Page last updated: 2024-11-11

icatibant

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

icatibant: a potent bradykinin (B2) receptor antagonist; WIN 65365 is an L-Tic(7) stereoisomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

icatibant : A ten-membered synthetic oligopeptide consisting of D-Arg, Arg, Pro, Hyp, Gly, Thi, Ser, D-Tic, Oic, and Arg residues joined in sequrence. A bradykinin receptor antagonist used as its acetate salt for the treatment of acute attacks of hereditary angioedema in adult patients. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID6918173
CHEMBL ID2028850
SCHEMBL ID21495177
MeSH IDM0180524
PubMed CID14724482
SCHEMBL ID15992446
MeSH IDM0180524

Synonyms (42)

Synonym
l-arginine, d-arginyl-l-arginyl-l-prolyl-trans-4-hydroxy-l-prolylglycyl-3-(2-thienyl)-l-alanyl-l-seryl-d-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-l-(2alpha,3abeta,7abeta)-octahydro-1h-indole-2-carbonyl-
icatibant [inn]
je 049
DB06196
CHEMBL2028850
7pg89g35q7 ,
unii-7pg89g35q7
icatibant [inn:ban]
bdbm50403371
bdbm50406750
icatibant [who-dd]
(r)-arginyl-(s)-arginyl-(s)-prolyl-(2s,4r)-(4-hydroxyprolyl)glycyl-(s)-(3-(2-thienyl)alanyl)-(s)-seryl-(r)-((1,2,3,4-tetrahydro-3-isoquinolyl)carbonyl)-(2s,3as,7as)-((hexahydro-2-indolinyl)carbonyl)-(s)-arginine
icatibant [mi]
l-arginine, d-arginyl-l-arginyl-l-prolyl-trans-4-hydroxy-l-prolylglycyl-3-(2-thienyl)-l-alanyl-l-seryl-d-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-l-(2.alpha.,3a.beta.,7a.beta.)-octahydro-1h-indole-2-carbonyl-
icatibant [ema epar]
icatibant [vandf]
HY-17446
CS-3381
hoe 140, >=94%
hoe-140 (icatibant)
SCHEMBL21495177
DTXSID20903963 ,
Q902379
icatibant-acetate
NCGC00390805-02
icatibant hoe 140
AT24149
EN300-18166877
b06ac02
d-arg-(hyp3,thi5,d-tic7,oic8)bk
dtxcid901331902
icatibantum
icatibanto
AKOS040741862
firazyr
icatibant
130308-48-4
L001394
SCHEMBL15992446
hoe 140 acetate
BCP19031
hoe140; hoe 140; hoe-140;icatibant acetate(138614-30-9)

Research Excerpts

Toxicity

Our working hypothesis is that treatment with standard of care-plus-icatibant is effective and safe to treat patients infected with SARS-CoV-2. We treated a pregnant nC1-INH HAE patient, with no adverse effects or abnormalities, to add to the growing knowledge of icatibants use during pregnancy.

ExcerptReferenceRelevance
" The only adverse events were mild, spontaneously resolving injection site reactions."( Safety and efficacy of icatibant self-administration for acute hereditary angioedema.
Boccon-Gibod, I; Bouillet, L, 2012
)
0.38
"6%) did not report adverse events (AEs)."( Long-term safety of icatibant treatment of patients with angioedema in real-world clinical practice.
Aberer, W; Andresen, I; Bouillet, L; Caballero, T; Fabien, V; Longhurst, HJ; Maurer, M; Zanichelli, A, 2017
)
0.46
" Thirty-two treatment-emergent adverse events (all mild or moderate) occurred in 9 (28."( Treatment Effect and Safety of Icatibant in Pediatric Patients with Hereditary Angioedema.
Aberer, W; Bernstein, JA; Caballero, T; Farkas, H; Hao, J; Li, HH; McCarthy, L; Nothaft, W; Reshef, A; Schranz, J,
)
0.13
" There were 3 patients who experienced 3 adverse events (2 HAE attacks and 1 headache); 7 patients experienced an injection site reaction."( [EFFICACY, PHARMACOKINETICS, AND SAFETY OF ICATIBANT FOR THE TREATMENT OF JAPANESE PATIENTS WITH AN ACUTE ATTACK OF HEREDITARY ANGIOEDEMA: A PHASE 3 OPEN-LABEL STUDY].
Eto, K; Fukunaga, A; Hao, J; Hide, M; Maehara, J; Nomoto, Y; Vardi, M,
)
0.13
" Seven patients experienced an injection site reaction, and 3 patients had adverse events (2 patients had a worsening or repeat HAE attack 29."( Efficacy, pharmacokinetics, and safety of icatibant for the treatment of Japanese patients with an acute attack of hereditary angioedema: A phase 3 open-label study.
Eto, K; Fukunaga, A; Hao, J; Hide, M; Maehara, J; Nomoto, Y; Vardi, M, 2020
)
0.56
"Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough."( Evaluation of the efficacy and safety of icatibant and C1 esterase/kallikrein inhibitor in severe COVID-19: study protocol for a three-armed randomized controlled trial.
Araujo, EP; Benaglia, T; Bernardes, AF; Bombassaro, B; Bueno, FF; de Lima-Júnior, JC; Dertkigil, RP; Dertkigil, SS; Falcão, ALE; Maia, RP; Mansour, E; Monfort-Pires, M; Moretti, ML; Nunes, TA; Palma, A; Ribeiro, LC; Santos, TM; Trabasso, P; Ulaf, RG; Velloso, LA, 2021
)
0.62
" Our working hypothesis is that treatment with standard of care-plus-icatibant is effective and safe to treat patients infected with SARS-CoV-2 admitted to hospital for pneumonia without invasive mechanical ventilation."( A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study pr
Carnaval, T; Fernández-Nistal, A; Giol, J; Lleonart, R; Malchair, P; Montoto, C; Otero, A; Sánchez-Gabriel, A; Solanich, X; Videla, S, 2022
)
0.72
"Our experience of treating a pregnant nC1-INH HAE patient with icatibant is presented, with no adverse effects or abnormalities, to add to the growing knowledge of icatibant use during pregnancy."( Is Icatibant Safe for the Treatment of Hereditary Angioedema During Pregnancy?
Novak, S; Šimac, DV; Štimac, T, 2022
)
0.72
" Mild or moderate injection-site reactions were the only adverse events reported."( Safety, efficacy, and pharmacokinetics of icatibant treatment in Japanese pediatric patients with hereditary angioedema: A phase 3, open-label study.
Dote, N; Hide, M; Ishida, K; Miyakawa, K; Sugiura, K; Wang, Y, 2023
)
0.91

Pharmacokinetics

Icatibant was rapidly absorbed, with a pharmacokinetic profile consistent with previous studies. The total plasma icatibant exposure for the 30- and 90-mg doses was 6,736 ± 1,230 h · ng/mL.

ExcerptReferenceRelevance
" To-date, no thorough investigation of the clinical pharmacokinetic (PK) parameters of icatibant and its primary metabolites has been reported."( Pharmacokinetics of single and repeat doses of icatibant.
Leach, JK; Mascelli, M; McCauley, TG; Spencer, K, 2015
)
0.42
" Icatibant was rapidly absorbed, with a pharmacokinetic profile consistent with previous studies."( Safety, efficacy, and pharmacokinetics of icatibant treatment in Japanese pediatric patients with hereditary angioedema: A phase 3, open-label study.
Dote, N; Hide, M; Ishida, K; Miyakawa, K; Sugiura, K; Wang, Y, 2023
)
0.91

Compound-Compound Interactions

ExcerptReferenceRelevance
" We wished to determine the cardioprotective actions of an aminopeptidase P inhibitor, apstatin alone and in combination with enalapril/lisinopril/ramipril in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h)."( Infarct size limiting effect of apstatin alone and in combination with enalapril, lisinopril and ramipril in rats with experimental myocardial infarction.
Akula, A; Kota, MK; Routhu, KV; Veeravalli, KK, 2003
)
0.32

Bioavailability

ExcerptReferenceRelevance
" ACEI decreased ANG II production but also increased bradykinin bioavailability by reducing its degradation."( ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats.
Allard, J; Buléon, M; Cellier, E; Conti, M; Girolami, JP; Pecher, C; Praddaude, F; Renaud, I; Tack, I, 2007
)
0.34

Dosage Studied

No reports have been published to date on multiple dosing with icatibant during the first trimester of pregnancy. Kinase II inhibitor captopril or exogenous bradykinin resulted in microcirculatory stasis, extensive venular leukocyte adherence, and severe histological damage.

