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Trial record 6 of 23 for:    ICATIBANT

Blinded Safety & Efficacy Placebo Controlled Study of Icatibant for Angiotensin Converting Enzyme Inhibitor Induced Angioedema

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ClinicalTrials.gov Identifier: NCT01919801
Recruitment Status : Completed
First Posted : August 9, 2013
Results First Posted : October 10, 2016
Last Update Posted : December 13, 2018
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Condition Angiotensin Converting Enzyme Inhibitor Induced Angioedema
Interventions Drug: Icatibant
Drug: Placebo
Enrollment 118
Recruitment Details The study was conducted at 59 sites in the United States, United Kingdom, Israel and Canada.
Pre-assignment Details Overall 121 participants were randomized, of which 118 received the study medication, and 117 completed the study.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description Participants received a single dose of icatibant 30 milligram (mg) subcutaneous (SC) injection within 12 hours after the onset of the angiotensin-converting enzyme inhibitor (ACE-I) induced angioedema attack. Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Period Title: Overall Study
Started 61 60
Completed 60 57
Not Completed 1 3
Reason Not Completed
Withdrawal by Subject             1             0
Physician Decision             0             1
Lost to Follow-up             0             1
Other             0             1
Arm/Group Title Icatibant 30 mg Placebo Total
Hide Arm/Group Description Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack. Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack. Total of all reporting groups
Overall Number of Baseline Participants 61 60 121
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants 60 participants 121 participants
60.9  (12.1) 61.8  (13.4) 61.4  (12.7)
[1]
Measure Description: Age was calculated as the difference between date of birth and date of informed consent, rounded to 1 decimal place.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 60 participants 121 participants
Female
27
  44.3%
35
  58.3%
62
  51.2%
Male
34
  55.7%
25
  41.7%
59
  48.8%
1.Primary Outcome
Title Time to Meeting Discharge Criteria (TMDC)
Hide Description 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.
Time Frame Day 0 up to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 61 60
Median (Inter-Quartile Range)
Unit of Measure: days
4.03
(2.03 to 6.00)
4.00
(1.03 to 6.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Icatibant 30 mg, Placebo
Comments A total of 121 participants were analysed, however 3 participants did not receive the study medication and were censored at time 0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.633
Comments Test was performed using a weighted log-rank test called the Peto-Prentice test with a global 2-sided significance level of 5% after adjusting for stratification factors (race, and severity) in the ITT population.
Method Adjusted Peto-Prentice
Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)
Hide Description 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 Frame From start of study drug administration (Day 0) up to follow-up (Day 5)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received the study drug.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 60 58
Measure Type: Number
Unit of Measure: participants
Participants with TEAEs 27 21
Participants with TESAEs 2 1
3.Primary Outcome
Title Number of Participants With Treatment Emergent Injection Site Reaction
Hide Description Injection site reaction included erythema, swelling, cutaneous pain, burning sensation, itching and warm sensation
Time Frame Day 0 to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 60 58
Measure Type: Number
Unit of Measure: participants
Erythema 31 13
Swelling 17 13
Cutaneous pain 10 7
Burning sensation 15 7
Itching 13 6
Warm sensation 16 8
4.Primary Outcome
Title Number of Participants With Clinically Significant Changes in Laboratory Evaluation, Vital Signs, Electrocardiogram (ECG) and Physical Examination
Hide Description 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.
Time Frame Day 0 to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 60 58
Measure Type: Number
Unit of Measure: participants
0 0
5.Secondary Outcome
Title Time to Onset of Symptom Relief (TOSR)
Hide Description TOSR was calculated for the individual symptoms with pre-treatment scores of 2 (moderate) or more improved by at least 1 severity grade and the individual symptoms with pretreatment scores of 0 or 1 (absent or mild) were scored again at 0 or 1 and all the subsequent assessments continued to satisfy this condition. Time-to-event data were summarized using Kaplan-Meier estimates.
Time Frame Day 0 up to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 61 60
Median (Inter-Quartile Range)
Unit of Measure: days
2.00
(0.58 to 3.08)
1.55
(0.50 to 3.88)
6.Secondary Outcome
Title Number of Participants Experienced Airway Intervention Due to ACE-I-induced Angioedema
Hide Description Airway Intervention included intubation, tracheotomy, cricothyrotomy.
Time Frame Day 0 up to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent to treat (mITT) population included all randomized participants who received the study drug.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 60 58
Measure Type: Number
Unit of Measure: participants
1 0
7.Secondary Outcome
Title Number of Participants Admitted to Hospital or Intensive Care Unit (ICU)
Hide Description Number of participants with and without an occurrence of admission to the hospital (inpatient) or ICU post-treatment due to the ACE-I-induced angioedema attack were described.
Time Frame Day 0 up to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 60 58
Measure Type: Number
Unit of Measure: participants
22 22
8.Secondary Outcome
Title Number of Participants Experienced ACE-I-induced Angioedema Attack Following Study Drug Administration
Hide Description Number of participants with the use of conventional medications (corticosteroids, antihistamines, epinephrine) for the treatment of symptoms of the ACE-I- induced angioedema attack following study drug administration were presented.
Time Frame Day 0 up to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 60 58
Measure Type: Number
Unit of Measure: participants
35 35
9.Secondary Outcome
Title Percentage of Participants With Time to Meeting Discharge Criteria (TMDC) at Specified Time Points
Hide Description 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.
Time Frame 4, 6, and 8 hours post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 60 58
Measure Type: Number
Unit of Measure: percentage of participants
At 4 hours post treatment 55.0 60.3
At 6 hours post treatment 78.3 75.9
At 8 hours post treatment 91.7 91.4
10.Other Pre-specified Outcome
Title Area Under the Plasma Concentration Versus Time Curve (AUC) of Icatibant and Its Metabolites (M1 and M2)
Time Frame 0.75 and 2 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population.
Arm/Group Title Icatibant 30 mg
Hide Arm/Group Description:
Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
Overall Number of Participants Analyzed 21
Mean (Standard Deviation)
Unit of Measure: hours*nanogram per milliliter (h*ng/mL)
Icatibant 2530  (786)
Metabolite M1 2890  (813)
Metabolite M2 3180  (931)
Time Frame From start of study treatment up to Day 5
Adverse Event Reporting Description Injection site reactions were reported separately from general reports of adverse events as they were considered as adverse events of special interest.
 
