Claims for Patent: 10,342,800

Summary for Patent: 10,342,800

Title:	Dosing regimen for sedation with CNS 7056 (Remimazolam)
Abstract:	The invention relates to a dosing regimen for sedation with the fast-acting benzodiazepine CNS 7056 in combination with an opioid, in particular fentanyl, whereas CNS 7056 is given in a dose of 2 to 20 mg, preferably between 4 and 9 mg and most preferably between 5 and 8 mg.
Inventor(s):	Karin Wilhelm-Ogunbiyi, Keith Borkett, Gary Stuart Tilbrook, Hugh Wiltshire
Assignee:	Paion UK Ltd
Application Number:	US16/213,879
Patent Claims:	1. A method for inducing general anaesthesia in a subject, comprising administering to the subject: (a) 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic acid methyl ester of formula (I) or a pharmaceutically acceptable salt thereof, in an amount sufficient to induce general anaesthesia in the subject; and (b) an analgesic drug; and wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, administered to the subject does not depend on the body weight of the subject. 2. The method of claim 1, further comprising maintaining general anaesthesia in the subject by administering to the subject a further amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, and an analgesic drug, wherein the further amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, administered to the subject does not depend on the body weight of the subject. 3. The method of claim 2, wherein the duration of general anaesthesia in the subject is less than one hour. 4. The method of claim 2, further comprising maintaining a patient airway or positive pressure ventilation in the subject. 5. The method of claim 1, wherein the analgesic drug is an opioid. 6. The method of claim 5, wherein the amount of the opioid administered to the subject does not depend on the body weight of the subject. 7. The method of claim 5, wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, and the opioid are intravenously administered to the subject. 8. The method of claim 5, wherein the opioid is selected from the group consisting of fentanyl, alfentanil, carfentanil, lofentanil, remifentanil, sufentanil, thiofentanyl, α-methylthiofentanyl, α-methylacetylfentanyl, α-methylfentanyl, ohmefentanyl, β-hydroxy-fentanyl, parafluorfentanyl, and 3-methylfentanyl, or a salt thereof. 9. The method of claim 8, wherein the opioid is remifentanil, or a salt thereof. 10. A method for inducing loss of consciousness in a subject, comprising administering to the subject: (a) 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic acid methyl ester of formula (I) or a pharmaceutically acceptable salt thereof, in an amount sufficient to induce loss of consciousness in the subject; and (b) an analgesic drug; and wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, administered to the subject does not depend on the body weight of the subject. 11. The method of claim 10, further comprising maintaining loss of consciousness in the subject by administering to the subject a further amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, and an analgesic drug, wherein the further amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, administered to the subject does not depend on the body weight of the subject. 12. The method of claim 11, wherein the duration of loss of consciousness in the subject is less than one hour. 13. The method of claim 11, further comprising maintaining a patient airway or positive pressure ventilation in the subject. 14. The method of claim 10, wherein the analgesic drug is an opioid. 15. The method of claim 14, wherein the amount of the opioid administered to the subject does not depend on the body weight of the subject. 16. The method of claim 14, wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, and the opioid are intravenously administered to the subject. 17. The method of claim 14, wherein the opioid is selected from the group consisting of fentanyl, alfentanil, carfentanil, lofentanil, remifentanil, sufentanil, thiofentanyl, α-methylthiofentanyl, α-methylacetylfentanyl, α-methylfentanyl, ohmefentanyl, β-hydroxy-fentanyl, parafluorfentanyl, and 3-methylfentanyl, or a salt thereof. 18. The method of claim 17, wherein the opioid is remifentanil, or a salt thereof. 19. A method for the induction and maintenance of procedural sedation in a subject, comprising intravenously administering to the subject an initial dose of from about 2 mg to about 10 mg of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester, or a pharmaceutically acceptable salt thereof, over a one minute time period, wherein the amount of the initial dose does not depend on the body weight of the subject. 20. The method of claim 19, wherein the subject is 18 years or older. 21. The method of claim 19, further comprising administering to the subject one or more supplemental doses of from about 2 mg to about 10 mg of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester, or a pharmaceutically acceptable salt thereof, over a 15-second time period, wherein the amount of each of the one or more supplemental doses does not depend on the body weight of the subject. 22. The method of claim 21, wherein the one or more supplemental doses of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester, or a pharmaceutically acceptable salt thereof, is administered to the subject not less than four minutes following administration of the initial dose or a prior supplemental dose. 23. The method of claim 22, wherein the one or more supplemental doses of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester, or a pharmaceutically acceptable salt thereof, is administered to the subject not less than three minutes following administration of the initial dose or a prior supplemental dose. 24. The method of claim 22, wherein the one or more supplemental doses of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester, or a pharmaceutically acceptable salt thereof, is administered to the subject not less than two minutes following administration of the initial dose or a prior supplemental dose. 25. The method of claim 19, wherein a dose of an opioid is administered to the subject prior to the initial dose of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester, or a pharmaceutically acceptable salt thereof. 26. The method of claim 25, wherein the opioid is fentanyl, or a salt thereof. 27. The method of claim 21, wherein the amount of the one or more supplemental doses of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester, or a pharmaceutically acceptable salt thereof, administered to the subject is adjusted based on the level of sedation in the subject. 28. The method of claim 27, wherein the amount of the one or more supplemental doses of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester, or a pharmaceutically acceptable salt thereof, administered to the subject is adjusted to induce and maintain the subject in a state of mild to moderate sedation.