectiveness of Macitentan in Fontan-palliated Adult and Adolescent Subjects
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 112
- 试验地点
- 19
- 主要终点
- Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment
研究概览
简要总结
The aim of this open-label (OL) trial is to study the long-term use of macitentan for up to 2 years in Fontan-palliated adult and adolescent patients beyond the 52 weeks of treatment in the parent RUBATO double-blind (DB) study (AC-055H301, NCT03153137). This OL trial studies the long-term effect of macitentan in Fontan-palliated patients as it is not known if the effect of macitentan is sustained beyond 52 weeks (end of the parent RUBATO DB study). In addition, the trial also studies the long-term safety of macitentan as this is also unknown. Furthermore, the opportunity will be given to patients who were on placebo in the parent RUBATO DB study to receive macitentan 10 mg and benefit from a potentially active treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent/assent from the subject and/or a legal representative prior to initiation of any study-mandated procedures.
- •Subjects who have completed Week 52 of the parent AC-055H301/RUBATO DB study (NCT03153137)
- •Women of childbearing potential must:
- •have a negative serum pregnancy test prior to first intake of OL study drug, and,
- •agree to perform monthly pregnancy tests up to the end of the safety follow up (S-FU) period, and,
- •use reliable methods of contraception from enrollment up to at least 30 days after study treatment discontinuation.
排除标准
- •Clinical worsening leading to medical interventions including reoperation of Fontan circulation (Fontan take-down) during the enrollment period
- •Systolic blood pressure < 90 mmHg (< 85 mmHg for subjects < 18 years old and < 150 cm of height) at rest
- •Criteria related to macitentan use
- •Any known factor or disease that may interfere with treatment compliance or full participation in the study
研究组 & 干预措施
Open-label treatment period
oral administration of 10 mg macitentan once daily
干预措施: macitentan 10 mg (Drug)
结局指标
主要结局
Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment
时间窗: Up to 133 weeks
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.
Change From Baseline in Hemoglobin Over Time
时间窗: Baseline up to Week 130
Change from baseline in hemoglobin over time was reported in this outcome measure.
Change From Baseline in Prothrombin Time Over Time
时间窗: Baseline up to Week 130
Change from baseline in prothrombin time over time was reported in this outcome measure.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 133 weeks
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.
Number of Participants With Treatment-emergent Serious AEs (TESAEs)
时间窗: Up to 133 weeks
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be TESAEs.
Number of Participants With TEAEs Leading to Death
时间窗: Up to 133 weeks
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
时间窗: Up to 133 weeks
Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin \[gram/Liter {g/L}\], Platelets \[giga/L {10\^9 cells/L}\], Leukocytes \[10\^9 cells/L\], Lymphocytes \[10\^9 cells/L\], Neutrophils \[10\^9 cells/L\], Prothrombin International Normalized Ratio \[PINR;Ratio\], Aspartate Aminotransferase \[Units/L {U/L}\], Bilirubin \[micromoles/L {mcmol/L}\], Alkaline Phosphatase \[U/L\], Glomerular Filtration Rate \[milliliter/minute/1.73 meter square\], Glucose \[millimoles/L {mmol/L}\], Potassium \[mmol/L\], Sodium \[mmol/L\], Triglycerides \[mmol/L\] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Marked laboratory abnormalities reported for at least 1 participant were reported in this outcome measure. \>=:greater than or equal to; \>:greater than; \<:less than; ULN: upper limit of normal; L:Low, H:High, LLL:lower/worse than LL, HHH:higher/worse than HH.
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
时间窗: Baseline up to Week 130
Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
时间窗: Baseline up to Week 130
Change from baseline in ALT, AST, AP, and GGT over time were reported in this outcome measure.
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
时间窗: Baseline up to Week 130
Change from baseline in GFR over time was reported in this outcome measure.
Change From Baseline in Hematocrit Over Time
时间窗: Baseline up to Week 130
Change from baseline in hematocrit over time was reported in this outcome measure.
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
时间窗: Baseline up to Week 130
Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.
Change From Baseline in Pulse Rate Over Time
时间窗: Baseline up to Week 130
Change from baseline in pulse rate over time was reported in this outcome measure.
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
时间窗: Baseline up to Week 130
Change from baseline in SpO2 over time was reported in this outcome measure.
Change From Baseline in Body Weight Over Time
时间窗: Baseline up to Week 130
Change from baseline in body weight over time was reported in this outcome measure.
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
时间窗: Baseline up to Week 130
Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.
Change From Baseline in Prothrombin International Normalized Ratio Over Time
时间窗: Baseline up to Week 130
Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.
次要结局
- Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)(Baseline, Week 52, and Week 104)
- Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)(Baseline, Week 26, Week 52, Week 78, and Week 104)