Arm/Group Title Icatibant 30 mg Placebo
Hide Arm/Group Description Participants received a single dose of icatibant 30 mg SC injection within 12 hours after the onset of the ACE-I induced angioedema attack. Participants received a single dose of placebo matched to icatibant SC injection within 12 hours after the onset of the ACE-I induced angioedema attack.
All-Cause Mortality
Icatibant 30 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Icatibant 30 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/60 (3.33%)      1/58 (1.72%)    
Respiratory, thoracic and mediastinal disorders     
Hypoxia * 1  1/60 (1.67%)  1 0/58 (0.00%)  0
Laryngeal oedema * 1  1/60 (1.67%)  1 0/58 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash pruritic * 1  0/60 (0.00%)  0 1/58 (1.72%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Icatibant 30 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/60 (23.33%)      11/58 (18.97%)    
Gastrointestinal disorders     
Nausea * 1  0/60 (0.00%)  0 3/58 (5.17%)  3
Nervous system disorders     
Headache * 1  7/60 (11.67%)  7 4/58 (6.90%)  4
Respiratory, thoracic and mediastinal disorders     
Dysphonia * 1  3/60 (5.00%)  4 2/58 (3.45%)  2
Dyspnoea * 1  1/60 (1.67%)  1 3/58 (5.17%)  3
Skin and subcutaneous tissue disorders     
Angioedema * 1  7/60 (11.67%)  9 2/58 (3.45%)  4
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
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.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Physician
Organization: Shire
Phone: 1 866-842-5335
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01919801     History of Changes
Other Study ID Numbers: HGT-FIR-096
2014-001213-12 ( EudraCT Number )
First Submitted: July 25, 2013
First Posted: August 9, 2013
Results First Submitted: August 16, 2016
Results First Posted: October 10, 2016
Last Update Posted: December 13, 2018