ExcerptRelevanceReference
" The dose-response curve to acrolein was also significantly inhibited by treatment with indomethacin (10 microM) and slightly affected by Hoe 140 (1 microM)."( Characterization of the capsaicin-sensitive component of cyclophosphamide-induced inflammation in the rat urinary bladder.
Ahluwalia, A; Giuliani, S; Lecci, A; Maggi, CA; Santicioli, P, 1994
)
0.29
"0 mg per site), whereas the dose-response curves obtained by bradykinin (1-100 nmol per site), platelet-activating factor (0."( Involvement of bradykinin in endotoxin-induced vascular permeability increase in the skin of rats.
Naraba, H; Oh-ishi, S; Tokumasu, T; Ueno, A, 1995
)
0.29
" In further experiments we determined the time course and the minimal dosage required for the induction of this severe and non-invasive disease variety."( Characterization of a non-invasive, vascular model of acute necrotizing pancreatitis.
Adler, G; Gress, TM; Lerch, MM; Schoenberg, MH; Turi, S; Weidenbach, H, 1996
)
0.29
" Bk reduced the size of the pressor responses at relatively low concentrations (2-60 nM) but the dose-response curve was flat and the maximum inhibitory effect hardly exceeded 50 percent."( Comparison of the vasodilatory effects of bradykinin in isolated dog renal arteries and in buffer-perfused dog kidneys.
Hadházy, P; Koltai, MZ; Malomvölgyi, B; Pogátsa, G; Tekes, K, 1996
)
0.29
" Des-Arg9-bradykinin-mediated contractions were inhibited by the specific bradykinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin which produced parallel shifts in the dose-response curve to the selective bradykinin B1 receptor agonist."( Bradykinin B1 receptors in human umbilical vein.
Antúnez, P; Pérez, H; Rothlin, RP; Sardi, SP, 1997
)
0.3
" Kinase II inhibitor captopril or exogenous bradykinin in addition to an otherwise effective dosage of icatibant resulted in microcirculatory stasis, extensive venular leukocyte adherence, and severe histological damage."( Inhibition of bradykinin B2 receptor preserves microcirculation in experimental pancreatitis in rats.
Bloechle, C; Izbicki, JR; Knoefel, WT; Kuehn, RM; Kusterer, K; Schneider, C, 1998
)
0.3
" Hoe 140, dose-dependently shifted the dose-response curves of bradykinin to the right, whereas the bradykinin B1 receptor antagonist, des-Arg10-[Leu9]-kallidin proved ineffective."( Positive chronotropic activity of bradykinin in the pithed normotensive rat.
Loro, JF; Pfaffendorf, M; van Zwieten, PA; Zhang, J, 1998
)
0.3
" However, when animals were pre-treated with BCG, the dose-response curves for both B1 agonists were shifted 2 to 8-fold to the left."( Systemic treatment with Mycobacterium bovis bacillus Calmette-Guérin (BCG) potentiates kinin B1 receptor agonist-induced nociception and oedema formation in the formalin test in mice.
Calixto, JB; de Campos, RO; Henriques, MG, 1998
)
0.3
" Mean arterial pressure (MAP), heart rate (HR), and renal blood flow (RBF) were recorded from conscious unrestrained rats while five-point cumulative dose-response curves were constructed during infusion or bolus injection of BK (5-80 microg kg(-1))."( Bradykinin B2-receptors mediate the pressor and renal hemodynamic effects of intravenous bradykinin in conscious rats.
Hoagland, KM; Maddox, DA; Martin, DS, 1999
)
0.3
" In two treatment groups, Icatibant was administered either in a low (100 nmol/kg BW; group 2, n = 10) or in a high dosage (5000 nmol/kg BW; group 3, n = 10)."( Bradykinin B2-receptor antagonism attenuates fatal cardiocirculatory breakdown induced by severe experimental pancreatitis.
Bloechle, C; Fink, E; Gippner-Steppert, C; Izbicki, JR; Jochum, M; Knoefel, WT; Scholz, J; Treede, H; Yekebas, E, 2000
)
0.31
"Angiotensin I-converting enzyme (ACE/kininase II) inhibitors potentiated guinea pig ileum's isotonic contractions to bradykinin (BK) and its analogues, shifting the BK dose-response curve to the left."( Potentiation of the effects of bradykinin on its receptor in the isolated guinea pig ileum.
Erdös, EG; Igić, R; Minshall, RD; Nedumgottil, SJ; Rabito, SF, 2000
)
0.31
" Disease control, quality of life, adverse events, and administered dosage per month were compared for 6 months on on-demand therapy and the following 6 months under prophylactic therapy."( Nanofiltrated C1-esterase-inhibitor in the prophylactic treatment of bradykinin-mediated angioedema.
Bas, M; Buchberger, M; Greve, J; Hahn, J; Hajdu, Z; Hoffmann, TK; Nordmann, M; Schuler, PJ; Strassen, U, 2016
)
0.43
" No reports have been published to date on multiple dosing with icatibant during the first trimester of pregnancy."( First report of icatibant treatment in a pregnant patient with hereditary angioedema.
Farkas, H; Kőhalmi, KV; Tóth, F; Varga, L; Veszeli, N, 2016
)
0.43
" FFP has limited evidence demonstrating a benefit for treatment of ACEI-induced angioedema without consistent dosing strategies."( Novel Therapies for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review of Current Evidence.
Riha, HM; Rivera, JV; Summers, BB; Van Berkel, MA, 2017
)
0.46
" However, observed treatment behaviours suggest patterns of suboptimal dosing for pdC1-INH."( Costs and effects of on-demand treatment of hereditary angioedema in Italy: a prospective cohort study of 167 patients.
Borsoi, L; Cicardi, M; Crosta, V; Federici, C; Gidaro, A; Perego, F; Tarricone, R; Zanichelli, A, 2018
)
0.48
" Treatment behaviours and suboptimal dosing of pdC1-INH may account for the differences, but further research is needed to define their role."( Costs and effects of on-demand treatment of hereditary angioedema in Italy: a prospective cohort study of 167 patients.
Borsoi, L; Cicardi, M; Crosta, V; Federici, C; Gidaro, A; Perego, F; Tarricone, R; Zanichelli, A, 2018
)
0.48
" We have detected an impurity with a high structural similarity to icatibant in pharmaceutical dosage forms using an optimized chromatographic method based on reversed phase high performance liquid chromatography with UV detection."( The identification and chromatographic separation of a new highly analogous impurity of the active pharmaceutical ingredient icatibant.
Fasshold, L; Goessler, W; Lajin, B; Steiner, O; Zangger, K, 2019
)
0.51
" A population modeling and simulation approach was used to examine sources of variability impacting icatibant pharmacokinetics (PK) and provide guidance on icatibant dosing in pediatric patients with HAE."( Population Pharmacokinetics and Exposure-Response Analyses to Guide Dosing of Icatibant in Pediatric Patients With Hereditary Angioedema.
Jomphe, C; Marier, JF; Martin, P; Wang, Y, 2021
)
0.62
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
peptidomimeticA small protein-like chain designed to mimic a peptide.
beta-adrenergic antagonistAn agent that binds to but does not activate beta-adrenergic receptors thereby blocking the actions of endogenous or exogenous beta-adrenergic agonists. beta-Adrenergic antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches and anxiety.
bradykinin receptor antagonistAn antagonist at the bradykinin receptor.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
oligopeptideA peptide containing a relatively small number of amino acids.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (10)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
B2 bradykinin receptorCavia porcellus (domestic guinea pig)IC50 (µMol)0.00250.00112.58648.0000AID43134; AID43135
Gamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)Ki0.00010.00010.04380.1630AID43306
Gamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)Ki0.00010.00010.04380.1630AID43306
Gamma-aminobutyric acid receptor subunit alpha-2Bos taurus (cattle)Ki0.00010.00010.04530.1630AID43306
Gamma-aminobutyric acid receptor subunit alpha-3Bos taurus (cattle)Ki0.00010.00010.04530.1630AID43306
5-hydroxytryptamine receptor 1ARattus norvegicus (Norway rat)IC50 (µMol)0.00050.00031.38338.4000AID43156
Gamma-aminobutyric acid receptor subunit alpha-4Bos taurus (cattle)Ki0.00010.00010.04530.1630AID43306
Gamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)Ki0.00010.00010.04530.1630AID43306
B2 bradykinin receptorRattus norvegicus (Norway rat)Ki0.00010.00010.00030.0005AID43306
B2 bradykinin receptorHomo sapiens (human)IC50 (µMol)0.00190.00040.02120.2800AID43150; AID43152; AID43153; AID43156
B2 bradykinin receptorHomo sapiens (human)Ki0.00010.00000.70577.6740AID263934; AID43145; AID43286; AID43290
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
B2 bradykinin receptorHomo sapiens (human)Kd0.00030.00030.00030.0003AID263935
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (21)

Processvia Protein(s)Taxonomy
inhibitory synapse assemblyGamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)
monoatomic ion transportGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
gamma-aminobutyric acid signaling pathwayGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
cellular response to histamineGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
inhibitory synapse assemblyGamma-aminobutyric acid receptor subunit alpha-2Bos taurus (cattle)
cellular response to histamineGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
chloride transmembrane transportGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
inhibitory synapse assemblyGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
smooth muscle contractionB2 bradykinin receptorHomo sapiens (human)
inflammatory responseB2 bradykinin receptorHomo sapiens (human)
cell surface receptor signaling pathwayB2 bradykinin receptorHomo sapiens (human)
cell surface receptor protein tyrosine kinase signaling pathwayB2 bradykinin receptorHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationB2 bradykinin receptorHomo sapiens (human)
blood circulationB2 bradykinin receptorHomo sapiens (human)
response to salt stressB2 bradykinin receptorHomo sapiens (human)
regulation of vasoconstrictionB2 bradykinin receptorHomo sapiens (human)
negative regulation of peptidyl-serine phosphorylationB2 bradykinin receptorHomo sapiens (human)
vasoconstrictionB2 bradykinin receptorHomo sapiens (human)
vasodilationB2 bradykinin receptorHomo sapiens (human)
regulation of vascular permeabilityB2 bradykinin receptorHomo sapiens (human)
arachidonic acid secretionB2 bradykinin receptorHomo sapiens (human)
negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediatorB2 bradykinin receptorHomo sapiens (human)
intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediatorB2 bradykinin receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayB2 bradykinin receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (10)

Processvia Protein(s)Taxonomy
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
ligand-gated monoatomic ion channel activityGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit alpha-3Bos taurus (cattle)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit alpha-3Bos taurus (cattle)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
chloride channel activityGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
protease bindingB2 bradykinin receptorHomo sapiens (human)
phosphatidylinositol phospholipase C activityB2 bradykinin receptorHomo sapiens (human)
bradykinin receptor activityB2 bradykinin receptorHomo sapiens (human)
protein bindingB2 bradykinin receptorHomo sapiens (human)
type 1 angiotensin receptor bindingB2 bradykinin receptorHomo sapiens (human)
protein heterodimerization activityB2 bradykinin receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (9)

Processvia Protein(s)Taxonomy
cytoplasmic vesicle membraneGamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)
postsynaptic specialization membraneGamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)
chloride channel complexGamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)
GABA-A receptor complexGamma-aminobutyric acid receptor subunit alpha-1Bos taurus (cattle)
plasma membraneGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
postsynaptic membraneGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
chloride channel complexGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
GABA-A receptor complexGamma-aminobutyric acid receptor subunit beta-1Bos taurus (cattle)
cytoplasmic vesicle membraneGamma-aminobutyric acid receptor subunit alpha-2Bos taurus (cattle)
postsynaptic membraneGamma-aminobutyric acid receptor subunit alpha-2Bos taurus (cattle)
chloride channel complexGamma-aminobutyric acid receptor subunit alpha-2Bos taurus (cattle)
postsynaptic membraneGamma-aminobutyric acid receptor subunit alpha-3Bos taurus (cattle)
chloride channel complexGamma-aminobutyric acid receptor subunit alpha-3Bos taurus (cattle)
postsynaptic membraneGamma-aminobutyric acid receptor subunit alpha-4Bos taurus (cattle)
chloride channel complexGamma-aminobutyric acid receptor subunit alpha-4Bos taurus (cattle)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
cytoplasmic vesicle membraneGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
postsynaptic specialization membraneGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
chloride channel complexGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
GABA-A receptor complexGamma-aminobutyric acid receptor subunit gamma-2Bos taurus (cattle)
endosomeB2 bradykinin receptorHomo sapiens (human)
Golgi apparatusB2 bradykinin receptorHomo sapiens (human)
plasma membraneB2 bradykinin receptorHomo sapiens (human)
intracellular membrane-bounded organelleB2 bradykinin receptorHomo sapiens (human)
plasma membraneB2 bradykinin receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (35)

Assay IDTitleYearJournalArticle
AID42982Binding affinity towards bradykinin receptor using [3H]BK as radioligand in guinea pig ileum1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID43152Concentration required to inhibit specific binding of [3H]BK at 1.2 nM to A-431 cells (human epidermoid carcinoma) which express Bradykinin receptor B2 by 50%.1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 2. Overcoming the species difference between guinea pig and man.
AID43129Concentration required to inhibit specific binding of [ 3H]BK (0.06 nM) to Bradykinin receptor B2 in guinea pig ileum membrane preparations by 50%.1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 3. Discovering bioisosteres of the imidazo[1,2-a] pyridine moiety.
AID195474Percent recovery was evaluated in rat1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID92584Ability of Compound (Agonist) to contract isolated human umbilical vein in presence of inhibitor.1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Synthesis and characterization of bradykinin B(2) receptor agonists containing constrained dipeptide mimics.
AID43135In vitro antagonistic activity for Bradykinin receptor B2 by guinea pig pulmonary artery assay.1995Journal of medicinal chemistry, Jul-21, Volume: 38, Issue:15
Technetium-99m-labeled HOE 140: a potential bradykinin B2 receptor imaging agent.
AID43290Binding affinity towards human cloned Bradykinin receptor B2 expressed in CHO cells by [3H]bradykinin displacement.1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Synthesis and characterization of bradykinin B(2) receptor agonists containing constrained dipeptide mimics.
AID42999In vitro Bradykinin receptor B1 antagonist activity in functional tissue within rabbit aorta1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID79543pA2 value against guinea pig ileum.1993Journal of medicinal chemistry, May-14, Volume: 36, Issue:10
NMR and computational evidence that high-affinity bradykinin receptor antagonists adopt C-terminal beta-turns.
AID77901Compound tested in vivo for inhibition of Bradykinin induced Bronchoconstriction in anaesthetized guinea pig; % Inhibition at 3.2 mg/Kg p.o.; NT=Not tested1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 2. Overcoming the species difference between guinea pig and man.
AID263934Binding affinity to human bradykinin B2 receptor transfected in CHO cells2006Bioorganic & medicinal chemistry letters, May-01, Volume: 16, Issue:9
Bradykinin antagonists modified with dipeptide mimetic beta-turn inducers.
AID43145Binding affinity towards Bradykinin receptor B2 in human S34 clone cells1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID196660Agonistic activity on rat uterus(RUT) in presence of inhibitors1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Design and synthesis of potent bradykinin agonists containing a benzothiazepine moiety.
AID263935Antagonist activity against bradykinin B2 receptor2006Bioorganic & medicinal chemistry letters, May-01, Volume: 16, Issue:9
Bradykinin antagonists modified with dipeptide mimetic beta-turn inducers.
AID462401Inhibition of bradykinin-induced Hartley guinea pig ileum contraction at 1 uM relative to control2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Synthesis and bradykinin inhibitory activity of novel non-peptide compounds, and evaluation of in vivo analgesic activity.
AID77895Compound tested in vivo for inhibition of Bradykinin induced Bronchoconstriction in anaesthetized guinea pig; % Inhibition at 1 mg/Kg p.o.; NT=Not tested1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 2. Overcoming the species difference between guinea pig and man.
AID43156In vitro inhibitory activity towards human bradykinin receptor B2 expressed in CHO cells using [3H]BK (1.0 nM) as a radioligand2004Journal of medicinal chemistry, Mar-25, Volume: 47, Issue:7
A new series of highly potent non-peptide bradykinin B2 receptor antagonists incorporating the 4-heteroarylquinoline framework. Improvement of aqueous solubility and new insights into species difference.
AID319401Inhibition of rat recombinant cathepsin S-induced hyperalgesia in naive Wistar rat at 50 nmol administered 30 mins before cathepsin S challenge2007Proceedings of the National Academy of Sciences of the United States of America, Jun-19, Volume: 104, Issue:25
Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain.
AID319405Inhibition of rat recombinant cathepsin S-induced hyperalgesia in Wistar rat at 50 ug2007Proceedings of the National Academy of Sciences of the United States of America, Jun-19, Volume: 104, Issue:25
Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain.
AID43150Inhibition specific binding of [3H]BK (1.0 nM) to human Bradykinin receptor B2 which was expressed in CHO (Chinese hamster ovary) cells by 50%.1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 3. Discovering bioisosteres of the imidazo[1,2-a] pyridine moiety.
AID78023Compound was evaluated for percentage inhibition against BK-induced bronchoconstriction in anesthetized guinea pig, intravenously at a concentration of 10 mg/kg2004Journal of medicinal chemistry, Mar-25, Volume: 47, Issue:7
A new series of highly potent non-peptide bradykinin B2 receptor antagonists incorporating the 4-heteroarylquinoline framework. Improvement of aqueous solubility and new insights into species difference.
AID43134In vitro antagonistic activity for Bradykinin receptor B2 by guinea pig ileal membrane receptor assay.1995Journal of medicinal chemistry, Jul-21, Volume: 38, Issue:15
Technetium-99m-labeled HOE 140: a potential bradykinin B2 receptor imaging agent.
AID77908Compound was evaluated for percentage inhibition against BK-induced bronchoconstriction in anesthetized guinea pig, intravenously at a concentration of 1 mg/kg2004Journal of medicinal chemistry, Mar-25, Volume: 47, Issue:7
A new series of highly potent non-peptide bradykinin B2 receptor antagonists incorporating the 4-heteroarylquinoline framework. Improvement of aqueous solubility and new insights into species difference.
AID24344In vitro stability was measured in rat kidney tissue preparation1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID43128Concentration required to inhibit specific binding of [3H]BK at 0.06 nM to Bradykinin receptor B2 in guinea pig ileum membrane preparations by 50%.1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 2. Overcoming the species difference between guinea pig and man.
AID43306Binding affinity against rat bradykinin B2 receptors expressed in CHO cells using [3H]bradykinin as radioligand1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Design and synthesis of potent bradykinin agonists containing a benzothiazepine moiety.
AID43153Concentration required to inhibit specific binding of [3H]BK (1.2 nM) to A-431 cells (human epidermoid carcinoma) which express Bradykinin receptor B2 by 50%.1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 3. Discovering bioisosteres of the imidazo[1,2-a] pyridine moiety.
AID43141In vitro binding affinity against bradykinin receptor B2 from guinea pig ileum.1993Journal of medicinal chemistry, May-14, Volume: 36, Issue:10
NMR and computational evidence that high-affinity bradykinin receptor antagonists adopt C-terminal beta-turns.
AID24343In vitro stability was measured in porcine lung tissue preparation1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID24342In vitro stability was measured in porcine kidney tissue preparation1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID24166In vitro stability was measured in human plasma tissue preparation1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID92585Agonistic activity on human umbilical vein(HUV) in presence of inhibitors1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Design and synthesis of potent bradykinin agonists containing a benzothiazepine moiety.
AID43309In vitro Bradykinin receptor B2 antagonist activity by using rat uterus functional assay1996Journal of medicinal chemistry, Mar-29, Volume: 39, Issue:7
Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.
AID43286Binding affinity against human cloned Bradykinin receptor B2 expressed in CHO cells using [3H]-bradykinin as radioligand1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Design and synthesis of potent bradykinin agonists containing a benzothiazepine moiety.
AID43136In vitro inhibitory activity towards bradykinin receptor B2 using [3H]BK (0.06 nM) as a radioligand in guinea pig ileum membrane preparation2004Journal of medicinal chemistry, Mar-25, Volume: 47, Issue:7
A new series of highly potent non-peptide bradykinin B2 receptor antagonists incorporating the 4-heteroarylquinoline framework. Improvement of aqueous solubility and new insights into species difference.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,090)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's494 (45.32)18.2507
2000's308 (28.26)29.6817
2010's245 (22.48)24.3611
2020's43 (3.94)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 68.63

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index68.63 (24.57)
Research Supply Index2.48 (2.92)
Research Growth Index4.27 (4.65)
Search Engine Demand Index112.21 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (68.63)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Trials49 (4.31%)5.53%
Reviews0 (0.00%)6.00%
Reviews95 (8.36%)6.00%
Case Studies0 (0.00%)4.05%
Case Studies57 (5.01%)4.05%
Observational0 (0.00%)0.25%
Observational19 (1.67%)0.25%
Other11 (100.00%)84.16%
Other917 (80.65%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (25)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Multicenter Study, Randomized, Double-blind With 2 Groups as Prove of Concept for the Treatment of ACEI Induced Angioedema With Subcutaneous Icatibant [NCT01154361]Phase 20 participants InterventionalCompleted
I-SPY COVID TRIAL: An Adaptive Platform Trial to Reduce Mortality and Ventilator Requirements for Critically Ill Patients [NCT04488081]Phase 21,500 participants (Anticipated)Interventional2020-07-31Recruiting
A Multicenter, Open-Label, Non-randomized Phase 3 Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneous Administration of Icatibant (TAK-667) in Japanese Children and Adolescents With Acute Attacks of Hereditary Angioedema [NCT04654351]Phase 32 participants (Actual)Interventional2021-01-15Completed
A Multicenter, Open-Label, Non-Randomized Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Single Subcutaneous Administration of Icatibant in Children and Adolescents With Hereditary Angioedema [NCT01386658]Phase 332 participants (Actual)Interventional2012-01-27Completed
Prospective, Randomised, Double-blind Trial of Icatibant Compared to Placebo in Patients With Early Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infection [NCT05407597]Phase 2/Phase 332 participants (Actual)Interventional2022-05-16Completed
Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad-Cov Study). [NCT05010876]Phase 244 participants (Actual)Interventional2021-02-04Completed
Specified Drug Use Surveillance of FIRAZYR Subcutaneous Injection 30mg Syringe for Pediatric Subjects With Hereditary Angioedema (All-Case Investigation) [NCT05509569]10 participants (Anticipated)Observational2022-08-24Recruiting
Efficacy and Safety of Intra-articular Multiple Doses of 500 µg Icatibant Including 40 mg Triamcinolone as Calibrator in a Randomized, Double-blind, Parallel-group, Placebo-controlled 13-week Multi-centre Study in Patients With Symptomatic Knee Osteoarthr [NCT00303056]Phase 2590 participants (Actual)Interventional2006-02-28Completed
A Phase III Randomized, Double-Blind,Placebo-Controlled, Multicenter Study of Icatibant for Subcutaneous Injection in Patients With Acute Attacks of Hereditary Angioedema (HAE) [NCT00912093]Phase 398 participants (Actual)Interventional2009-07-16Completed
Mitochondrial Dysfunction in Chronic Kidney Disease [NCT03177798]Phase 211 participants (Actual)Interventional2017-08-01Completed
Bradykinin Receptor Antagonism During Cardiopulmonary Bypass [NCT00223704]Phase 2/Phase 3150 participants (Actual)Interventional2006-05-31Completed
Mechanism(s) Underlying Cardiovascular Effects of ARB/NEP Inhibition - Aim 2 [NCT03005184]Phase 20 participants (Actual)Interventional2017-09-30Withdrawn(stopped due to Study is being redesigned and submitted as a new study.)
Open Label, Multicenter Study to Evaluate Efficacy, Safety and Tolerability of a Self-Administered Subcutaneous Formulation of Icatibant for the Treatment of Acute Attacks of Hereditary Angioedema (IHA) [NCT01457430]Phase 419 participants (Actual)Interventional2011-12-31Completed
Study of a Bradykinin Receptor Blocker in Angiotensin Converting Enzyme Inhibitor-Associated Angioedema [NCT00517582]Phase 113 participants (Actual)Interventional2007-09-30Terminated(stopped due to This study was stopped to allow initiation of a mult-center study)
Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study Evaluating the Safety & Efficacy of Icatibant as a Treatment for Angiotensin-Converting Enzyme Inhibitor (ACE-I)-Induced Angioedema in Adults [NCT01919801]Phase 3118 participants (Actual)Interventional2013-12-02Completed
Mechanisms Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 2 [NCT04113109]Phase 480 participants (Anticipated)Interventional2019-11-01Recruiting
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) [NCT00500656]Phase 385 participants (Actual)Interventional2005-03-01Completed
Open Label, Multicenter Study to Evaluate Safety, Local Tolerability, Convenience, and Efficacy of a Self-Administered Subcutaneous Formulation of Icatibant for the Treatment of Acute Attacks of Hereditary Angioedema [NCT00997204]Phase 3151 participants (Actual)Interventional2009-09-25Completed
Randomized, Open, Multicenter Phase II Clinical Trial, Proof of Concept, to Evaluate Efficacy and Safety of Icatibant in Hospitalized Patients With SARS-COV-2 (COVID-19) Without Assisted Ventilation Compared With Standard Care [NCT04978051]Phase 273 participants (Actual)Interventional2021-04-12Completed
Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema - a Mulitcenter Trial [NCT01574248]Phase 433 participants (Actual)Interventional2011-08-31Terminated(stopped due to DSMC recommended discontinuation for futility and feasibility)
An Open-Label Study of Icatibant in Japanese Subjects With Acute Attacks of Hereditary Angioedema. [NCT03888755]Phase 38 participants (Actual)Interventional2015-03-18Completed
An Open-label, Single-arm Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Single Subcutaneous Dose of Icatibant in Healthy Japanese Volunteers [NCT02045264]Phase 112 participants (Actual)Interventional2014-02-21Completed
FIRAZYR General Drug Use-Results Survey (Japan) [NCT04057131]304 participants (Actual)Observational2019-05-09Active, not recruiting
Prevention of Intradialytic Hypotension by Inhibiting Bradykinin B2 Receptor A Randomized, Double-blind, Placebo-controlled, Cross Over Explorative Study [NCT05834777]Phase 326 participants (Anticipated)Interventional2023-12-11Recruiting
Randomized, Double Blind, Placebo-Controlled, Multicenter Study of a Subcutaneous Formulation of Icatibant for the Treatment of Hereditary Angioedema [NCT00097695]Phase 384 participants (Actual)Interventional2004-12-28Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00097695 (3) [back to overview]Time to Regression (Start of Improvement) According to Patient
NCT00097695 (3) [back to overview]Time to Onset of Symptom Relief (TOSR)
NCT00097695 (3) [back to overview]Time to Almost Complete Symptom Relief
NCT00223704 (5) [back to overview]Inflammatory Response as Measured by Interleukin-6
NCT00223704 (5) [back to overview]Fibrinolytic Response as Measured by D-dimer
NCT00223704 (5) [back to overview]Allogenic Blood Product Transfusion Risk
NCT00223704 (5) [back to overview]Units of Plasma Transfused During Hospitalization
NCT00223704 (5) [back to overview]Units of Packed Red Blood Cells Transfused During Hospitalization
NCT00500656 (2) [back to overview]Time to Almost Complete Symptom Relief
NCT00500656 (2) [back to overview]Time to Onset of Symptom Relief.
NCT00912093 (5) [back to overview]Time to Almost Complete Symptom Relief
NCT00912093 (5) [back to overview]Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient
NCT00912093 (5) [back to overview]Time to Subject-Assessed Initial Symptom Improvement
NCT00912093 (5) [back to overview]Time to Onset of Primary Symptom Relief
NCT00912093 (5) [back to overview]Time to Investigator-Assessed Initial Symptom Improvement
NCT00997204 (2) [back to overview]Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant
NCT00997204 (2) [back to overview]Clinical Efficacy of Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant, Time to Symptom Relief Using VAS Score for a Single Primary Symptom by Patient Cohort
NCT01386658 (29) [back to overview]Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3
NCT01386658 (29) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant
NCT01386658 (29) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant
NCT01386658 (29) [back to overview]Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant
NCT01386658 (29) [back to overview]Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant
NCT01386658 (29) [back to overview]Number of Participants Who Reported Presence of Anti-icatibant Antibodies
NCT01386658 (29) [back to overview]Number of Participants With Adverse Events (AEs)
NCT01386658 (29) [back to overview]Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations
NCT01386658 (29) [back to overview]Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs)
NCT01386658 (29) [back to overview]Number of Participants With Clinically Significant Changes in Reproductive Hormones
NCT01386658 (29) [back to overview]Number of Participants With Clinically Significant Changes in Vital Signs
NCT01386658 (29) [back to overview]Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1
NCT01386658 (29) [back to overview]Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
NCT01386658 (29) [back to overview]Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
NCT01386658 (29) [back to overview]Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1
NCT01386658 (29) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant
NCT01386658 (29) [back to overview]Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant
NCT01386658 (29) [back to overview]Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration
NCT01386658 (29) [back to overview]Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant
NCT01386658 (29) [back to overview]Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant
NCT01386658 (29) [back to overview]Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1
NCT01386658 (29) [back to overview]Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3
NCT01386658 (29) [back to overview]Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1
NCT01386658 (29) [back to overview]Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3
NCT01386658 (29) [back to overview]Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3
NCT01386658 (29) [back to overview]Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3
NCT01386658 (29) [back to overview]Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3
NCT01386658 (29) [back to overview]Time to Onset of Symptom Relief (TOSR) for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores
NCT01386658 (29) [back to overview]Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores
NCT01457430 (2) [back to overview]Time to Complete or Near Complete Resolution From Onset of Symptoms
NCT01457430 (2) [back to overview]Percent Change in VAS Scores
NCT01574248 (7) [back to overview]Number of Participants Given Steroids
NCT01574248 (7) [back to overview]Number of Participants With Admission to Intensive Care Unit
NCT01574248 (7) [back to overview]Number of Participants With Requirement for Intubation
NCT01574248 (7) [back to overview]Systolic Blood Pressure
NCT01574248 (7) [back to overview]Time to Resolution of Angioedema
NCT01574248 (7) [back to overview]Number of Participants Given Epinephrine
NCT01574248 (7) [back to overview]Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers
NCT01919801 (10) [back to overview]Number of Participants Experienced ACE-I-induced Angioedema Attack Following Study Drug Administration
NCT01919801 (10) [back to overview]Number of Participants Experienced Airway Intervention Due to ACE-I-induced Angioedema
NCT01919801 (10) [back to overview]Number of Participants With Clinically Significant Changes in Laboratory Evaluation, Vital Signs, Electrocardiogram (ECG) and Physical Examination
NCT01919801 (10) [back to overview]Time to Meeting Discharge Criteria (TMDC)
NCT01919801 (10) [back to overview]Time to Onset of Symptom Relief (TOSR)
NCT01919801 (10) [back to overview]Area Under the Plasma Concentration Versus Time Curve (AUC) of Icatibant and Its Metabolites (M1 and M2)
NCT01919801 (10) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)
NCT01919801 (10) [back to overview]Percentage of Participants With Time to Meeting Discharge Criteria (TMDC) at Specified Time Points
NCT01919801 (10) [back to overview]Number of Participants Admitted to Hospital or Intensive Care Unit (ICU)
NCT01919801 (10) [back to overview]Number of Participants With Treatment Emergent Injection Site Reaction
NCT02045264 (12) [back to overview]Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites
NCT02045264 (12) [back to overview]Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites
NCT02045264 (12) [back to overview]Change From Baseline in Diastolic Blood Pressure
NCT02045264 (12) [back to overview]Change From Baseline in Pulse Rate
NCT02045264 (12) [back to overview]Change From Baseline in Systolic Blood Pressure
NCT02045264 (12) [back to overview]Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites
NCT02045264 (12) [back to overview]Peak Plasma Concentration (Cmax) of Icatibant and Metabolites
NCT02045264 (12) [back to overview]Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results
NCT02045264 (12) [back to overview]The Percentage of Subjects With Any Injection Site Reactions.
NCT02045264 (12) [back to overview]Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites
NCT02045264 (12) [back to overview]The Total Number of Treatment-Emergent Adverse Events
NCT02045264 (12) [back to overview]Total Body Clearance (CL/F) of Icatibant
NCT03177798 (2) [back to overview]Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)
NCT03177798 (2) [back to overview]Systolic Blood Pressure
NCT03888755 (18) [back to overview]Change From Baseline in the Composite Visual Analog Scale (VAS) Score
NCT03888755 (18) [back to overview]Number of Participants With Injection Site Reactions Reported as Adverse Event (AE)
NCT03888755 (18) [back to overview]Area Under the Concentration-time Curve From 0 to 2 Hours (AUC0-2) After a Single Subcutaneous (SC) Administration of Icatibant
NCT03888755 (18) [back to overview]Area Under the Concentration-time Curve From 0 to 4 Hours (AUC0-4) After a Single Subcutaneous (SC) Administration of Icatibant
NCT03888755 (18) [back to overview]Area Under the Concentration-time Curve From 0 to 6 Hours (AUC0-6) After a Single Subcutaneous (SC) Administration of Icatibant
NCT03888755 (18) [back to overview]Composite Symptom Score (SS) Assessed by Investigator
NCT03888755 (18) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Icatibant After a Single Subcutaneous (SC) Administration of Icatibant
NCT03888755 (18) [back to overview]Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Adverse Event (AE)
NCT03888755 (18) [back to overview]Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Adverse Event (AE)
NCT03888755 (18) [back to overview]Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Event (AE)
NCT03888755 (18) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
NCT03888755 (18) [back to overview]Time to Almost Complete Symptom Relief As Assessed by Visual Analog Scale (VAS) Score
NCT03888755 (18) [back to overview]Time to Initial Symptom Improvement by Investigator
NCT03888755 (18) [back to overview]Time to Initial Symptom Improvement by Participants
NCT03888755 (18) [back to overview]Time to Onset of Primary Symptom Relief (TOSR-P)
NCT03888755 (18) [back to overview]Time to Onset of Symptom Relief (TOSR)
NCT03888755 (18) [back to overview]Composite Symptom Score (SS) Assessed by Participant
NCT03888755 (18) [back to overview]Investigator Global Assessment
NCT04654351 (16) [back to overview]Plasma Concentration for TAK-667
NCT04654351 (16) [back to overview]Number of Participants Who Experience at Least One TEAE Related to Clinically Significant Changes in Reproductive Hormones
NCT04654351 (16) [back to overview]Time to Initial Symptom Improvement Reported by Participant
NCT04654351 (16) [back to overview]Time to Initial Symptom Improvement Reported by Investigator
NCT04654351 (16) [back to overview]Number of Participants With Worsened Intensity of Clinical HAE Symptoms Between 2 and 4 Hours After Treatment With SC Icatibant Using Investigator-Rated Symptom Scores
NCT04654351 (16) [back to overview]Number of Participants With Injection Site Reactions
NCT04654351 (16) [back to overview]Number of Participants Who Were Treated With Rescue Medication During Study
NCT04654351 (16) [back to overview]Number of Participants Who Reported Presence of Anti-icatibant Antibodies
NCT04654351 (16) [back to overview]Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Events (TEAE)
NCT04654351 (16) [back to overview]Number of Participants Who Experienced at Least One TEAE Related to Vital Sign
NCT04654351 (16) [back to overview]Number of Participants Who Experienced at Least One TEAE Related to Resting 12-lead Electrocardiogram
NCT04654351 (16) [back to overview]Number of Participants Who Experienced at Least One TEAE Related to Clinical Laboratory Parameters
NCT04654351 (16) [back to overview]Time to Onset of Symptom Relief With Faces Pain Scale-Revised (FPS-R) Scores for Participants of 4 Years Age and Older
NCT04654351 (16) [back to overview]Time to Onset of Symptom Relief With Investigator-Rated Symptom Scores Assessed by Investigator
NCT04654351 (16) [back to overview]Plasma Concentration for TAK-667 Metabolite M-I
NCT04654351 (16) [back to overview]Plasma Concentration for TAK-667 Metabolite M-II

Time to Regression (Start of Improvement) According to Patient

"This parameter assessed the time to regression (start of improvement) of observable(visible) symptoms according to the patients. Patients were asked Report date and time when you feel that your symptoms start to improve." (NCT00097695)
Timeframe: 5 days

InterventionHours (Median)
Randomized -Icatibant0.8
Randomized -Placebo16.9

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Time to Onset of Symptom Relief (TOSR)

The primary efficacy endpoint was TOSR assessed by the patient using a Visual Analogue Scale (VAS). The VAS is a scale used to measure intensity of each symptom of the attack at baseline and at the pre-determined time points throughout treatment period. It consists of a horizontal 10cm line, with the 0 point corresponding to a state where patient experiences no symptoms at all and the 10cm point represents the worst symptoms ever experienced by patient. The patient indicates his/her current state of symptoms by drawing a mark across the horizontal line. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the 3 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. (NCT00097695)
Timeframe: 5 days

InterventionHours (Median)
Randomized -Icatibant2.5
Randomized -Placebo4.6

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Time to Almost Complete Symptom Relief

The time to almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least 3 consecutive measurements for all symptom. (NCT00097695)
Timeframe: 5 days

InterventionHours (Median)
Randomized Control Trial-icatibant8.5
Randomized Control Trial-placebo19.4

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Inflammatory Response as Measured by Interleukin-6

Interleukin-6 was measured at baseline, post-bypass and on postoperative day 1 and 2. (NCT00223704)
Timeframe: Patients were followed from the start of surgery until postoperative day 2

,,
Interventionpg/ml (Mean)
BaselinePost-bypassPostoperative day 1Postoperative day 2
Aminocaproic Acid Group6.5864.65161.91122.88
HOE 140 Group4.80142.02166.2786.54
Placebo Group4.9868.8118.8201.5

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Fibrinolytic Response as Measured by D-dimer

D-dimer concentrations were measured at baseline, 30min and 60min of bypass, post-bypass and postoperative day 1 (NCT00223704)
Timeframe: Patients were followed from the start of surgery until postoperative day 1

,,
Interventionng/ml (Mean)
Baseline30min of bypass60min of bypassPost-bypassPostoperative day 1
Aminocaproic Acid Group103.0131.9154.3168.9269.5
HOE 140 Group88.1209.0363.3858.5337.3
Placebo Group95.5150.6287.6589.8390.4

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Allogenic Blood Product Transfusion Risk

Blood product transfusion during hospitalization that included packed red blood cells, plasma, platelets and cryoprecipitate. (NCT00223704)
Timeframe: Patients were followed for the duration of hospital stay, an average of 6 days

,,
Interventionpercentage of participants (Number)
Received any transfusionReceived packed red blood cellsReceived plasmaReceived plateletsReceived cryoprecipitate
Aminocaproic Acid Group56.848.624.316.22.7
HOE 140 Group52.547.517.517.55.0
Placebo Group47.436.831.623.710.5

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Units of Plasma Transfused During Hospitalization

Units of plasma transfused (NCT00223704)
Timeframe: Patients were followed for the duration of hospital stay, an average of 6 days

Interventionunits (Mean)
Placebo Group1.08
Aminocaproic Acid Group0.68
HOE 140 Group0.82

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Units of Packed Red Blood Cells Transfused During Hospitalization

Units of Packed Red Blood Cells Transfused (NCT00223704)
Timeframe: Patients were followed for the duration of hospital stay, an average of 6 days

Interventionunits (Mean)
Placebo Group1.97
Aminocaproic Acid Group1.41
HOE 140 Group1.45

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Time to Almost Complete Symptom Relief

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. (NCT00500656)
Timeframe: 48 hours

InterventionHours (Median)
Randomized Controlled -Icatibant10.0
Randomized Controlled-Tranexamic Acid51.0

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Time to Onset of Symptom Relief.

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. (NCT00500656)
Timeframe: 2 days

InterventionHours (Median)
Randomized Controlled -Icatibant2.0
Randomized Controlled-Tranexamic Acid12.0

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Time to Almost Complete Symptom Relief

Time to almost complete symptom relief was calculated from the time of study drug administration to almost complete symptom relief, where almost complete symptom relief was defined as the earliest of 3 consecutive non-missing measurements in which all VAS scores <10 mm. Subjects who did not achieve almost complete symptom relief within the observation period were censored at the last observation time. (NCT00912093)
Timeframe: Up to 120 Hours post treatment

InterventionHours (Median)
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal8.0
Randomized-Placebo (Blinded Treatment)-Non-laryngeal36.0

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Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient

Time to onset of symptom relief was calculated from study drug administration to onset of symptom relief, where onset of symptom relief was defined as the earliest of 3 consecutive measurements in which there was a 50% reduction from pretreatment in composite VAS score. Composite VAS score comprised 3 symptoms, including skin swelling, skin pain, and abdominal pain, for cutaneous and abdominal attacks and 5 symptoms, including skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change, for laryngeal attacks. Subjects who did not achieve symptom relief within the observation period were censored at the last observation time. (NCT00912093)
Timeframe: Up to 120 hours post-dose

InterventionHours (Median)
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal2.0
Randomized-Placebo (Blinded Treatment)-Non-laryngeal19.8

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Time to Subject-Assessed Initial Symptom Improvement

Time to initial symptom improvement was calculated from the time of study drug administration to initial symptom improvement as determined by the subject as the time they felt symptoms were starting to improve. Subjects who did not achieve initial symptom improvement within the observation period were censored at the last observation time. (NCT00912093)
Timeframe: Up to 120 hours post-dose

InterventionHours (Median)
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal0.8
Randomized-Placebo (Blinded Treatment)-Non-laryngeal3.5

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Time to Onset of Primary Symptom Relief

Time to primary symptom relief was calculated from the time of study drug administration to the onset of primary symptom relief, where onset of primary symptom relief was determined using the subject-assessed VAS score for a single primary symptom (determined by edema location) and defined as the earliest of 3 consecutive non-missing measurements in which a pre-specified reduction from the pretreatment value was met. Subjects who did not achieve primary symptom relief within the observation period were censored at the last observation time. (NCT00912093)
Timeframe: Up to 120 hours post-dose

InterventionHours (Median)
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal1.5
Randomized-Placebo (Blinded Treatment)-Non-laryngeal18.5

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Time to Investigator-Assessed Initial Symptom Improvement

Time to initial symptom improvement was calculated from the time of study drug administration to initial symptom improvement as determined by the investigator as the time they felt symptoms were starting to improve. Subjects who did not achieve initial symptom improvement within the observation period were censored at the last observation time. (NCT00912093)
Timeframe: Up to 120 hours post-dose

InterventionHours (Median)
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal0.8
Randomized-Placebo (Blinded Treatment)-Non-laryngeal3.4

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Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant

Clinical safety of self-treatment of acute HAE attacks with s.c. injections of icatibant was assessed by calculating the number of AEs occurred during the study. Only those adverse events occurring up to the earlier of 7 days from the start of the naive phase, study discontinuation and start of the self-administration phase are assessed. The Local Tolerability Assessment tool was used. Subjects and Investigators graded erythema/reddening, swelling, burning, pruritus/itching, warm sensation, and skin pain on a 0 to 3 severity scale. (NCT00997204)
Timeframe: 7 days from the beginning of each phase

Interventionparticipants (Number)
Naive Subjects Administered Icatibant by Health Care Provider11
Subjects Who Self-administered Icatibant (Naive)6
Subjects Who Self-administered Icatibant (Non-naive)27

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Clinical Efficacy of Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant, Time to Symptom Relief Using VAS Score for a Single Primary Symptom by Patient Cohort

"Subjects assessed angioedema attack symptoms using the visual analogue scale (VAS) for skin pain, skin swelling and abdominal pain. The VAS is a continuous scale comprised of a 100 mm in length line, anchored by 2 verbal descriptors, one for each symptom extreme 0 (no pain) and 100 (worst pain). The respondent is asked to place a mark on the VAS line (any where between 0 and 100 mm) at the point that represents their pain intensity. The score is determined by measuring the distance (mm) on the line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. Score interpretation is: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). Symptom relief is defined as at least a 50% reduction in a pre-dose VAS score of 30 mm or greater. The time to onset of symptom relief is defined as the first of 3 consecutive assessments at which symptom relief was observed." (NCT00997204)
Timeframe: 48 hours post-dose

InterventionHours (Median)
Naive Subjects Administered Icatibant by Health Care Provider2.0
Subjects Who Self-administered Icatibant (Naive)3.1
Subjects Who Self-administered Icatibant (Non-naive)2.0

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Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3

Time to minimum symptom was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which all symptoms were either mild or absent for the investigator-reported symptom score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). Time to minimum symptom for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported. (NCT01386658)
Timeframe: From start of study drug administration up to 12 hours post-dose

Interventionh (Median)
Icatibant Exposure-2: Caregiver AdministrationIcatibant Exposure-3: Caregiver Administration
Pubertal/Postpubertal1.22.2

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Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant

Area under the plasma concentration-time curve from time zero to 6 hours post-dose (AUC0-t) of a single SC dose of icatibant was reported. (NCT01386658)
Timeframe: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1

Interventionh*ng/mL (Mean)
Prepubertal1289
Pubertal/Postpubertal: With Acute Attack1573
Pubertal/Postpubertal: Without Acute Attack1398

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Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant

Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of a single SC dose of icatibant was reported. (NCT01386658)
Timeframe: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1

Interventionh*ng/mL (Mean)
Prepubertal1243
Pubertal/Postpubertal: With Acute Attack1710
Pubertal/Postpubertal: Without Acute Attack1416

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Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant

Elimination half-life (t1/2) of a single SC dose of icatibant was reported. (NCT01386658)
Timeframe: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1

Interventionh (Mean)
Prepubertal0.80
Pubertal/Postpubertal: With Acute Attack1.34
Pubertal/Postpubertal: Without Acute Attack0.90

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Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant

Maximum plasma concentration (Cmax) of a single SC dose of icatibant was reported. (NCT01386658)
Timeframe: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1

InterventionNanogram per milliliter (ng/mL) (Mean)
Prepubertal659
Pubertal/Postpubertal: With Acute Attack805
Pubertal/Postpubertal: Without Acute Attack761

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Number of Participants Who Reported Presence of Anti-icatibant Antibodies

The number of participants who reported anti-icatibant antibodies were reported. (NCT01386658)
Timeframe: Pre-dose up to 97 days post-dose

InterventionParticipants (Count of Participants)
Prepubertal0
Pubertal/Postpubertal0

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Number of Participants With Adverse Events (AEs)

An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in a clinical study, whether or not considered investigational product related. (NCT01386658)
Timeframe: From the start of study drug administration up to 97 days post-dose

InterventionParticipants (Count of Participants)
Prepubertal2
Pubertal/Postpubertal11

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Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations

Clinical laboratory evaluations included clinical chemistry (including liver function tests), hematology, urinalysis. The number of participants who reported clinically significant changes in clinical laboratory evaluations were reported. (NCT01386658)
Timeframe: Pre-dose up to 97 days post-dose

InterventionParticipants (Count of Participants)
Prepubertal0
Pubertal/Postpubertal0

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Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs)

A standard 12-lead ECG was performed after 10 minutes at rest when the participant was seated or supine following treatment. The number of participants who reported clinically significant changes in ECGs were reported. (NCT01386658)
Timeframe: 6 - 8 hours post-dose on Day 1

InterventionParticipants (Count of Participants)
Prepubertal0
Pubertal/Postpubertal0

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Number of Participants With Clinically Significant Changes in Reproductive Hormones

Reproductive hormone levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone in females, and FSH, LH, and testosterone in males were measured. The number of participants with clinically significant changes in reproductive hormones was reported. (NCT01386658)
Timeframe: Pre-dose up to 97 days post-dose

InterventionParticipants (Count of Participants)
Prepubertal0
Pubertal/Postpubertal0

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Number of Participants With Clinically Significant Changes in Vital Signs

Vital signs included pulse rate, blood pressure, respiration rate, and temperature. The number of participants who reported clinically significant changes in vital signs were reported. (NCT01386658)
Timeframe: Pre-dose up to 97 days post-dose

InterventionParticipants (Count of Participants)
Prepubertal0
Pubertal/Postpubertal0

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Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1

Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which post-treatment score improved to zero (or no pain). Participants of 4 years of age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). Time to minimum symptom for participants who received initial icatibant administration was reported. (NCT01386658)
Timeframe: From start of study drug administration up to 52 hours post-dose

Interventionh (Median)
Prepubertal2.4
Pubertal/Postpubertal3.8

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Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1

Time to minimum symptom was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which all symptoms were either mild or absent for the investigator-reported symptom score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). Time to minimum symptom for participants who received initial icatibant administration was reported. (NCT01386658)
Timeframe: From start of study drug administration up to 8.5 hours post-dose

Interventionh (Median)
Prepubertal1.9
Pubertal/Postpubertal1.0

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Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1

