Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 10 of 23 for:    ICATIBANT

Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE) (FAST2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00500656
Recruitment Status : Completed
First Posted : July 13, 2007
Results First Posted : June 9, 2014
Last Update Posted : February 16, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hereditary Angioedema
Interventions Drug: Icatibant
Drug: Tranexamic Acid
Drug: Oral Placebo
Drug: S.C. Placebo
Enrollment 85
Recruitment Details  
Pre-assignment Details 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
Arm/Group Title Randomized Controlled -Icatibant Randomized Controlled-Tranexamic Acid Controlled Open-label / Laryngeal Attack Untreated Patients at the Baseline
Hide Arm/Group Description 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. 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. Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase. 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
Period Title: Controlled Phase
Started 36 38 3 8
Completed 26 28 2 0
Not Completed 10 10 1 8
Period Title: Open Label Extension (OLE) Phase
Started 23 [1] 21 [2] 2 8 [3]
Completed 16 9 1 6
Not Completed 7 12 1 2
[1]
3 Subjects did not experience an angioedema attack after their first attack in the controlled phase
[2]
7 Subjects did not experience an angioedema attack after their first attack in the controlled phase
[3]
Subjects did not experience an angioedema attack during the controlled phase
Arm/Group Title Randomized Controlled -Icatibant Randomized Controlled-Tranexamic Acid Controlled Open-label / Laryngeal Attack Untreated Patients at the Baseline Total
Hide Arm/Group Description 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. 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. Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase. 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 of all reporting groups
Overall Number of Baseline Participants 36 38 3 8 85
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 38 participants 3 participants 8 participants 85 participants
40.4  (13.59) 41.9  (12.36) 35.0  (11.36) 40.6  (13.51) 40.9  (12.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 38 participants 3 participants 8 participants 85 participants
Female
24
  66.7%
23
  60.5%
1
  33.3%
7
  87.5%
55
  64.7%
Male
12
  33.3%
15
  39.5%
2
  66.7%
1
  12.5%
30
  35.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 38 participants 3 participants 8 participants 85 participants
Austria 3 4 0 1 8
France 3 1 0 2 6
Germany 13 12 0 0 25
Hungary 3 3 0 0 6
Ireland 0 1 0 0 1
Israel 4 4 3 4 15
Italy 3 5 0 1 9
Lithuania 1 2 0 0 3
Poland 1 2 0 0 3
Sweden 3 2 0 0 5
Switzerland 2 2 0 0 4
1.Primary Outcome
Title Time to Onset of Symptom Relief.
Hide Description

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.

