Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study Evaluating the Safety & Efficacy of Icatibant as a Treatment for Angiotensin-Converting Enzyme Inhibitor (ACE-I)-Induced Angioedema in Adults
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 118
- 试验地点
- 54
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
This study is being conducted to compare the safety and efficacy of icatibant with placebo in the treatment for Angiotensin-Converting Enzyme Inhibitor (ACE-I)-Induced Angioedema in Adults.
详细描述
Angiotensin-converting enzyme inhibitors (ACE-Is) are the class of medications prescribed most frequently for the treatment of hypertension. They are also used post myocardial infarction as well as in patients with heart failure, diabetes mellitus, and chronic kidney disease. Approximately 35 to 40 million patients are on ACE-Is worldwide.
Study HGT-FIR-096 is a multicenter, Phase III, randomized, double-blind, two-armed, placebo-controlled trial. The study population will consist of 118 adult patients, 18 years of age or older, who present with an acute ACE-I-induced angioedema attack. The primary aim of the study is to demonstrate that icatibant is significantly more effective than placebo in resolving attacks of angioedema caused by ACE-I based on the Time to Meeting Discharge Criteria (TMDC). Safety and tolerability, as well as the pharmacokinetics (PK), of icatibant will also be evaluated. Eligible patients will be randomized at a 1:1 ratio to receive a single sub-cutaneous injection of either 30 mg icatibant or placebo.
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, Outcomes Assessor)
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
- •Male or female, 18 years of age or older.
- •Patient is currently being treated with an ACE inhibitor.
- •Patient presenting with an ACE inhibitor-induced angioedema attack of the head and/or neck region within 12 hours of onset (must be sufficiently less than 12 hours to allow study drug to be given with 12 hours of attack onset).
- •Angioedema must be considered at least moderate in severity for at least one of the four angioedema-associated airway symptoms (difficulty breathing, difficulty swallowing, voice changes, tongue swelling).
- •Patient must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient.
- •Females must have a negative urine pregnancy test prior to administration of the study medication, with the exception of those females who have had a total hysterectomy or bilateral oophorectomy, or who are 2 years post-menopausal.
排除标准
- •Patient has a diagnosis of angioedema of other etiology (eg, hereditary or acquired angioedema, allergic angioedema [eg, food, insect bite or sting, evident clinical response to antihistamines and/or corticosteroids], anaphylaxis, trauma, abscess or infection or associated disease, local inflammation, local tumor, post-operative or post-radiogenic edema, salivary gland disorders, other [non-ACE inhibitor] drug-induced angioedema).
- •Patients with a family history of recurrent angioedema.
- •Patients who have had a previous episode(s) of angioedema while not on ACE inhibitor therapy.
- •Patients with acute urticaria (itchy, erythematous wheals).
- •Patients who have an intervention to support the airway (eg, intubation, tracheotomy, cricothyrotomy) due to the current attack of angioedema.
- •Patient has any of the following vascular conditions that, in the judgment of the investigator, would be a contraindication to participation in the study.
- •Unstable angina pectoris or acute myocardial ischemia
- •Hypertensive urgency or emergency (diastolic blood pressure [DBP] >120 mm Hg or systolic blood pressure [SBP] >180 mm Hg)
- •Within 1 month of a stroke or transient ischemic attack
- •New York Heart Association (NYHA) heart failure class IV
- •Patient has a serious or acute condition or illness that, in the judgment of the investigator, would interfere with evaluating the safety and/or efficacy assessments of the study (eg, a condition or illness requiring hemodialysis).
- •Patient is pregnant or breast feeding.
- •Patient has participated in another investigational study in the past 30 days.
- •Patient is unable to understand the nature, scope, and possible consequences of the protocol, or is unlikely or unable to comply with the protocol assessments, or is unlikely to complete the study for any reason.
- •Patients who are not suitable for the study in the opinion of the investigator.
- •Patient has experienced hypersensitivity to the active substance of the investigational product or to any of its excipients.
研究组 & 干预措施
Icatibant
Icatibant at a dose of 30 mg will be administered as a single subcutaneous injection
干预措施: Icatibant (Drug)
Placebo
Placebo will be administered as a single subcutaneous injection
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)
时间窗: From start of study drug administration (Day 0) up to follow-up (Day 5)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time to Meeting Discharge Criteria (TMDC)
时间窗: Day 0 up to Day 5
TMDC was based on the investigator-assessed angioedema-associated upper airway symptom assessments. It was calculated from the time of study drug administration to the earliest time point at which the symptoms of difficulty breathing and difficulty swallowing were absent and the symptoms of voice change and tongue swelling were mild or absent and all subsequent assessments continued to satisfy these conditions. These symptoms were evaluated by the investigator using a 5-point grading scale (0=absent, 1=mild, 2=moderate, 3=severe, and 4=very severe). TMDC was analysed using Kaplan-Meier estimates.
Number of Participants With Clinically Significant Changes in Laboratory Evaluation, Vital Signs, Electrocardiogram (ECG) and Physical Examination
时间窗: Day 0 to Day 5
During laboratory evaluation, serum chemistry and hematology blood tests, and urinalysis were performed. Vital signs parameters included evaluation of pulse rate and systolic and diastolic blood pressure. Standard 12-lead ECGs were performed and ECG recordings were read locally at the study site by a cardiologist. Physical examination was performed with examination of major body systems per routine clinical practice.
Number of Participants With Treatment Emergent Injection Site Reaction
时间窗: Day 0 to Day 5
Injection site reaction included erythema, swelling, cutaneous pain, burning sensation, itching and warm sensation
次要结局
- Time to Onset of Symptom Relief (TOSR)(Day 0 up to Day 5)
- Number of Participants Experienced Airway Intervention Due to ACE-I-induced Angioedema(Day 0 up to Day 5)
- Number of Participants Admitted to Hospital or Intensive Care Unit (ICU)(Day 0 up to Day 5)
- Percentage of Participants With Time to Meeting Discharge Criteria (TMDC) at Specified Time Points(4, 6, and 8 hours post treatment)
- Number of Participants Experienced ACE-I-induced Angioedema Attack Following Study Drug Administration(Day 0 up to Day 5)