Trial Outcomes & Findings for Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE) (NCT NCT00500656)

Last Updated: 2021-06-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

85 participants

Primary outcome timeframe

2 days

Results posted on

2021-06-09

Participant Flow

85 patients participated in the study(36 in the icatibant group and 38 in the tranexamic acid group)3 patients with laryngeal symptoms at Baseline.8 Patients 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

Participant milestones

Participant milestones
Measure	Randomized Controlled -Icatibant Patients who were randomized to icatibant + Oral placebo (hard capsule matched to tranexamic acid) in the controlled phase after they had an eligible first in-study attack.	Randomized Controlled-Tranexamic Acid Patients who were randomized to received oral Tranexamic acid + S.C. placebo(solution for injection, matched to icatibant for injection) in the controlled phase after they had an eligible first in-study attack.	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.	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
Controlled Phase STARTED	36	38	3	8
Controlled Phase COMPLETED	26	28	2	0
Controlled Phase NOT COMPLETED	10	10	1	8
Open Label Extension (OLE) Phase STARTED	23	21	2	8
Open Label Extension (OLE) Phase COMPLETED	16	9	1	6
Open Label Extension (OLE) Phase NOT COMPLETED	7	12	1	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized Controlled -Icatibant n=36 Participants Patients who were randomized to icatibant + Oral placebo (hard capsule matched to tranexamic acid) in the controlled phase after they had an eligible first in-study attack.	Randomized Controlled-Tranexamic Acid n=38 Participants Patients who were randomized to received oral Tranexamic acid + S.C. placebo(solution for injection, matched to icatibant for injection) in the controlled phase after they had an eligible first in-study attack.	Controlled Open-label / Laryngeal Attack n=3 Participants Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.	Untreated Patients at the Baseline n=8 Participants 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	Total n=85 Participants Total of all reporting groups
Age, Continuous	40.4 years STANDARD_DEVIATION 13.59 • n=5 Participants	41.9 years STANDARD_DEVIATION 12.36 • n=7 Participants	35.0 years STANDARD_DEVIATION 11.36 • n=5 Participants	40.6 years STANDARD_DEVIATION 13.51 • n=4 Participants	40.9 years STANDARD_DEVIATION 12.8 • n=21 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	23 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants	55 Participants n=21 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	15 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	30 Participants n=21 Participants
Region of Enrollment Austria	3 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants
Region of Enrollment France	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Region of Enrollment Germany	13 Participants n=5 Participants	12 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	25 Participants n=21 Participants
Region of Enrollment Hungary	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants
Region of Enrollment Ireland	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment Israel	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants
Region of Enrollment Italy	3 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Region of Enrollment Lithuania	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Region of Enrollment Poland	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Region of Enrollment Sweden	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Region of Enrollment Switzerland	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants

PRIMARY outcome

Timeframe: 2 days

Outcome measures

Outcome measures
Measure	Randomized Controlled -Icatibant n=36 Participants Patients who were randomized to icatibant + Oral placebo (hard capsule matched to tranexamic acid) in the controlled phase after they had an eligible first in-study attack.	Randomized Controlled-Tranexamic Acid n=38 Participants Patients who were randomized to received oral Tranexamic acid + S.C. placebo(solution for injection, matched to icatibant for injection) in the controlled phase after they had an eligible first in-study attack.
Time to Onset of Symptom Relief.	2.0 Hours Interval 1.0 to 3.5	12.0 Hours Interval 3.5 to 25.4

SECONDARY outcome

Timeframe: 48 hours

Almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least three consecutive measurements for all symptoms.

Outcome measures

Outcome measures
Measure	Randomized Controlled -Icatibant n=36 Participants Patients who were randomized to icatibant + Oral placebo (hard capsule matched to tranexamic acid) in the controlled phase after they had an eligible first in-study attack.	Randomized Controlled-Tranexamic Acid n=38 Participants Patients who were randomized to received oral Tranexamic acid + S.C. placebo(solution for injection, matched to icatibant for injection) in the controlled phase after they had an eligible first in-study attack.
Time to Almost Complete Symptom Relief	10.0 Hours Interval 2.8 to 23.2	51.0 Hours Interval 12.0 to 79.5

Adverse Events

Controlled Phase- Icatibant (Randomized Subjects )

Serious events: 4 serious events

Other events: 19 other events

Deaths: 0 deaths

Controlled Phase- Tranexamic Acid (Randomized Subjects)

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Open Label Extension Phase- Icatibant (Previously Randomized)

Serious events: 9 serious events

Other events: 31 other events

Deaths: 0 deaths

Open Label Extension Phase (Subjects w/ Laryngeal Attack)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Open Label Extension Phase(Untreated Patients at the Baseline

