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
  Purpose

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

Condition Intervention Phase
Hereditary Angioedema
Drug: Icatibant
Drug: Tranexamic Acid
Drug: Oral Placebo
Drug: S.C. Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.


Enrollment: 85
Study Start Date: March 2005
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Drug: Icatibant
Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.
Other Name: Brand name, Firazyr®
Drug: Oral Placebo
hard capsule matched to tranexamic acid
Other Name: 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

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: S.C. Placebo
solution for injection, matched to icatibant for injection
Other Name: 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.
Drug: Icatibant
Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.
Other Name: Brand name, Firazyr®
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
Drug: Icatibant
Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.
Other Name: Brand name, Firazyr®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00500656

Locations
Italy
Università degli Studi di Milano, Dipartimento di Medicina Interna
Milano, Italy, 20123
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Marco Cicardi, Prof. Dr. University of Milan
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00500656     History of Changes
Other Study ID Numbers: JE049 #2102
Study First Received: July 12, 2007
Results First Received: October 30, 2013
Last Updated: June 25, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Additional relevant MeSH terms:
Angioedemas, Hereditary
Angioedema
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, Inborn
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Tranexamic Acid
Icatibant
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on September 16, 2014