TREATMENTS OF ANGIOEDEMA
The present invention relates to treatments of bradykinin-mediated angioedema. In particular, the present invention provides on-demand treatments of bradykinin-mediated angioedema by orally administering a plasma kallikrein inhibitor to a patient in need thereof on-demand as an oral dosage form particularly suitable for patients who may struggle to swallow tablets.
1 - 42 . (canceled)
43 . A method for treating bradykinin mediated angioedema on-demand comprising: orally administering the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is administered as an oral dosage form that is a chewable tablet or soft gel, a mini-tablet, a powder, granules, a solution, an emulsion, a suspension, a syrup, a dispersible tablet, or an orodispersible tablet, wherein the compound of Formula A is:
44 . (canceled)
45 . (canceled)
46 . The method according to claim 43 , wherein the bradykinin mediated angioedema is hereditary angioedema (HAE); or wherein the bradykinin mediated angioedema is bradykinin-mediated angioedema non-hereditary (BK-AEnH).
47 . The method according to claim 46 , wherein the bradykinin mediated angioedema is hereditary angioedema (HAE).
48 . The method according to claim 46 , wherein the bradykinin mediated angioedema is bradykinin-mediated angioedema non-hereditary (BK-AEnH).
49 . The method according to claim 48 , wherein the bradykinin-mediated angioedema non-hereditary (BK-AEnH) is not caused by an inherited genetic dysfunction, fault, or mutation.
50 . The method according to claim 49 , wherein the BK-AEnH is: non-hereditary angioedema with normal C1 Inhibitor (AE-nC1 Inh), optionally environmental, hormonal, or drug-induced; acquired angioedema; anaphylaxis associated angioedema; angiotensin converting enzyme (ACE) inhibitor-induced angioedema; dipeptidyl peptidase-4 inhibitor-induced angioedema; and tPA-induced angioedema (tissue plasminogen activator-induced angioedema).
51 . The method according to claim 49 , wherein the AE-nC1 Inh is environmentally-induced by air pollution and/or silver nanoparticles.
52 . The method according to claim 43 , wherein the patient is aged between 2 and less than 18.
53 . The method according to claim 52 , wherein the patient is aged between 2 and less than 12.
54 . The method according to claim 43 , wherein the patient is aged 70 years or older.
55 . The method according to claim 43 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is for use in treating an attack of bradykinin mediated angioedema on-demand and is orally administered on-demand upon recognition of a symptom of a bradykinin mediated angioedema attack.
56 . The method according to claim 55 , wherein the patient is suffering from a laryngeal attack.
57 . The method according to claim 55 , wherein the symptom of an acute HAE attack recognised is at least one of: swelling of tissues; fatigue; headache; muscle aches; skin tingling; abdominal pain; nausea; vomiting; diarrhoea; difficulty swallowing; hoarseness; shortness of breath; and/or mood changes.
58 . The method according to claim 55 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is orally administered on-demand within 1 hour of the symptom of a bradykinin mediated angioedema attack being recognised.
59 . The method according to claim 55 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is orally administered on-demand within 30 minutes, within 20 minutes, within 10 minutes, or within 5 minutes of the symptom of a bradykinin mediated angioedema attack being recognised.
60 . The method according to claim 55 , wherein the compound of Formula A (or a pharmaceutically acceptable salt or solvate thereof) is orally administered on-demand in the prodromal phase of a bradykinin mediated angioedema attack.
61 . The method according to claim 60 , wherein the symptom recognised is at least one of: a slight swelling, abdominal pain or reddening of the skin.
62 . The method according to claim 61 , wherein the symptom recognised is erythema marginatum.
63 . The method according to claim 43 , wherein the treatment shortens the duration of the bradykinin mediated angioedema attack.
64 . The method according to claim 60 , wherein the treatment prevents the bradykinin mediated angioedema attack from progressing to the swelling stage of a bradykinin mediated angioedema attack.
65 . The method according to claim 43 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is orally administered on-demand to prophylactically reduce the likelihood of a bradykinin mediated angioedema attack.
66 . The method according to claim 65 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is orally administered on-demand when it is anticipated that a bradykinin mediated angioedema attack will be induced.
67 . The method according to claim 65 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is orally administered on-demand to prevent a bradykinin mediated angioedema attack.
68 . The method according to claim 65 , wherein the BK-AEnH is tPA-induced angioedema, wherein the patient is also being administered a tissue plasminogen activator, wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is administered prior to, during, or after administration of the tissue plasminogen activator to the patient.
69 . The method according to claim 66 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is orally administered on-demand when it is anticipated that a bradykinin mediated angioedema attack will be induced by physical traumata and/or stress.
70 . The method according to claim 69 , wherein it is anticipated that a bradykinin mediated angioedema attack will be induced by the physical traumata of a dental procedure and/or the mental stress associated with a dental procedure.
71 . The method according to claim 43 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is administered as a dispersible tablet or an orodispersible tablet.
72 . The method according to claim 71 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is administered as a dispersible tablet.
73 . The method according to claim 72 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is administered as an orodispersible tablet.
74 . The method according to claim 73 , wherein the orodispersible tablet comprises one or more of microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium, camphor, sodium saccharin, and magnesium stearate.
75 . The method according to claim 73 , wherein the orodispersible tablet comprises polyvinyl polypyrrolidone.
76 . The method according to claim 73 , wherein the orodispersible tablet comprises one or more of pearlitol Flash (co-processed Mannitol/Maize starch), sucralose, and sodium stearyl fumarate.
77 . The method according to claim 43 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is administered as a mini-tablet.
78 . The method according to claim 77 , wherein the mini-tablet comprises one or more of microcrystalline cellulose, croscarmellose sodium, polyvinylpyrrolidone (povidone), and magnesium stearate.
79 . The method according to claim 43 , wherein the compound of Formula A (or a pharmaceutically acceptable salt and/or solvate thereof) is administered as a orodispersible film.
80 . The method according to claim 71 , wherein the disintegration specification is >80% in less than about 10 minutes.
81 . The method according to claim 80 , wherein the disintegration specification is >80% in less than about 1 minute.
82 . The method according to claim 71 , wherein the dissolution specification is ≥80% in less than about 45 minutes.
83 . The method according to claim 82 , wherein the dissolution specification is >80% in less than about 5 minutes.
84 . The method according to claim 75 , wherein the polyvinyl polypyrrolidone is crospovidone.