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Controlled Phase- Icatibant (Randomized Subjects ) n=36 participants at risk Patients who were randomized to icatibant+ oral placebo in the controlled phase and experienced adverse events while participating in the controlled phase	Controlled Phase- Tranexamic Acid (Randomized Subjects) n=38 participants at risk Patients who were randomized to Tranexamic acid+ S.C. placebo in the controlled phase and experienced adverse events while participating in the controlled phase.	Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) n=3 participants at risk This represents adverse events during the controlled phase that were experienced by Patients with laryngeal symptoms at the baseline and were treated with open label icatibant during the controlled phase.	Open Label Extension Phase- Icatibant (Previously Randomized) n=44 participants at risk Patients who were randomized to either icatibant+ oral placebo or Tranexamic acid+ S.C. placebo in the controlled phase and experienced adverse events while participating in the open label extension phase.	Open Label Extension Phase (Subjects w/ Laryngeal Attack) n=2 participants at risk This represents adverse events during the open label extension phase that were experienced by Patients with laryngeal symptoms at the baseline and got treated with open label icatibant during the controlled phase and Open label extension phase.	Open Label Extension Phase(Untreated Patients at the Baseline n=8 participants at risk This represents adverse events experienced by 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.
Congenital, familial and genetic disorders Hereditary Angioedema	5.6% 2/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	33.3% 1/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	6.8% 3/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	50.0% 1/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Cardiac disorders Aortic Value Sclerosis	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.6% 1/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
General disorders Sudden Cardiac Death	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.6% 1/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Hepatobiliary disorders Cholelithiasis	2.8% 1/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Cystitis	2.8% 1/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Gastroenteritis	2.8% 1/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	4.5% 2/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Vascular disorders Hypertensive Crisis	2.8% 1/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Cardiac disorders Coronary Artery Disease	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Injury, poisoning and procedural complications Head Injury	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Injury, poisoning and procedural complications Wound	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Investigations Pancreatic Enzymes Increased	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix Carcinoma Stage 0	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Psychiatric disorders Suicide Attempt	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Renal and urinary disorders Renal Failure	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Surgical and medical procedures Tooth Extraction	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Urinary Track Infection Bacterial	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.

Other adverse events

Other adverse events
Measure	Controlled Phase- Icatibant (Randomized Subjects ) n=36 participants at risk Patients who were randomized to icatibant+ oral placebo in the controlled phase and experienced adverse events while participating in the controlled phase	Controlled Phase- Tranexamic Acid (Randomized Subjects) n=38 participants at risk Patients who were randomized to Tranexamic acid+ S.C. placebo in the controlled phase and experienced adverse events while participating in the controlled phase.	Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) n=3 participants at risk This represents adverse events during the controlled phase that were experienced by Patients with laryngeal symptoms at the baseline and were treated with open label icatibant during the controlled phase.	Open Label Extension Phase- Icatibant (Previously Randomized) n=44 participants at risk Patients who were randomized to either icatibant+ oral placebo or Tranexamic acid+ S.C. placebo in the controlled phase and experienced adverse events while participating in the open label extension phase.	Open Label Extension Phase (Subjects w/ Laryngeal Attack) n=2 participants at risk This represents adverse events during the open label extension phase that were experienced by Patients with laryngeal symptoms at the baseline and got treated with open label icatibant during the controlled phase and Open label extension phase.	Open Label Extension Phase(Untreated Patients at the Baseline n=8 participants at risk This represents adverse events experienced by 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.
Congenital, familial and genetic disorders Hereditary Angioedema	27.8% 10/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	15.8% 6/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	33.3% 1/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	22.7% 10/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	50.0% 1/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	12.5% 1/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
General disorders Injection Site Reaction	5.6% 2/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Nasopharyngitis	5.6% 2/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	7.9% 3/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	9.1% 4/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Pharyngitis	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.6% 1/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	6.8% 3/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Nervous system disorders Headache	5.6% 2/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	5.3% 2/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Urinary Track Infection	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	13.6% 6/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Gingival Infection	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	50.0% 1/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Dental Caries	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	12.5% 1/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Respiratory Track Infection	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	12.5% 1/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Nervous system disorders Dizziness	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	12.5% 1/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	12.5% 1/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Surgical and medical procedures Dental Operation	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	12.5% 1/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Blood and lymphatic system disorders Blood and Lymphatic system disorders	0.00% 0/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	5.3% 2/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.3% 1/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Injury, poisoning and procedural complications Injury, poisoning and procedual complications	8.3% 3/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.6% 1/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	6.8% 3/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	5.6% 2/36 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	2.6% 1/38 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	6.8% 3/44 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/2 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60