The TOSR was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which there was at least a 20 percent (%) improvement in the average post-treatment symptom score with no worsening of any single component score for the initial icatibant exposure. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of hereditary angioedema (HAE) using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). TOSR for participants who received initial icatibant administration was reported. (NCT01386658)
Timeframe: From start of study drug administration up to 8.5 hours post-dose

Interventionh (Median)
Prepubertal1.0
Pubertal/Postpubertal1.0

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Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1

The TOSR was defined as the earliest time at which the post-treatment score improved by at least one level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). TOSR for participants who received initial icatibant administration was reported. (NCT01386658)
Timeframe: From start of study drug administration up to 52 hours post-dose

Interventionh (Median)
Prepubertal0.9
Pubertal/Postpubertal1.0

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Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant

Area under the plasma concentration-time curve from time zero to 4 hours post-dose (AUC0-4) of a single SC dose of icatibant was reported. (NCT01386658)
Timeframe: Pre-dose; 0.25, 0.5, 0.75, 1, 2, and 4 hours post-dose on Day 1

InterventionHour*nanogram per milliliter (h*ng/mL) (Mean)
Prepubertal1241
Pubertal/Postpubertal: With Acute Attack1448
Pubertal/Postpubertal: Without Acute Attack1335

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Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant

Time to peak concentration (Tmax) of a single SC dose of icatibant was reported. (NCT01386658)
Timeframe: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1

InterventionHour (h) (Mean)
Prepubertal0.42
Pubertal/Postpubertal: With Acute Attack0.55
Pubertal/Postpubertal: Without Acute Attack0.57

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Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration

"Rescue medication was any medication used after the administration of icatibant which, in the opinion of the investigator, was immediately necessary to alleviate acute symptoms which are judged by the investigator as resultant from the current HAE attack. Time to first use of rescue medication prior to the onset of symptom relief was calculated from the time of study drug administration to the first use of rescue medication prior to the onset of symptom relief. This analysis was not performed since as per protocol, This analysis will only be performed if there are at least 5 participants for a given attack who used rescue medication prior to attaining symptom relief." (NCT01386658)
Timeframe: From the start of study drug administration up to 52 hours post-dose

Interventionh (Median)
PrepubertalNA
Pubertal/PostpubertalNA

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Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant

Total plasma clearance (CL/F) of a single SC dose of icatibant was reported. (NCT01386658)
Timeframe: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1

InterventionMilliliters per minute (mL/min) (Mean)
Prepubertal10.8
Pubertal/Postpubertal: With Acute Attack13.1
Pubertal/Postpubertal: Without Acute Attack19.3

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Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant

Volume of distribution (Vz/F) of a single SC dose of icatibant was reported. (NCT01386658)
Timeframe: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1

InterventionLiters (L) (Mean)
Prepubertal12.5
Pubertal/Postpubertal: With Acute Attack23.5
Pubertal/Postpubertal: Without Acute Attack25.4

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Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1

The number of participants with injection site reactions (erythema, swelling, burning sensation, itching/pruritus, warm sensation, cutaneous pain, or other) that occured after initial icatibant administration was reported. (NCT01386658)
Timeframe: 1 h post-dose on Day 1 up to 9 days post-dose

,
InterventionParticipants (Count of Participants)
Any ReactionAny Severe Reaction
Prepubertal90
Pubertal/Postpubertal202

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Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3

The number of participants with injection site reactions (erythema, swelling, burning sensation, itching/pruritus, warm sensation, cutaneous pain, or other) that occurred after subsequent icatibant administration by study-site personnel (health care practitioner [HCP] administration) or by caregiver/self (caregiver administration) was reported. In the below table, E-2 refers to icatibant exposure 2 and E-3 refers to icatibant exposure 3. (NCT01386658)
Timeframe: 1 h post-dose up to 9 days post-dose

InterventionParticipants (Count of Participants)
E-2: HCP Administration: Any ReactionE-2: HCP Administration: Any Severe ReactionE-2: Caregiver Administration: Any ReactionE-2: Caregiver Administration: Any Severe ReactionE-3: HCP Administration: Any ReactionE-3: HCP Administration: Any Severe ReactionE-3: Caregiver Administration: Any ReactionE-3: Caregiver Administration: Any Severe Reaction
Pubertal/Postpubertal10831071

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Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1

The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5- point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). The number of participants with a worsened severity of HAE symptoms at 4 hours post-dose from 2 hours postdose were reported. (NCT01386658)
Timeframe: From 2 hours post-dose to 4 hours post-dose

,
InterventionParticipants (Count of Participants)
Abdominal TendernessNauseaVomitingDiarrheaSkin PainErythemaSkin IrritationSkin Swelling
Prepubertal00000000
Pubertal/Postpubertal10000000

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Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3

The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5- point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). The number of participants with a worsened severity of HAE symptoms at 4 hours post-dose from 2 hours post-dose were reported. (NCT01386658)
Timeframe: From 2 hours post-dose to 4 hours post-dose

InterventionParticipants (Count of Participants)
E-2: HCPA: Abdominal TendernessE-2:CA: Abdominal TendernessE-2: HCPA: NauseaE-2: CA: NauseaE-2:HCPA: VomitingE-2: CA: VomitingE-2: HCPA: DiarrheaE-2: CA: DiarrheaE-2: HCPA: Skin PainE-2: CA: Skin PainE-2: HCPA: ErythemaE-2: CA: ErythemaE-2: HCPA: Skin IrritationE-2: CA: Skin IrritationE-2: HCPA: Skin SwellingE-2: CA: Skin SwellingE-2: HCPA: DysphagiaE-2: CA: DysphagiaE-2: HCPA: Voice ChangeE-2: CA: Voice ChangeE-2: HCPA: Breathing DifficultiesE-2: CA: Breathing DifficultiesE-2: HCPA: StridorE-2: CA: StridorE-2: HCPA: AsphyxiaE-2:CA: AsphyxiaE-3: HCPA: Abdominal TendernessE-3: CA: Abdominal TendernessE-3: HCPA: NauseaE-3: CA: NauseaE-3: HCPA: VomitingE-3: CA: VomitingE-3: HCPA: DiarrheaE-3: CA: DiarrheaE-3: HCPA: Skin PainE-3: CA: Skin PainE-3: HCPA: ErythemaE-3: CA: ErythemaE-3: HCPA: Skin IrritationE-3: CA: Skin IrritationE-3: HCPA: Skin SwellingE-3: CA: Skin SwellingE-3: HCPA: DysphagiaE-3: CA: DysphagiaE-3: HCPA: Voice ChangeE-3: CA: Voice ChangeE-3: HCPA: Breathing DifficultiesE-3: CA: Breathing DifficultiesE-3: HCPA: StridorE-3: CA: StridorE-3: HCPA: AsphyxiaE-3: CA: Asphyxia
Pubertal/Postpubertal0000000000000000000000000001000001000000000000000000

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Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3

Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which post-treatment score improved to zero (or no pain). Participants of 4 years of age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). Time to minimum symptom for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported. (NCT01386658)
Timeframe: From start of study drug administration up to 28 hours post-dose

Interventionh (Median)
Icatibant Exposure-2: HCP AdministrationIcatibant Exposure-2: Caregiver AdministrationIcatibant Exposure-3: HCP AdministrationIcatibant Exposure-3:Caregiver Administration
Pubertal/Postpubertal3.02.15.824.0

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Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3

The TOSR was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which there was at least a 20% improvement in the composite (or average) post-treatment symptom score with no worsening of any single component score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). TOSR for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported. (NCT01386658)
Timeframe: From start of study drug administration up to 12 hours post-dose

Interventionh (Median)
Icatibant Exposure-2: HCP AdministrationIcatibant Exposure-2: Caregiver AdministrationIcatibant Exposure-3: HCP AdministrationIcatibant Exposure-3:Caregiver Administration
Pubertal/Postpubertal4.01.01.01.1

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Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3

The TOSR was defined as the earliest time at which the post-treatment score improved by at least one level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). TOSR for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported. (NCT01386658)
Timeframe: From start of study drug administration up to 28 hours post-dose

Interventionh (Median)
Icatibant Exposure-2: HCP AdministrationIcatibant Exposure-2: Caregiver AdministrationIcatibant Exposure-3: HCP AdministrationIcatibant Exposure-3:Caregiver Administration
Pubertal/Postpubertal3.01.01.01.1

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Time to Onset of Symptom Relief (TOSR) for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores

The TOSR was defined as the earliest time at which a 20% improvement was seen in the total post-treatment score. Participants of 4 years age and younger underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC comportmental pain scale. Each of the 5 categories was scored from 0 to 2. Face(F): 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); Legs(L): 0 (normal position/relaxed) - 2 (kicking/legs drawn up); Activity(A): 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); Cry(C): 0 (No cry [awake/asleep]) - 2 (crying steadily/screams/sobs or frequent complaints); Consolability(C): 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10. (NCT01386658)
Timeframe: From start of study drug administration up to 8.5 hours post-dose

Interventionh (Median)
Prepubertal1.0

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Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores

Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which the total post-treatment score improved to zero. Participants of 4 years age and younger underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC comportmental pain scale. Each of the 5 categories was scored from 0 to 2. (F) Face: 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); (L) Legs: 0 (normal position/relaxed) - 2 (kicking/legs drawn up); (A) Activity: 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); (C) Cry: 0 (No cry [awake/asleep]) - 2 (crying steadily/screams/sobs or frequent complaints); (C) Consolability: 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10. (NCT01386658)
Timeframe: From start of study drug administration up to 8.5 hours post-dose

Interventionh (Median)
Prepubertal1.0

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Time to Complete or Near Complete Resolution From Onset of Symptoms

Time of onset of HAE attack, time icatibant was administered, and time to complete relief of symptoms were recorded in minutes. Time to complete relief of symptoms was defined as time from onset of symptoms to complete or near complete resolution as reported by the patient. (NCT01457430)
Timeframe: Time to complete or near complete resolution of symptoms as reported by the patient, an expected average of 8-10 hours

Interventionminutes (Median)
Icatibant Treatment With Health Care Provider735
Icatibant Treatment by Self Administration377

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Percent Change in VAS Scores

Baseline, 4 hours VAS scale ranges from 0-100 with 0 being the lowest severity and 100 being the highest severity (NCT01457430)
Timeframe: Percent Change in VAS Score from Baseline to 4 Hours

Interventionpercent change (Median)
Icatibant Treatment With Health Care Provider-97
Icatibant Treatment by Self Administration-96

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Number of Participants Given Steroids

(NCT01574248)
Timeframe: T0 to T48 hours

InterventionParticipants (Count of Participants)
Icatibant11
Placebo16

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Number of Participants With Admission to Intensive Care Unit

(NCT01574248)
Timeframe: T0 to T48 hours

InterventionParticipants (Count of Participants)
Icatibant6
Placebo6

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Number of Participants With Requirement for Intubation

(NCT01574248)
Timeframe: T0 to T48 hours

InterventionParticipants (Count of Participants)
Icatibant2
Placebo1

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Systolic Blood Pressure

Average of blood pressure measurements from zero to forty-eight hours provided. (NCT01574248)
Timeframe: T0 to T48 hours

InterventionmmHg (Mean)
Icatibant134
Placebo133

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Time to Resolution of Angioedema

Time interval between initiation of treatment and when there is no symptom, by visual analog scale <1 cm. Data provided are for worst symptom. (NCT01574248)
Timeframe: 48 hours

Interventionhours (Median)
Icatibant36
Placebo24

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Number of Participants Given Epinephrine

(NCT01574248)
Timeframe: T0 to T48 hours

InterventionParticipants (Count of Participants)
Icatibant0
Placebo3

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Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers

(NCT01574248)
Timeframe: T0 to T48 hours

InterventionParticipants (Count of Participants)
Icatibant11
Placebo16

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Number of Participants Experienced ACE-I-induced Angioedema Attack Following Study Drug Administration

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. (NCT01919801)
Timeframe: Day 0 up to Day 5

Interventionparticipants (Number)
Icatibant 30 mg35
Placebo35

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Number of Participants Experienced Airway Intervention Due to ACE-I-induced Angioedema

Airway Intervention included intubation, tracheotomy, cricothyrotomy. (NCT01919801)
Timeframe: Day 0 up to Day 5

Interventionparticipants (Number)
Icatibant 30 mg1
Placebo0

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Number of Participants With Clinically Significant Changes in Laboratory Evaluation, Vital Signs, Electrocardiogram (ECG) and Physical Examination

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. (NCT01919801)
Timeframe: Day 0 to Day 5

Interventionparticipants (Number)
Icatibant 30 mg0
Placebo0

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Time to Meeting Discharge Criteria (TMDC)

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. (NCT01919801)
Timeframe: Day 0 up to Day 5

Interventiondays (Median)
Icatibant 30 mg4.03
Placebo4.00

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Time to Onset of Symptom Relief (TOSR)

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. (NCT01919801)
Timeframe: Day 0 up to Day 5

Interventiondays (Median)
Icatibant 30 mg2.00
Placebo1.55

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Area Under the Plasma Concentration Versus Time Curve (AUC) of Icatibant and Its Metabolites (M1 and M2)

Area under the plasma concentration-time curve of Icatibant and its metabolites (M1 and M2) were analyzed. A population pharmacokinetic analysis approach using sparse pharmacokinetic sampling obtained from a subset of subjects was used to evaluate exposure to icatibant. (NCT01919801)
Timeframe: 0.75 and 2 hours post-dose

Interventionhours*nanogram per milliliter (h*ng/mL) (Mean)
IcatibantMetabolite M1Metabolite M2
Icatibant 30 mg253028903180

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Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)

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. (NCT01919801)
Timeframe: From start of study drug administration (Day 0) up to follow-up (Day 5)

,
Interventionparticipants (Number)
Participants with TEAEsParticipants with TESAEs
Icatibant 30 mg272
Placebo211

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Percentage of Participants With Time to Meeting Discharge Criteria (TMDC) at Specified Time Points

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. (NCT01919801)
Timeframe: 4, 6, and 8 hours post treatment

,
Interventionpercentage of participants (Number)
At 4 hours post treatmentAt 6 hours post treatmentAt 8 hours post treatment
Icatibant 30 mg55.078.391.7
Placebo60.375.991.4

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Number of Participants Admitted to Hospital or Intensive Care Unit (ICU)

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. (NCT01919801)
Timeframe: Day 0 up to Day 5

Interventionparticipants (Number)
Icatibant 30 mg22
Placebo22

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Number of Participants With Treatment Emergent Injection Site Reaction

Injection site reaction included erythema, swelling, cutaneous pain, burning sensation, itching and warm sensation (NCT01919801)
Timeframe: Day 0 to Day 5

,
Interventionparticipants (Number)
ErythemaSwellingCutaneous painBurning sensationItchingWarm sensation
Icatibant 30 mg311710151316
Placebo13137768

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Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites

AUCinf is the area under the plasma concentration versus time curve extrapolated from time 0 to infinity, calculated using the observed value of the last non-zero concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. (NCT02045264)
Timeframe: Over 48 hours post-dose

Interventionng*hr/mL (Mean)
IcatibantMetabolite 1Metabolite 2
Icatibant (30 mg)232017501960

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Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites

AUC0-t is the area under the plasma concentration versus time curve extrapolated from time 0 to to the last quantifiable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. (NCT02045264)
Timeframe: Over 48 hours post-dose

Interventionng*hr/mL (Mean)
IcatibantMetabolite 1Metabolite 2
Icatibant (30 mg)232017401950

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Change From Baseline in Diastolic Blood Pressure

(NCT02045264)
Timeframe: Over 48 hours post-dose

InterventionmmHg (Mean)
Day 1, 0.5 hDay 1, 1 hDay 1, 2 hDay 1, 4 hDay 1, 6 hDay 1, 8 hDay 1, 12 hDay 2, 24 hDay 3, 48 h
Icatibant (30 mg)-2.0-3.8-5.2-5.2-4.8-4.5-3.4-1.8-5.3

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Change From Baseline in Pulse Rate

(NCT02045264)
Timeframe: Over 48 hours post-dose

Interventionbeats per minute (Mean)
Day 1, 0.5 hDay 1, 1 hDay 1, 2 hDay 1, 4 hDay 1, 6 hDay 1, 8 hDay 1, 12 hDay 2, 24 hDay 3, 48 h
Icatibant (30 mg)1.40.1-3.0-6.3-0.1-3.6-3.2-6.8-4.0

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Change From Baseline in Systolic Blood Pressure

(NCT02045264)
Timeframe: Over 48 hours post-dose

InterventionmmHg (Mean)
Day 1, 0.5 hDay 1, 1 hDay 1, 2 hDay 1, 4 hDay 1, 6 hDay 1, 8 hDay 1, 12 hDay 2, 24 hDay 3, 48 h
Icatibant (30 mg)-1.8-1.9-5.8-7.3-4.3-3.0-4.4-6.2-6.4

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Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites

The time it takes for the blood plasma concentration of a substance to halve. (NCT02045264)
Timeframe: Over 48 hours post-dose

Interventionhr (Mean)
IcatibantMetabolite 1Metabolite 2
Icatibant (30 mg)1.773.694.11

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Peak Plasma Concentration (Cmax) of Icatibant and Metabolites

Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated. (NCT02045264)
Timeframe: Over 48 hours post-dose

Interventionng/mL (Mean)
IcatibantMetabolite 1Metabolite 2
Icatibant (30 mg)1190340365

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Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results

(NCT02045264)
Timeframe: Over 48 hours post-dose

Interventionpercentage of participants (Number)
ScreeningDay 1, Pre-doseBaselineDay 1, 0.75 hoursDay 1, 8 hoursDay 2, 24 hoursDay 3, 48 hours
Icatibant (30 mg)91.6750.0050.0033.3333.3366.6766.67

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The Percentage of Subjects With Any Injection Site Reactions.

(NCT02045264)
Timeframe: Over 48 hours post-dose

Interventionpercentage of participants (Number)
ErythemaWarm sensationSwellingCutaneous painItching/PruritusBurning sensation
Icatibant (30 mg)100.0050.0091.6733.338.338.33

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Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites

Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached. (NCT02045264)
Timeframe: Over 48 hours post-dose

Interventionhr (Mean)
IcatibantMetabolite 1Metabolite 2
Icatibant (30 mg)0.671.921.92

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The Total Number of Treatment-Emergent Adverse Events

Treatment-emergent adverse events (TEAEs) were those that started after the single dose of icatibant. (NCT02045264)
Timeframe: TEAEs were collected after the single dose of icatibant until follow up, 5-7 days after icatibant administration

InterventionTreatment Emergent Adverse Events (Number)
Icatibant (30 mg)2

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Total Body Clearance (CL/F) of Icatibant

The rate at which a drug is removed from the body. (NCT02045264)
Timeframe: Over 48 hours post-dose

InterventionmL/hr (Mean)
Icatibant (30 mg)13200

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Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)

Mitochondria function will be evaluated using 31P-MRS, which evaluates the concentration of phospho-creatine (PCr) and other phosphate-energy carrier molecules. After basal measurements, subjects will be asked to perform 90 seconds of knee extension followed by 4 minutes of rest. The exercise/rest cycle will be repeated 3 times. Magnetic resonance spectra will be used to calculate concentrations of inorganic phosphate (Pi), PCr, and adenosine triphosphate (ATP). The time constant tau of PCr recovery (time to achieve 66.3% maximal concentration during recovery) will be used to determine mitochondrial function. (NCT03177798)
Timeframe: Up to 2 hours after completion of drug infusion

Interventionseconds (Mean)
Icatibant60.59
Placebo62.66

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Systolic Blood Pressure

Blood pressure will be monitored every 15 minutes, before, during, and after hemodialysis. (NCT03177798)
Timeframe: 30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis

,
InterventionmmHg (Mean)
30 minutes before hemodialysisduring dialysisup to 1 hour after hemodialysis
Icatibant123.36122.5454545119.09
Placebo125.27122.18124.09

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Change From Baseline in the Composite Visual Analog Scale (VAS) Score

A VAS utilizes a scale consisting of a 100 mm horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The participant should draw a vertical line at the point along the scale that represents the current status of the measured symptom. Composite VAS scores was calculated as the average of VAS measurements for skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change (5-symptom composite) for laryngeal attacks and as the average of VAS measurements for skin swelling, skin pain and abdominal pain (3-symptom composite) for non-laryngeal attacks. Change from baseline in the composite VAS score was reported. (NCT03888755)
Timeframe: Baseline, 2, 4 and 8 hours post-treatment

InterventionScore on a scale (Mean)
Baseline2 hours4 hours8 hours
Icatibant30.78-19.26-24.57-29.40

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Number of Participants With Injection Site Reactions Reported as Adverse Event (AE)

Number of participants with injection site reactions (erythema, swelling, cutaneous pain, burning sensation, itching/pruritus, and warm sensation) were reported. (NCT03888755)
Timeframe: From start of study drug administration to follow-up (up to 10 days)

InterventionParticipants (Count of Participants)
Any ReactionAny Severe Reaction
Icatibant71

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Area Under the Concentration-time Curve From 0 to 2 Hours (AUC0-2) After a Single Subcutaneous (SC) Administration of Icatibant

The AUC0-2 was estimated by a population PK modeling approach. The AUC0-2 of Icatibant was reported. (NCT03888755)
Timeframe: Baseline, 0.75, 2 hours post-treatment

InterventionNanograms*hour per milliliter (ng•h/mL) (Mean)
Icatibant611

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Area Under the Concentration-time Curve From 0 to 4 Hours (AUC0-4) After a Single Subcutaneous (SC) Administration of Icatibant

The AUC0-4 was estimated by a population PK modeling approach. The AUC0-4 of Icatibant was reported. (NCT03888755)
Timeframe: Baseline, 0.75, 2 hours post-treatment

Interventionng•h/mL (Mean)
Icatibant1198

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Area Under the Concentration-time Curve From 0 to 6 Hours (AUC0-6) After a Single Subcutaneous (SC) Administration of Icatibant

The AUC0-6 was estimated by a population PK modeling approach. The AUC0-6 of Icatibant was reported. (NCT03888755)
Timeframe: Baseline, 0.75, 2 hours post-treatment

Interventionng•h/mL (Mean)
Icatibant1506

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Composite Symptom Score (SS) Assessed by Investigator

The investigator-assessed composite symptom score was calculated as an average of abdominal tenderness, nausea, vomiting, diarrhea, skin pain, erythema, skin irritation, and skin swelling (8 symptoms) for non-laryngeal attacks and the average of abdominal tenderness, nausea, vomiting, diarrhea, skin pain, erythema, skin irritation, skin swelling, dysphagia, voice change, breathing difficulties, stridor, and asphyxia (13 symptoms) for laryngeal attacks using the following 5-point scale 0 = none (absence of symptoms); 1 = mild (no to mild interference with daily activities); 2 = moderate (moderate interference with daily activities); 3 = severe (severe interference with daily activities); 4 = very severe (very severe interference with daily activities). Here the composite SS assessed by investigator was reported. (NCT03888755)
Timeframe: 8 hours post dose

InterventionScore on a scale (Mean)
Icatibant0.12

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Maximum Observed Plasma Concentration (Cmax) of Icatibant After a Single Subcutaneous (SC) Administration of Icatibant

The Cmax was estimated by a population PK modeling approach. The Cmax of icatibant was reported. (NCT03888755)
Timeframe: Baseline, 0.75, 2 hours post-treatment

InterventionNano grams per milliliter (ng/mL) (Mean)
Icatibant405

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Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Adverse Event (AE)

Clinical laboratory tests included serum chemistry, hematology, urinalysis and coagulation were assessed. Number of participants with clinically significant changes in clinical laboratory tests were reported. (NCT03888755)
Timeframe: From start of study drug administration to follow-up (up to 10 days)

InterventionParticipants (Count of Participants)
Icatibant0

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Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Adverse Event (AE)

A standard 12-lead ECG was performed. The number of participants who reported clinically significant changes in ECGs were reported. (NCT03888755)
Timeframe: From start of study drug administration to follow-up (up to 10 days)

InterventionParticipants (Count of Participants)
Icatibant0

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Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Event (AE)

Vital signs included pulse rate, blood pressure, respiration rate, and temperature. The number of participants with clinically significant changes in vital signs were reported. (NCT03888755)
Timeframe: From start of study drug administration to follow-up (up to 10 days)

InterventionParticipants (Count of Participants)
Icatibant0

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Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurred in any phase of a clinical study, whether or not considered investigational product related. The TEAEs were defined as all AEs occurred on or after the time of study drug administration. (NCT03888755)
Timeframe: From start of study drug administration to follow-up (up to 10 days)

InterventionParticipants (Count of Participants)
Icatibant3

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Time to Almost Complete Symptom Relief As Assessed by Visual Analog Scale (VAS) Score

Time to almost complete symptom relief was calculated from the time of icatibant administration to almost complete symptom relief. Almost complete symptom relief was determined retrospectively as the earliest of three consecutive non-missing measurements for which all VAS scores < 10 mm. A VAS utilizes a scale consisting of a 100 millimeter (mm) horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The participant should draw a vertical line at the point along the scale that represents the current status of the measured symptom. (NCT03888755)
Timeframe: Baseline up to 120 hours post-treatment

InterventionH (Median)
Icatibant5.98

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Time to Initial Symptom Improvement by Investigator

Time to initial symptom improvement was evaluated by the investigator; each were asked to record the time at which they perceived initial improvement of symptoms. Time to initial symptom improvement was calculated from the time of icatibant administration to the time reported by the investigator of initial improvement of symptoms. (NCT03888755)
Timeframe: Baseline up to 120 hours post-treatment

InterventionH (Median)
Icatibant0.98

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Time to Initial Symptom Improvement by Participants

Time to initial symptom improvement was evaluated by the participants; each were asked to record the time at which they perceived initial improvement of symptoms. Time to initial symptom improvement was calculated from the time of icatibant administration to the time reported by the participant of initial improvement of symptoms. (NCT03888755)
Timeframe: Baseline up to 120 hours post-treatment

Interventionh (Median)
Icatibant1.04

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Time to Onset of Primary Symptom Relief (TOSR-P)

Primary symptom relief was based on the participant-assessed VAS score for a single primary symptom (determined by edema location) and corresponds to a reduction by 31 mm at a pretreatment VAS of 100 mm and by 21 mm at a pretreatment VAS of 30 mm. If the primary symptom pretreatment VAS less than (<) 30 mm, then primary symptom relief was defined as 68% reduction from pretreatment. A VAS utilizes a scale consisting of a 100 millimeter (mm) horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The TOSR-P was calculated from the time of icatibant administration to the onset of primary symptom relief. (NCT03888755)
Timeframe: Baseline up to 120 hours post-treatment

InterventionHours (Median)
Icatibant1.07

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Time to Onset of Symptom Relief (TOSR)

The TOSR was defined as a 50 percent (%) reduction from the pre-treatment score in the 3-symptom composite VAS score for non-laryngeal attacks and 5-symptom composite VAS score for laryngeal attacks. A VAS utilizes a scale consisting of a 100 millimeter (mm) horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The participant should draw a vertical line at the point along the scale that represents the current status of the measured symptom. Composite VAS scores were calculated as the average of VAS measurements for skin swelling, skin pain, and abdominal pain (3-symptom composite) for non-laryngeal attacks and for skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change (5-symptom composite) for laryngeal attacks. (NCT03888755)
Timeframe: Baseline up to 120 hours post-treatment

InterventionHours (Median)
Icatibant1.75

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Composite Symptom Score (SS) Assessed by Participant

The participant-assessed composite symptom score was calculated as an average of abdominal pain, nausea, vomiting, diarrhea, skin pain, erythema, skin irritation, and skin swelling (8 symptoms) for non-laryngeal attacks and the average of abdominal pain, nausea, vomiting, diarrhea, skin pain, erythema,skin irritation, skin swelling, dysphagia and voice change (10 symptoms) for laryngeal attacks using the following 5-point scale 0 = none (absence of symptoms); 1 = mild (no to mild interference with daily activities); 2 = moderate (moderate interference with daily activities); 3 = severe (severe interference with daily activities); 4 = very severe (very severe interference with daily activities). Here the composite SS assessed by participant was reported. (NCT03888755)
Timeframe: 8 hours post dose

InterventionScore on a scale (Mean)
Icatibant0.14

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Investigator Global Assessment

"The investigator was made a global assessment (that is [i.e.] consideration of all abdominal symptoms combined, all cutaneous symptoms combined and/or all laryngeal symptoms combined) using the following 5-point scale, where the symptoms were scored from 0 for absence of symptoms to 4 for very severe: 0 = none (absence of symptoms); 1 = mild (no to mild interference with daily activities); 2 = moderate (moderate interference with daily activities); 3 = severe (severe interference with daily activities); 4 = very severe (very severe interference with daily activities)." (NCT03888755)
Timeframe: 2, 4 and 8 hours post dose

InterventionScore on a scale (Mean)
Cutaneous Symptoms: 2 hours (h) post doseCutaneous Symptoms: 4 h post doseCutaneous Symptoms: 8 h post doseAbdominal Symptoms: 2 h post doseAbdominal Symptoms: 4 h post doseAbdominal Symptoms: 8 h post doseLaryngeal Symptoms: 2 h post doseLaryngeal Symptoms: 4 h post doseLaryngeal Symptoms: 8 h post dose
Icatibant0.90.60.50.10.00.00.00.00.0

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Plasma Concentration for TAK-667

(NCT04654351)
Timeframe: Day 1 pre-dose and at multiple timepoints post-dose

Interventionug/l (Median)
Baseline (pre-dose)0.5 hours postdose1 hour postdose2 hours postdose4 hours postdose
TAK-667 10-30 mg0NANANANA

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Time to Initial Symptom Improvement Reported by Participant

Time to initial symptom improvement reported by participant, defined as the duration of time in hours from icatibant administration until the time when overall participant improvement was first noted by participant, participant's parent or participant's legal guardian. (NCT04654351)
Timeframe: Up to 8 hours post dose (or till the onset of HAE attacks were resolved)

Interventionhours (Median)
TAK-667 10-30 mgNA

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Time to Initial Symptom Improvement Reported by Investigator

Time to initial symptom improvement reported by investigator, was defined as the duration of time in hours from icatibant administration until the time when overall participant improvement was first noted by investigator. (NCT04654351)
Timeframe: Up to 8 hours post dose (or till the onset of HAE attacks were resolved)

Interventionhours (Median)
TAK-667 10-30 mgNA

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Number of Participants With Worsened Intensity of Clinical HAE Symptoms Between 2 and 4 Hours After Treatment With SC Icatibant Using Investigator-Rated Symptom Scores

Investigator-rated symptom score was used for assessment and scoring of cutaneous, abdominal, and laryngeal symptoms of acute HAE attacks related to daily activities. The score ranged from 0 to 4 and each number of scores means following; 0 = none; absence of symptoms, 1 = mild (no to mild interference with daily activities), 2 = moderate (moderate interference with daily activities), 3 = severe (severe interference with daily activities), 4 = very severe (very severe interference with daily activities). (NCT04654351)
Timeframe: From 2 hours post-dose to 4 hours post-dose

InterventionParticipants (Count of Participants)
TAK-667 10-30 mg0

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Number of Participants With Injection Site Reactions

Injection sites were examined for erythema, swelling, cutaneous pain, burning sensation, itching/pruritus, and warm sensation. Data for injection site reactions were collected separately from general reports of AEs. As pre-defined in the protocol, an injection site reaction not meeting SAE criteria was not required to be reported additionally as an AE. (NCT04654351)
Timeframe: Postdose, up to Day 8

Interventionpercentage of participants (Number)
TAK-667 10-30 mg2

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Number of Participants Who Were Treated With Rescue Medication During Study

Rescue medication included therapies for HAE used for HAE attack and symptomatic treatment used in order to improve symptoms of angioedema (eg, pain and nausea). (NCT04654351)
Timeframe: Up to approximately 6 months

InterventionParticipants (Count of Participants)
TAK-667 10-30 mg0

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Number of Participants Who Reported Presence of Anti-icatibant Antibodies

Serum samples for immunogenicity testing were collected for determination of anti-icatibant antibodies. If hypersensitivity was observed, it was reported as an AEs of special interest. An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. (NCT04654351)
Timeframe: Up to approximately 6 months

InterventionParticipants (Count of Participants)
TAK-667 10-30 mg0

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Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Events (TEAE)

An adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A treatment-emergent adverse event (TEAE) was defined as any adverse event occurring after the start of Icatibant administration of the treatment period. (NCT04654351)
Timeframe: Up to approximately 6 months

InterventionParticipants (Count of Participants)
TAK-667 10-30 mg0

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Time to Onset of Symptom Relief With Faces Pain Scale-Revised (FPS-R) Scores for Participants of 4 Years Age and Older

The time to onset of symptom relief, defined as the duration of time in hours from the time of icatibant administration to the earliest time at which the post-treatment score improved by at least 1 level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). (NCT04654351)
Timeframe: Baseline, and post dose on Day 1

Interventionhours (Median)
TAK-667 10-30 mgNA

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Time to Onset of Symptom Relief With Investigator-Rated Symptom Scores Assessed by Investigator

The time to onset of symptom relief, defined as the duration of time in hours from the time of icatibant administration to the earliest time at which at least a 20% improvement is observed in the average post-treatment score with no worsening of any single component score. Investigator-rated symptom score was used for assessment and scoring of cutaneous, abdominal, and laryngeal symptoms of acute HAE attacks related to daily activities. The score ranged from 0 to 4 and each number of scores meant the following: 0 = none; absence of symptoms, 1 = mild (no to mild interference with daily activities), 2 = moderate (moderate interference with daily activities), 3 = severe (severe interference with daily activities), 4 = very severe (very severe interference with daily activities). (NCT04654351)
Timeframe: Baseline, and post dose on Day 1

Interventionhours (Median)
TAK-667 10-30 mgNA

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Plasma Concentration for TAK-667 Metabolite M-I

(NCT04654351)
Timeframe: Day 1 pre-dose and at multiple timepoints post-dose

Interventionug/l (Median)
Baseline (pre-dose)0.5 hours postdose1 hour postdose2 hours postdose4 hours postdose
TAK-667 10-30 mg0NANANANA

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Plasma Concentration for TAK-667 Metabolite M-II

(NCT04654351)
Timeframe: Day 1 pre-dose and at multiple timepoints post-dose

Interventionug/l (Median)
Baseline (pre-dose)0.5 hours postdose1 hour postdose2 hours postdose4 hours postdose
TAK-667 10-30 mg0NANANANA

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