Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Time to Onset of Symptom Relief (TOSR) |
The TOSR was defined as a 50 percent (%) reduction from the pre-treatment score in the 3-symptom composite VAS score for non-laryngeal attacks and 5-symptom composite VAS score for laryngeal attacks. A VAS utilizes a scale consisting of a 100 millimeter (mm) horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The participant should draw a vertical line at the point along the scale that represents the current status of the measured symptom. Composite VAS scores were calculated as the average of VAS measurements for skin swelling, skin pain, and abdominal pain (3-symptom composite) for non-laryngeal attacks and for skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change (5-symptom composite) for laryngeal attacks. |
Baseline up to 120 hours post-treatment |
|
Secondary |
Time to Onset of Primary Symptom Relief (TOSR-P) |
Primary symptom relief was based on the participant-assessed VAS score for a single primary symptom (determined by edema location) and corresponds to a reduction by 31 mm at a pretreatment VAS of 100 mm and by 21 mm at a pretreatment VAS of 30 mm. If the primary symptom pretreatment VAS less than (<) 30 mm, then primary symptom relief was defined as 68% reduction from pretreatment. A VAS utilizes a scale consisting of a 100 millimeter (mm) horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The TOSR-P was calculated from the time of icatibant administration to the onset of primary symptom relief. |
Baseline up to 120 hours post-treatment |
|
Secondary |
Change From Baseline in the Composite Visual Analog Scale (VAS) Score |
A VAS utilizes a scale consisting of a 100 mm horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The participant should draw a vertical line at the point along the scale that represents the current status of the measured symptom. Composite VAS scores was calculated as the average of VAS measurements for skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change (5-symptom composite) for laryngeal attacks and as the average of VAS measurements for skin swelling, skin pain and abdominal pain (3-symptom composite) for non-laryngeal attacks. Change from baseline in the composite VAS score was reported. |
Baseline, 2, 4 and 8 hours post-treatment |
|
Secondary |
Composite Symptom Score (SS) Assessed by Investigator |
The investigator-assessed composite symptom score was calculated as an average of abdominal tenderness, nausea, vomiting, diarrhea, skin pain, erythema, skin irritation, and skin swelling (8 symptoms) for non-laryngeal attacks and the average of abdominal tenderness, nausea, vomiting, diarrhea, skin pain, erythema, skin irritation, skin swelling, dysphagia, voice change, breathing difficulties, stridor, and asphyxia (13 symptoms) for laryngeal attacks using the following 5-point scale 0 = none (absence of symptoms); 1 = mild (no to mild interference with daily activities); 2 = moderate (moderate interference with daily activities); 3 = severe (severe interference with daily activities); 4 = very severe (very severe interference with daily activities). Here the composite SS assessed by investigator was reported. |
8 hours post dose |
|
Secondary |
Composite Symptom Score (SS) Assessed by Participant |
The participant-assessed composite symptom score was calculated as an average of abdominal pain, nausea, vomiting, diarrhea, skin pain, erythema, skin irritation, and skin swelling (8 symptoms) for non-laryngeal attacks and the average of abdominal pain, nausea, vomiting, diarrhea, skin pain, erythema,skin irritation, skin swelling, dysphagia and voice change (10 symptoms) for laryngeal attacks using the following 5-point scale 0 = none (absence of symptoms); 1 = mild (no to mild interference with daily activities); 2 = moderate (moderate interference with daily activities); 3 = severe (severe interference with daily activities); 4 = very severe (very severe interference with daily activities). Here the composite SS assessed by participant was reported. |
8 hours post dose |
|
Secondary |
Investigator Global Assessment |
The investigator was made a global assessment (that is [i.e.] consideration of all abdominal symptoms combined, all cutaneous symptoms combined and/or all laryngeal symptoms combined) using the following 5-point scale, where the symptoms were scored from 0 for "absence of symptoms" to 4 for "very severe": 0 = none (absence of symptoms); 1 = mild (no to mild interference with daily activities); 2 = moderate (moderate interference with daily activities); 3 = severe (severe interference with daily activities); 4 = very severe (very severe interference with daily activities). |
