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

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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

Tracking Information
First Submitted Date  ICMJE July 12, 2007
First Posted Date  ICMJE July 13, 2007
Results First Submitted Date  ICMJE October 30, 2013
Results First Posted Date  ICMJE June 9, 2014
Last Update Posted Date February 16, 2015
Study Start Date  ICMJE March 2005
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2014)
Time to Onset of Symptom Relief. [ Time Frame: 2 days ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 12, 2007)
Symptom relief (patient)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2014)
Time to Almost Complete Symptom Relief [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2007)
Safety and tolerability Additional efficacy assessments Pharmacoeconomics
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE)
Official Title  ICMJE Randomised Double Blind, Controlled, Parallel Group, Multicentre Study of a Subcutaneous Formulation of Icatibant Versus Oral Tranexamic Acid for the Treatment of Hereditary Angioedema (HAE)
Brief Summary

Primary Outcome Measures:

The primary endpoint was the time to onset of symptom relief of the first attack in the double blind phase. H0: λ icatibant/λ tranexamic acid =1 versus H1: λ icatibant/λ tranexamic acid ≠1 Where: λ icatibant refers to the hazard rate under icatibant and λ tranexamic acid refers to the hazard rate under tranexamic acid.

Secondary Outcome Measures:

  • Additional efficacy assessments (Time to Almost Complete Symptom Relief)
  • Safety and tolerability
  • Pharmacoeconomics
Detailed Description

This was a Phase III, randomised, double blind, double dummy, multicentre, controlled,parallel group study of a 30 mg s.c. formulation of icatibant for the treatment of patients with moderate to very severe symptoms of cutaneous and/or abdominal symptoms of HAE.

The study consisted of two parts: controlled phase and OLE phase. For the primary endpoint, Efficacy was determined by evaluating the differences in study outcomes using a Visual Analogue Scale for patients treated with icatibant and tranexamic acid.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hereditary Angioedema
Intervention  ICMJE
  • Drug: Icatibant
    Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.
    Other Name: Brand name, Firazyr®
  • Drug: Tranexamic Acid
    over encapsulated film tablet an anti-fibrinolytic agent,is used in some European countries for the treatment of acute oedema episodes and the continuous prophylaxis of HAE.
  • Drug: Oral Placebo
    hard capsule matched to tranexamic acid
    Other Name: Placebo
  • Drug: S.C. Placebo
    solution for injection, matched to icatibant for injection
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: Randomized controlled -Icatibant

    Subjects received S.C icatibant+ oral placebo

    Icatibant Form: solution for injection, 3 mL, 10 mg/mL Single dose: 30 mg (3 mL)

    Placebo Form: hard capsule Single dose: 2 capsules Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart

    Interventions:
    • Drug: Icatibant
    • Drug: Oral Placebo
  • Active Comparator: Randomized controlled-Tranexamic acid

    Subjects received oral Tranexamic acid+ S.C. placebo

    Tranexamic acid Form: over encapsulated film tablet Single dose: 1000 mg (2 capsules) Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart

    Placebo Form: solution for injection, matched to icatibant for injection Single dose: 3 mL Frequency: one subcutaneous injection in the abdominal region

    Interventions:
    • Drug: Tranexamic Acid
    • Drug: S.C. Placebo
  • Experimental: 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.
    Intervention: Drug: Icatibant
  • Experimental: 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
    Intervention: Drug: Icatibant
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 20, 2014)
85
Original Actual Enrollment  ICMJE
 (submitted: July 12, 2007)
80
Actual Study Completion Date  ICMJE March 2008
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age above 18 years;
  • Documented diagnosis of HAE Type I or II (confirmed C1-INH deficiency);
  • Current edema in the cutaneous, abdominal and/or laryngeal areas;
  • Current edema moderate to severe according to the investigator's Symptom Score.

Exclusion Criteria:

  • Diagnosis of angioedema other than HAE,
  • Participation in a clinical trial of another investigational medicinal product (IMP)within the past month
  • Treatment with any pain medication since onset of the current angioedema attack
  • Treatment with replacement therapy, including C1-INH products, less than 3 days before onset of the current angioedema attack
  • Treatment with Tranexamic acid replacement therapy within a week before onset of the current angioedema attack
  • Treatment with ACE inhibitors
  • Contraindications for Tranexamic acid
  • Evidence of coronary artery disease based on medical history or Screening examination in particular unstable angina pectoris or severe coronary heart disease
  • Congestive heart failure (class 3 and 4)
  • Serum creatinine level of ≥ 250 μmol/L
  • Serious concomitant illness that the investigator considered to be a contraindication for participation in the trial
  • Pregnancy (as assessed prior to treatment) and/or breast-feeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00500656
Other Study ID Numbers  ICMJE JE049 #2102
2004-001540-71 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shire
Study Sponsor  ICMJE Shire
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marco Cicardi, Prof. Dr. University of Milan
PRS Account Shire
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP