Evaluation of Ecallantide for Treatment of Angiotensin Converting Enzyme (ACE) Inhibitor Induced Angioedema

Study Overview
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Brief Summary
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A double-blind, randomized, controlled trial comparing the safety and effectiveness of conventional therapy with ecallantide to conventional therapy with placebo.

Official Title
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Evaluation of Ecallantide for the Acute Treatment of Angiotensin Converting Enzyme Inhibitor Induced Angioedema

Conditions
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ACE Inhibitor Induced Angioedema

Intervention / Treatment
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* Drug: ecallantide 60 mg
* Drug: ecallantide 30 mg
* Drug: ecallantide 10 mg
* Drug: placebo
* Drug: placebo match for 30 mg ecallantide arm
* Drug: placebo match for 10 mg ecallantide arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18 years of age or older Must currently be on ACE inhibitor therapy and have received a dose within 36 hours Presenting with ACEIA of the head/neck region within 12 hours after onset All females must have a negative urine pregnancy test prior to administration of the study drug. Those who have had a total hysterectomy, bilateral oophorectomy or are two years post-menopausal do not require a pregnancy test. Exclusion Criteria: Hypersensitivity to ecallantide Pregnancy or breast feeding Patients who have had angioedema and were not concurrently on an ACE inhibitor Patients exhibiting urticaria Patients who are intubated or who have a tracheostomy related to the current episode of angioedema Opinion of the investigator that the patient would not be a good candidate Participation in another investigational study within 30 days prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ecallantide 10mg<br>Administered as one 3 mL SC injection containing 10 mg ecallantide and one 3 mL SC injection of matching placebo. | Drug: ecallantide 10 mg<br>* Administered as one 3 mL SC injection containing 10 mg ecallantide.<br>Drug: placebo match for 10 mg ecallantide arm<br>* One 3 mL SC injection of matching placebo given to subjects randomized to the 10 mg ecallantide arm.<br>|
| Placebo Comparator: placebo<br>Administered as two SC 3 mL injections | Drug: placebo<br>* Administered as two SC 3 mL injections<br>|
| Active Comparator: ecallantide 60mg<br>Administered as two 3 mL SC injections, each containing 30 mg ecallantide | Drug: ecallantide 60 mg<br>* Administered as two 3 mL SC injections, each containing 30 mg ecallantide<br>|
| Active Comparator: ecallantide 30mg<br>Administered as one 3 mL SC injection containing 30 mg ecallantide and one 3 mL SC injection of matching placebo. | Drug: ecallantide 30 mg<br>* Administered as one 3 mL SC injection containing 30 mg ecallantide<br>Drug: placebo match for 30 mg ecallantide arm<br>* One 3 mL SC injection of matching placebo given to subjects randomized to the 30 mg ecallantide arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Efficacy of Ecallantide | Compare the proportion of patients meeting prespecified discharge criteria in the group receiving ecallantide with conventional therapy to patients receiving placebo with conventional therapy. Patients were evaluated against 6 discharge eligibility criteria at 1,2,3,4,5, and 6 hours after study drug administration or until discharged from the ER. A responder was defined as a patient meeting all six discharge eligibility criteria as below: • Improvement of edema to a little better or a lot better as assessed by health care provider using a five point scale • Stable vital signs (within an acceptable range) • Absence of stridor • Absence of dyspnea or use of accessory muscles during respiration • Absence of drooling • Able to drink without difficulty | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Symptom Resolution Based on the Visual Analog Scale (VAS) | Compare the time to onset of symptom resolution between the ecallantide-treated and placebo-treated groups. The patient assessed severity of the angioedema attack using a VAS at baseline and following study drug administration every 15 minutes for the first 2 hours and then every 30 minutes through 6 hours post dosing or until the time of discharge from the ER (whichever occurred first). The scale ranged from totally resolved to very severe. | 6 hours |