Randomised Double Blind, Controlled, Parallel Group, Multicentre Study of a Subcutaneous Formulation of Icatibant Versus Oral Tranexamic Acid for the Treatment of Hereditary Angioedema (HAE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Time to Onset of Symptom Relief.
研究概览
简要总结
Primary Outcome Measures:
The primary endpoint was the time to onset of symptom relief of the first attack in the double blind phase. H0: λ icatibant/λ tranexamic acid =1 versus H1: λ icatibant/λ tranexamic acid ≠1 Where: λ icatibant refers to the hazard rate under icatibant and λ tranexamic acid refers to the hazard rate under tranexamic acid.
Secondary Outcome Measures:
- Additional efficacy assessments (Time to Almost Complete Symptom Relief)
- Safety and tolerability
- Pharmacoeconomics
详细描述
This was a Phase III, randomised, double blind, double dummy, multicentre, controlled,parallel group study of a 30 mg s.c. formulation of icatibant for the treatment of patients with moderate to very severe symptoms of cutaneous and/or abdominal symptoms of HAE.
The study consisted of two parts: controlled phase and OLE phase. For the primary endpoint, Efficacy was determined by evaluating the differences in study outcomes using a Visual Analogue Scale for patients treated with icatibant and tranexamic acid.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age above 18 years;
- •Documented diagnosis of HAE Type I or II (confirmed C1-INH deficiency);
- •Current edema in the cutaneous, abdominal and/or laryngeal areas;
- •Current edema moderate to severe according to the investigator's Symptom Score.
排除标准
- •Diagnosis of angioedema other than HAE,
- •Participation in a clinical trial of another investigational medicinal product (IMP)within the past month
- •Treatment with any pain medication since onset of the current angioedema attack
- •Treatment with replacement therapy, including C1-INH products, less than 3 days before onset of the current angioedema attack
- •Treatment with Tranexamic acid replacement therapy within a week before onset of the current angioedema attack
- •Treatment with ACE inhibitors
- •Contraindications for Tranexamic acid
- •Evidence of coronary artery disease based on medical history or Screening examination in particular unstable angina pectoris or severe coronary heart disease
- •Congestive heart failure (class 3 and 4)
- •Serum creatinine level of ≥ 250 μmol/L
- •Serious concomitant illness that the investigator considered to be a contraindication for participation in the trial
- •Pregnancy (as assessed prior to treatment) and/or breast-feeding
研究组 & 干预措施
Randomized controlled -Icatibant
Subjects received S.C icatibant+ oral placebo
Icatibant Form: solution for injection, 3 mL, 10 mg/mL Single dose: 30 mg (3 mL)
Placebo Form: hard capsule Single dose: 2 capsules Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart
干预措施: Icatibant (Drug)
Randomized controlled -Icatibant
Subjects received S.C icatibant+ oral placebo
Icatibant Form: solution for injection, 3 mL, 10 mg/mL Single dose: 30 mg (3 mL)
Placebo Form: hard capsule Single dose: 2 capsules Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart
干预措施: Oral Placebo (Drug)
Randomized controlled-Tranexamic acid
Subjects received oral Tranexamic acid+ S.C. placebo
Tranexamic acid Form: over encapsulated film tablet Single dose: 1000 mg (2 capsules) Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart
Placebo Form: solution for injection, matched to icatibant for injection Single dose: 3 mL Frequency: one subcutaneous injection in the abdominal region
干预措施: Tranexamic Acid (Drug)
Randomized controlled-Tranexamic acid
Subjects received oral Tranexamic acid+ S.C. placebo
Tranexamic acid Form: over encapsulated film tablet Single dose: 1000 mg (2 capsules) Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart
Placebo Form: solution for injection, matched to icatibant for injection Single dose: 3 mL Frequency: one subcutaneous injection in the abdominal region
干预措施: S.C. Placebo (Drug)
Controlled Open-label / laryngeal attack
Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.
干预措施: Icatibant (Drug)
Untreated patients at the baseline
Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing were treated in the open label phase with icatibant
干预措施: Icatibant (Drug)
结局指标
主要结局
Time to Onset of Symptom Relief.
时间窗: 2 days
The primary efficacy endpoint was Time to onset of symptom relief (TOSR) following treatment with either icatibant or tranexamic acid. The median time to onset of symptom relief for the icatibant group was compared to the the median time to onset of symptom relief for the tranexamic acid group. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the three primary symptoms: cutaneous swelling, cutaneous skin, and abdominal pain. The primary symptom was based on the type of attack. For abdominal attacks, the single primary symptom was abdominal pain. For cutaneous attacks, the single primary symptom was either skin swelling or skin pain, whichever was most severe.
次要结局
- Time to Almost Complete Symptom Relief(48 hours)