Time Frame 2 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Randomized Controlled -Icatibant Randomized Controlled-Tranexamic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 36 38
Median (Inter-Quartile Range)
Unit of Measure: Hours
2.0
(1.0 to 3.5)
12.0
(3.5 to 25.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Controlled -Icatibant, Randomized Controlled-Tranexamic Acid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method The Wilcoxon version of the log rank
Comments The median time to onset was calculated using Kaplan Meier methodology. The Wilcoxon version of the log rank test of SAS was used
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.475
Confidence Interval (2-Sided) 95%
1.901 to 6.355
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time to Almost Complete Symptom Relief
Hide Description 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.
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Randomized Controlled -Icatibant Randomized Controlled-Tranexamic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 36 38
Median (Inter-Quartile Range)
Unit of Measure: Hours
10.0
(2.8 to 23.2)
51.0
(12.0 to 79.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Controlled -Icatibant, Randomized Controlled-Tranexamic Acid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method The Wilcoxon version of the log rank
Comments The median time to almost complete symptom relief was calculated using Kaplan Meier methodology.The Wilcoxon version of the log rank test SAS was used
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Controlled Phase- Icatibant (Randomized Subjects ) Controlled Phase- Tranexamic Acid (Randomized Subjects) Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) Open Label Extension Phase- Icatibant (Previously Randomized) Open Label Extension Phase (Subjects w/ Laryngeal Attack) Open Label Extension Phase(Untreated Patients at the Baseline
Hide Arm/Group Description Patients who were randomized to icatibant+ oral placebo in the controlled phase and experienced adverse events while participating in the controlled phase Patients who were randomized to Tranexamic acid+ S.C. placebo in the controlled phase and experienced adverse events while participating in the controlled phase. 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. 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. 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. 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.
All-Cause Mortality
Controlled Phase- Icatibant (Randomized Subjects ) Controlled Phase- Tranexamic Acid (Randomized Subjects) Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) Open Label Extension Phase- Icatibant (Previously Randomized) Open Label Extension Phase (Subjects w/ Laryngeal Attack) Open Label Extension Phase(Untreated Patients at the Baseline
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Controlled Phase- Icatibant (Randomized Subjects ) Controlled Phase- Tranexamic Acid (Randomized Subjects) Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) Open Label Extension Phase- Icatibant (Previously Randomized) Open Label Extension Phase (Subjects w/ Laryngeal Attack) Open Label Extension Phase(Untreated Patients at the Baseline
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/36 (11.11%)   1/38 (2.63%)   1/3 (33.33%)   9/44 (20.45%)   1/2 (50.00%)   0/8 (0.00%) 
Cardiac disorders             
Aortic Value Sclerosis  1  0/36 (0.00%)  1/38 (2.63%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  0/8 (0.00%) 
Coronary Artery Disease  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Congenital, familial and genetic disorders             
Hereditary Angioedema  1  2/36 (5.56%)  0/38 (0.00%)  1/3 (33.33%)  3/44 (6.82%)  1/2 (50.00%)  0/8 (0.00%) 
General disorders             
Sudden Cardiac Death  1  0/36 (0.00%)  1/38 (2.63%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  0/8 (0.00%) 
Hepatobiliary disorders             
Cholelithiasis  1  1/36 (2.78%)  0/38 (0.00%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  0/8 (0.00%) 
Infections and infestations             
Cystitis  1  1/36 (2.78%)  0/38 (0.00%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  0/8 (0.00%) 
Gastroenteritis  1  1/36 (2.78%)  0/38 (0.00%)  0/3 (0.00%)  2/44 (4.55%)  0/2 (0.00%)  0/8 (0.00%) 
Urinary Track Infection Bacterial  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Injury, poisoning and procedural complications             
Head Injury  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Road Traffic Accident  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Wound  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Investigations             
Pancreatic Enzymes Increased  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders             
Myalgia  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Cervix Carcinoma Stage 0  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Psychiatric disorders             
Suicide Attempt  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Renal and urinary disorders             
Renal Failure  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Surgical and medical procedures             
Tooth Extraction  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Vascular disorders             
Hypertensive Crisis  1  1/36 (2.78%)  0/38 (0.00%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  0/8 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 8.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Controlled Phase- Icatibant (Randomized Subjects ) Controlled Phase- Tranexamic Acid (Randomized Subjects) Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) Open Label Extension Phase- Icatibant (Previously Randomized) Open Label Extension Phase (Subjects w/ Laryngeal Attack) Open Label Extension Phase(Untreated Patients at the Baseline
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   19/36 (52.78%)   16/38 (42.11%)   1/3 (33.33%)   31/44 (70.45%)   1/2 (50.00%)   4/8 (50.00%) 
Blood and lymphatic system disorders             
Blood and Lymphatic system disorders  2  0/36 (0.00%)  2/38 (5.26%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Congenital, familial and genetic disorders             
Hereditary Angioedema  1  10/36 (27.78%)  6/38 (15.79%)  1/3 (33.33%)  10/44 (22.73%)  1/2 (50.00%)  1/8 (12.50%) 
General disorders             
Injection Site Reaction  1  2/36 (5.56%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  0/8 (0.00%) 
Infections and infestations             
Nasopharyngitis  1  2/36 (5.56%)  3/38 (7.89%)  0/3 (0.00%)  4/44 (9.09%)  0/2 (0.00%)  0/8 (0.00%) 
Pharyngitis  1  0/36 (0.00%)  1/38 (2.63%)  0/3 (0.00%)  3/44 (6.82%)  0/2 (0.00%)  0/8 (0.00%) 
Urinary Track Infection  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  6/44 (13.64%)  0/2 (0.00%)  0/8 (0.00%) 
Gingival Infection  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  0/44 (0.00%)  1/2 (50.00%)  0/8 (0.00%) 
Dental Caries  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  1/8 (12.50%) 
Respiratory Track Infection  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  1/44 (2.27%)  0/2 (0.00%)  1/8 (12.50%) 
Injury, poisoning and procedural complications             
Injury, poisoning and procedual complications  2  3/36 (8.33%)  1/38 (2.63%)  0/3 (0.00%)  3/44 (6.82%)  0/2 (0.00%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders             
Musculoskeletal and connective tissue disorders  2  2/36 (5.56%)  1/38 (2.63%)  0/3 (0.00%)  3/44 (6.82%)  0/2 (0.00%)  0/8 (0.00%) 
Nervous system disorders             
Headache  1  2/36 (5.56%)  2/38 (5.26%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  0/8 (0.00%) 
Dizziness  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  1/8 (12.50%) 
Skin and subcutaneous tissue disorders             
Pruritus  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  1/8 (12.50%) 
Surgical and medical procedures             
Dental Operation  1  0/36 (0.00%)  0/38 (0.00%)  0/3 (0.00%)  0/44 (0.00%)  0/2 (0.00%)  1/8 (12.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 8.1
2
Term from vocabulary, Organ system
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Alan Kimura, MD, PhD
Organization: Shire Human Genetic Therapies, Inc.
Phone: 781-482-0738
EMail: akimura@shire.com
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00500656     History of Changes
Other Study ID Numbers: JE049 #2102
2004-001540-71 ( EudraCT Number )
First Submitted: July 12, 2007
First Posted: July 13, 2007
Results First Submitted: October 30, 2013
Results First Posted: June 9, 2014
Last Update Posted: February 16, 2015