Clinical trial NCT00500656: Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-07-13
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Time to Onset of Symptom Relief.
timeFrame: 2 days
Secondary outcomes:
measure: Time to Almost Complete Symptom Relief
timeFrame: 48 hours
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Università degli Studi di Milano, Dipartimento di Medicina Interna
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Bas M, Bier H, Greve J, Kojda G, Hoffmann TK. Novel pharmacotherapy of acute hereditary angioedema with bradykinin B2-receptor antagonist icatibant. Allergy. 2006 Dec;61(12):1490-2. doi: 10.1111/j.1398-9995.2006.01197.x. No abstract available.
citation: Bas M, Greve J, Hoffmann TK, Reshef A, Aberer W, Maurer M, Kivity S, Farkas H, Floccard B, Arcoleo F, Martin L, Sitkauskiene B, Bouillet L, Schmid-Grendelmeier P, Li H, Zanichelli A. Repeat treatment with icatibant for multiple hereditary angioedema attacks: FAST-2 open-label study. Allergy. 2013 Nov;68(11):1452-9. doi: 10.1111/all.12244. Epub 2013 Sep 21.
citation: Cicardi M, Banerji A, Bracho F, Malbran A, Rosenkranz B, Riedl M, Bork K, Lumry W, Aberer W, Bier H, Bas M, Greve J, Hoffmann TK, Farkas H, Reshef A, Ritchie B, Yang W, Grabbe J, Kivity S, Kreuz W, Levy RJ, Luger T, Obtulowicz K, Schmid-Grendelmeier P, Bull C, Sitkauskiene B, Smith WB, Toubi E, Werner S, Anne S, Bjorkander J, Bouillet L, Cillari E, Hurewitz D, Jacobson KW, Katelaris CH, Maurer M, Merk H, Bernstein JA, Feighery C, Floccard B, Gleich G, Hebert J, Kaatz M, Keith P, Kirkpatrick CH, Langton D, Martin L, Pichler C, Resnick D, Wombolt D, Fernandez Romero DS, Zanichelli A, Arcoleo F, Knolle J, Kravec I, Dong L, Zimmermann J, Rosen K, Fan WT. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):532-41. doi: 10.1056/NEJMoa0906393.