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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00500656
First received: July 12, 2007
Last updated: June 25, 2014
Last verified: May 2014

July 12, 2007
June 25, 2014
March 2005
March 2008   (final data collection date for primary outcome measure)
Time to Onset of Symptom Relief. [ Time Frame: 2 days ] [ Designated as safety issue: No ]

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.

Symptom relief (patient)
Complete list of historical versions of study NCT00500656 on ClinicalTrials.gov Archive Site
Time to Almost Complete Symptom Relief [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
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.
Safety and tolerability Additional efficacy assessments Pharmacoeconomics
Not Provided
Not Provided
 
Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE)
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)

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hereditary Angioedema
  • 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
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
85
March 2008
March 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
NCT00500656
JE049 #2102
Yes
Shire
Shire
Not Provided
Principal Investigator: Marco Cicardi, Prof. Dr. University of Milan
Shire
May 2014

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