Solution comprising the chloride hydrochloride salt of 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-IUM-(fosnetupitant) and palonosetron hydrochloride in combination with dexamethasone as a neurokinin receptor modulator

Patent metadata

Field	Value
Publication number	US-10208073-B2
Application number	US-201815874325-A
Country	US
Kind code	B2
Filing date	Jan 18, 2018
Priority date	Nov 29, 2011
Publication date	Feb 19, 2019
Grant date	Feb 19, 2019

Abstract

Disclosed is a solution comprising the chloride hydrochloride salt of 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium (fosnetupitant) and palonosetron hydrochloride in combination with dexamethasone and its application in methods for preventing acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy.

First claim

What is claimed is:

1. A method for preventing acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy, comprising intravenously administering to the human patient, prior to the chemotherapy, a solution comprising a therapeutically effective amount of the chloride hydrochloride salt of fosnetupitant and a therapeutically effective amount of palonosetron hydrochloride, in combination with a therapeutically effective amount of dexamethasone.

2. The method of claim 1 , wherein the chloride hydrochloride salt of fosnetupitant is administered in an amount of from 150 mg to 200 mg based on the netupitant portion of the molecule and the palonosetron hydrochloride is administered in an amount of 0.25 mg based on the weight of the free base.

3. The method of claim 1 , wherein the solution has a concentration of from 2 mg/mL to 5 mg/mL of the chloride hydrochloride salt of fosnetupitant based on the weight of the netupitant portion of the molecule.

4. The method of claim 1 , wherein the solution has a concentration of from 5 mg/mL to 15 mg/mL of the chloride hydrochloride salt of fosnetupitant based on the weight of the netupitant portion of the molecule.

5. The method of claim 1 , wherein the chloride hydrochloride salt of fosnetupitant is administered in an amount of from 150 mg to 200 mg based on the netupitant portion of the molecule, the palonosetron hydrochloride is administered in an amount of 0.25 mg based on the weight of the free base, and the solution has a concentration of from 2 mg/mL to 5 mg/mL of the chloride hydrochloride salt of fosnetupitant based on the weight of the netupitant portion of the molecule.

6. The method of claim 1 , wherein the chloride hydrochloride salt of fosnetupitant is administered in an amount of from 150 mg to 200 mg based on the netupitant portion of the molecule, the palonosetron hydrochloride is administered in an amount of 0.25 mg based on the weight of the free base, and the solution has a concentration of from 5 mg/mL to 15 mg/mL of the chloride hydrochloride salt of fosnetupitant based on the weight of the netupitant portion of the molecule.

7. The method of claim 1 , wherein the therapeutically effective amount of dexamethasone comprises 12 mg administered orally on day 1, 8 mg administered orally on day 2, 8 mg administered orally on day 3 and 8 mg administered orally on day 4.

8. The method of claim 1 , wherein the method consists of intravenously administering to the human patient, prior to the chemotherapy, a solution comprising a therapeutically effective amount of the chloride hydrochloride salt of fosnetupitant and a therapeutically effective amount of palonosetron hydrochloride, in combination with a therapeutically effective amount of dexamethasone.

9. The method of claim 1 , wherein the fosnetupitant independently prevents acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy.

10. A method for preventing acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy, comprising intravenously administering to the human patient, prior to the chemotherapy, a solution comprising a therapeutically effective amount of the chloride hydrochloride salt of fosnetupitant and a therapeutically effective amount of palonosetron hydrochloride, in combination with a therapeutically effective amount of dexamethasone, wherein:
(a) the chloride hydrochloride salt of fosnetupitant is administered in an amount of from 150 mg to 200 mg based on the netupitant portion of the molecule;
(b) the palonosetron hydrochloride is administered in an amount of 0.25 mg based on the weight of the free base; and
(c) the solution has a concentration of from 2 mg/mL to 5 mg/mL of the chloride hydrochloride salt of fosnetupitant based on the weight of the netupitant portion of the molecule.

11. A method for preventing acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy, comprising intravenously administering to the human patient, prior to the chemotherapy, a solution comprising a therapeutically effective amount of the chloride hydrochloride salt of fosnetupitant and a therapeutically effective amount of palonosetron hydrochloride, in combination with a therapeutically effective amount of dexamethasone, wherein:
(a) the chloride hydrochloride salt of fosnetupitant is administered in an amount of from 150 mg to 200 mg based on the netupitant portion of the molecule;
(b) the palonosetron hydrochloride is administered in an amount of 0.25 mg based on the weight of the free base; and
(c) the solution has a concentration of from 5 mg/mL to 15 mg/mL of the chloride hydrochloride salt of fosnetupitant based on the weight of the netupitant portion of the molecule.

12. A method for preventing acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy, consisting of intravenously administering to the human patient, prior to the chemotherapy, a solution comprising a therapeutically effective amount of the chloride hydrochloride salt of fosnetupitant and a therapeutically effective amount of palonosetron hydrochloride, in combination with a therapeutically effective amount of dexamethasone, wherein:
(a) the chloride hydrochloride salt of fosnetupitant is administered in an amount of from 150 mg to 200 mg based on the netupitant portion of the molecule;
(b) the palonosetron hydrochloride is administered in an amount of 0.25 mg based on the weight of the free base;
(c) the solution has a concentration of from 2 mg/mL to 5 mg/mL of the chloride hydrochloride salt of fosnetupitant based on the weight of the netupitant portion of the molecule; and
(d) the therapeutically effective amount of dexamethasone comprises 12 mg administered orally on day 1, 8 mg administered orally on day 2, 8 mg administered orally on day 3 and 8 mg administered orally on day 4.

13. A method for preventing acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy, consisting of intravenously administering to the human patient, prior to the chemotherapy, a solution comprising a therapeutically effective amount of the chloride hydrochloride salt of fosnetupitant and a therapeutically effective amount of palonosetron hydrochloride, in combination with a therapeutically effective amount of dexamethasone, wherein:
(a) the chloride hydrochloride salt of fosnetupitant is administered in an amount of from 150 mg to 200 mg based on the netupitant portion of the molecule;
(b) the palonosetron hydrochloride is administered in an amount of 0.25 mg based on the weight of the free base;
(c) the solution has a concentration of from 5 mg/mL to 15 mg/mL of the chloride hydrochloride salt of fosnetupitant based on the weight of the netupitant portion of the molecule; and
(d) the therapeutically effective amount of dexamethasone comprises 12 mg administered orally on day 1, 8 mg administered orally on day 2, 8 mg administered orally on day 3 and 8 mg administered orally on day 4.

Assignees

• Helsinn Healthcare Sa

Inventors

• Fadini Luca
• Manini Peter
• Pietra Claudio
• Giuliano Claudio
• Lovati Emanuela
• Cannella Roberta
• Venturini Alessio
• Stella Valentino J

Classifications

• C07F9/025

  Purification; Separation; Stabilisation; Desodorisation of organo-phosphorus compounds (of natural phosphatides C07F9/103; phosphines C07F9/5095) · CPC title

• C07D213/76

  to which a second hetero atom is attached (nitro radicals C07D213/61) · CPC title

• A61K31/439

  the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) · CPC title

• A61K31/4178

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• A61P25/22

  Anxiolytics · CPC title