TREATMENTS OF HEREDITARY ANGIOEDEMA
The present invention relates to treatments of hereditary angioedema (HAE). In particular, the present invention provides on-demand treatments of hereditary angioedema (HAE) by orally administering a plasma kallikrein inhibitor to a patient in need thereof on-demand.
1 . A method for treating an attack of hereditary angioedema (HAE) 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 treatment reduces the need for a second treatment of the HAE attack within 4 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof,
2 . The method according to claim 1 , wherein the treatment reduces the need for a second treatment of the HAE attack within 12 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
3 . The method according to claim 1 , wherein the treatment reduces the need for a second treatment of the HAE attack within 24 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
4 . The method according to claim 1 , wherein the treatment avoids the need for a second treatment of the HAE attack within 4 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
5 . The method according to claim 4 , wherein the treatment avoids the need for a second treatment of the HAE attack within 12 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
6 . The method according to claim 5 , wherein the treatment avoids the need for a second treatment of the HAE attack within 24 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
7 . The method according to claim 1 , wherein the patient is not administered a second treatment of the HAE attack within 4 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
8 . The method according to claim 7 , wherein the patient is not administered a second treatment of the HAE attack within 12 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
9 . The method according to claim 8 , wherein the patient is not administered a second treatment of the HAE attack within 24 hours of taking the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
10 . The method according to claim 1 , wherein the attack is resolved without administering a second treatment to the patient.
11 . A method for treating an attack of hereditary angioedema (HAE) 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 symptom relief of the attack starts within 3 hours of administering the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof,
12 . The method according to claim 11 , wherein “symptom relief” means that the attack is rated as “a little better” or higher for two consecutive time points when assessed according to the 7-point transition questions (7TQ).
13 . The method according to claim 12 , wherein the “two consecutive time points” are about 30 minutes apart.
14 . The method according to claim 11 , wherein the symptom relief of the attack starts between about 1.5 and 3.0 hours after administering the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
15 . A method for treating an attack of hereditary angioedema (HAE) 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 symptom relief of the attack starts between about 1.5 and 9 hours after administering the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof,
16 . The method according to claim 15 , wherein “symptom relief” means that a 50% reduction in composite VAS score occurred for three consecutive time points.
17 . The method according to claim 16 , wherein the “three consecutive time points” are about 30 minutes apart within 0-4 hours after administration of the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof and, if necessary, about 1 hour apart within 4-12 hours after administration of the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
18 . The method according to claim 15 , wherein the symptom relief of the attack starts between about 3 and 9 hours after administering the compound.
19 . A method for treating an attack of hereditary angioedema (HAE) 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 treatment halts the progress of the attack such that the symptoms of the attack do not worsen within a 12 hour period after administration of the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof,
20 . The method according to claim 19 , wherein “do not worsen” means that the attack did not worsen by one level or more on the 5LS within the 12 hours of administering the compound.
21 . The method according to claim 19 , wherein the treatment halts the progress of the attack such that the symptoms of the attack do not worsen within a 24 hour period after administration of the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof.
22 . The method according to claim 21 , wherein “do not worsen” means that the attack did not worsen by one level or more on the 5LS within the 24 hours of administering the compound.
23 . A method for treating an attack of hereditary angioedema (HAE) 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 treatment improves the severity of the attack to “none” (when assessed according to the 5LS),
24 . The method according to claim 23 , wherein the severity improves to “none” within 24 hours of administering the compound.
25 . The method according to claim 23 , wherein the severity improves to “none” within 12 hours of administering the compound.
26 . The method according to claim 23 , wherein the severity improves to “none” within 6 hours of administering the compound.
27 . The method according to claim 1 , wherein the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof is for use in treating an attack of hereditary angioedema (HAE) on-demand and is orally administered on-demand upon recognition of a symptom of an HAE attack.
28 . The method according to claim 27 , wherein the symptom of an 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; or mood changes.
29 . The method according to claim 28 , 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 an HAE attack being recognised.
30 . The method according to claim 29 , 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 an HAE attack being recognised.
31 . The method according to claim 30 , wherein the compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof is orally administered on-demand in the prodromal phase of an HAE attack.
32 . The method according to claim 31 , wherein the symptom recognised is at least one of: a slight swelling, abdominal pain or reddening of the skin.
33 . The method according to claim 31 , wherein the symptom recognised is Erythema marginatum.
34 . The method according to claim 1 , wherein the treatment shortens the duration of the HAE attack.
35 . The method according to claim 1 , wherein the compound or a pharmaceutically acceptable salt and/or solvate thereof is administered as an oral dosage form comprising: (i) the compound or a pharmaceutically acceptable salt and/or solvate thereof, and (ii) a pharmaceutically acceptable excipient.
36 . The method according to claim 35 , wherein the oral dosage form is a tablet comprising microcrystalline cellulose as a diluent, croscarmellose sodium as a disintegrant, polyvinyl pyrrolidone as a binder, and optionally magnesium stearate as a lubricant.
37 . The method according to claim 1 , wherein the patient is administered about 600 mg of the compound of formula A.
38 . The method according to claim 37 , wherein each dosage amount is administered as two tablets each comprising about 300 mg of the compound of formula A.