Compositions and methods for treating centrally mediated nausea and vomiting

11559,523

17/075757

October 21, 2020

Provided are compositions and methods for treating or preventing nausea and vomiting in patients undergoing chemotherapy, radiotherapy, or surgery.

Helsinn Healthcare S.A. (Lugano / Pazzallo, CH)

Helsinn Healthcare SA (Lugano/Pazzallo, CH)

1. A method of treating emesis in a patient in need thereof comprising orally administering to said patient a solid oral dosage form comprising a combination of a therapeutically effective amount of palonosetron or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of netupitant or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein said emesis is induced by cancer chemotherapy or radiotherapy.

3. The method of claim 1 , wherein the emesis is induced by highly emetogenic or moderately emetogenic chemotherapy.

4. The method of claim 1 , wherein said treating comprises preventing said emesis.

5. The method of claim 1 , further comprising administering chemotherapy to said patient after said solid oral dosage form, wherein said solid oral dosage form is administered no more than two hours before said chemotherapy.

6. The method of claim 1 , wherein said therapeutically effective amounts comprise from 100 to 300 mg of netupitant and 0.5 mg of palonosetron hydrochloride based on the weight of the free base.

7. The method of claim 1 , wherein said therapeutically effective amounts comprise 300 mg of netupitant and 0.5 mg of palonosetron hydrochloride based on the weight of the free base.

8. A method of treating delayed-onset emesis in a patient in need thereof comprising orally administering to said patient a solid oral dosage form comprising a combination of a therapeutically effective amount of palonosetron or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of netupitant or a pharmaceutically acceptable salt thereof.

9. The method of claim 8 , wherein said emesis is induced by cancer chemotherapy or radiotherapy.

10. The method of claim 8 , wherein the emesis is induced by highly emetogenic or moderately emetogenic chemotherapy.

11. The method of claim 8 , wherein said treating comprises preventing said emesis.

12. The method of claim 8 , further comprising administering chemotherapy to said patient after said solid oral dosage form, wherein said solid oral dosage form is administered no more than two hours before said chemotherapy.

13. The method of claim 8 , wherein said therapeutically effective amounts comprise from 100 to 300 mg of netupitant and 0.5 mg of palonosetron hydrochloride based on the weight of the free base.

14. The method of claim 8 , wherein said therapeutically effective amounts comprise 300 mg of netupitant and 0.5 mg of palonosetron hydrochloride based on the weight of the free base.

15. An orally administered dosage form comprising a combination of a therapeutically effective amount of palonosetron or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of netupitant or a pharmaceutically acceptable salt thereof.

16. The dosage form of claim 15 , wherein said therapeutically effective amounts are effective to treat emesis induced by cancer chemotherapy or radiotherapy.

17. The dosage form of claim 15 , wherein said therapeutically effective amounts comprise from 100 to 300 mg of netupitant and 0.5 mg of palonosetron hydrochloride based on the weight of the free base.

18. The dosage form of claim 15 , wherein said therapeutically effective amounts comprise 300 mg of netupitant and 0.5 mg of palonosetron hydrochloride based on the weight of the free base.

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Exhibit D1: Sergio Poli-Bigelli et all. “Addition of the Neurokinin 1 Receptor Antagonist Aprepitant to Standard Antiemetic Therapy Improves Control of Chemotherapy-Induced Nausea and Vomiting (CINV)” published on Jun. 15, 2003; 9 pages. cited by applicant
Exhibit D2: Hoffmann T et. all. “Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists” published on Dec. 5, 2005; 4 pages. cited by applicant
Exhibit D3: Goldhill John, “Advances in drug discovery” published on Feb. 23, 2006; 4 pages. cited by applicant
Exhibit D4: Reddy K et al., “Novel Neurokinin-1 Antagonists as antiemetic for the treatment of Chemotherapy induced Emesis” published on Apr. 2006; 3 pages. cited by applicant
Exhibit D6: Grunberg S.M, et. al, “A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy” published on Jun. 9, 2006; 9 pages. cited by applicant
Exhibit D7: Strausz J, Rolski J, Aziz Z, et al. “Phase III results for the novel neurokinin-1 (NK1) receptor antagonist, casopitant: Single oral dosing regimen for chemotherapy-induced nausea and vomiting (CINV) in patients (Pts) receiving Highly Emetogenic Chemotherapy (HEC)”. J Clin Oncol. 2008; 2 pages. cited by applicant
Exhibit D8: Jon D. Herrington, et al., “Randomized, Placebo-controlled, Pilot Study Evaluating Aprepitant Single Dose Plus Palonosetron and Dexamethasone for the Prevention of Acute and Delayed Chemotherapy-induced Nausea and Vomiting” published on Mar. 7, 2008; 8 pages. cited by applicant
Exhibit D9: Steven M. Grunberg et al., “Effectiveness of a single-day three-drug regimen of Dexamethasone, Palonosetron, and Aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy” published on Nov. 27, 2008; 6 pages. cited by applicant
Exhibit D10: Christina Ruhlmann, “Casopitant: a novel NK1-receptor antagonist in the prevention of chemotherapy-induced nausea and vomiting” published on May 8, 2009; 10 pages. cited by applicant
Exhibit D11: Steven M. Grunberg et al., “Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial” published on May 11, 2009; 10 pages. cited by applicant
Exhibit D12: P. Diemunsch, et al., “Neurokinin-1 receptor antagonists in the prevention of postoperative nausea and vomiting” published on May 19, 2009; 7 pages. cited by applicant
Exhibit D13: Jorn Herrstedt et al., “Phase III Trial of Casopitant, a Novel Neurokinin-1 Receptor Antagonist, for the Prevention of Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy” published on Oct. 5, 2009; 7 pages. cited by applicant
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