2, 4 and 8 hours post dose |
|
Secondary |
Time to Initial Symptom Improvement by Investigator |
Time to initial symptom improvement was evaluated by the investigator; each were asked to record the time at which they perceived initial improvement of symptoms. Time to initial symptom improvement was calculated from the time of icatibant administration to the time reported by the investigator of initial improvement of symptoms. |
Baseline up to 120 hours post-treatment |
|
Secondary |
Time to Initial Symptom Improvement by Participants |
Time to initial symptom improvement was evaluated by the participants; each were asked to record the time at which they perceived initial improvement of symptoms. Time to initial symptom improvement was calculated from the time of icatibant administration to the time reported by the participant of initial improvement of symptoms. |
Baseline up to 120 hours post-treatment |
|
Secondary |
Time to Almost Complete Symptom Relief As Assessed by Visual Analog Scale (VAS) Score |
Time to almost complete symptom relief was calculated from the time of icatibant administration to almost complete symptom relief. Almost complete symptom relief was determined retrospectively as the earliest of three consecutive non-missing measurements for which all VAS scores < 10 mm. A VAS utilizes a scale consisting of a 100 millimeter (mm) horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The participant should draw a vertical line at the point along the scale that represents the current status of the measured symptom. |
Baseline up to 120 hours post-treatment |
|
Secondary |
Maximum Observed Plasma Concentration (Cmax) of Icatibant After a Single Subcutaneous (SC) Administration of Icatibant |
The Cmax was estimated by a population PK modeling approach. The Cmax of icatibant was reported. |
Baseline, 0.75, 2 hours post-treatment |
|
Secondary |
Area Under the Concentration-time Curve From 0 to 2 Hours (AUC0-2) After a Single Subcutaneous (SC) Administration of Icatibant |
The AUC0-2 was estimated by a population PK modeling approach. The AUC0-2 of Icatibant was reported. |
Baseline, 0.75, 2 hours post-treatment |
|
Secondary |
Area Under the Concentration-time Curve From 0 to 4 Hours (AUC0-4) After a Single Subcutaneous (SC) Administration of Icatibant |
The AUC0-4 was estimated by a population PK modeling approach. The AUC0-4 of Icatibant was reported. |
Baseline, 0.75, 2 hours post-treatment |
|
Secondary |
Area Under the Concentration-time Curve From 0 to 6 Hours (AUC0-6) After a Single Subcutaneous (SC) Administration of Icatibant |
The AUC0-6 was estimated by a population PK modeling approach. The AUC0-6 of Icatibant was reported. |
Baseline, 0.75, 2 hours post-treatment |
|
Secondary |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurred in any phase of a clinical study, whether or not considered investigational product related. The TEAEs were defined as all AEs occurred on or after the time of study drug administration. |
From start of study drug administration to follow-up (up to 10 days) |
|
Secondary |
Number of Participants With Injection Site Reactions Reported as Adverse Event (AE) |
Number of participants with injection site reactions (erythema, swelling, cutaneous pain, burning sensation, itching/pruritus, and warm sensation) were reported. |
From start of study drug administration to follow-up (up to 10 days) |
|
Secondary |
Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Adverse Event (AE) |
Clinical laboratory tests included serum chemistry, hematology, urinalysis and coagulation were assessed. Number of participants with clinically significant changes in clinical laboratory tests were reported. |
From start of study drug administration to follow-up (up to 10 days) |
|
Secondary |
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Event (AE) |
Vital signs included pulse rate, blood pressure, respiration rate, and temperature. The number of participants with clinically significant changes in vital signs were reported. |
From start of study drug administration to follow-up (up to 10 days) |
|
Secondary |
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Adverse Event (AE) |
A standard 12-lead ECG was performed. The number of participants who reported clinically significant changes in ECGs were reported. |
From start of study drug administration to follow-up (up to 10 days) |
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