Claims for Patent: 10,449,146

Summary for Patent: 10,449,146

Title:	Methods of treating parkinson's disease by administration of apomorphine to an oral mucosa
Abstract:	Methods and pharmaceutical unit dosage forms for treating Parkinson's disease in a subject (e.g., an "off" episode in a subject having Parkinson's disease) are described. The pharmaceutical unit dosage forms are films having a first portion including particles containing an acid addition salt of apomorphine and a second portion containing a pH neutralizing agent. The pharmaceutical unit dosage forms can be flexible and have toughness greater than 100 g.times.mm. The methods can involve administering to a subject having Parkinson's disease a therapeutic dose sufficient to produce an apomorphine plasma concentrate of at least 2.64 ng/mL within 45 minutes after the administration. The subject may be identified as having low uptake, medium uptake, or high uptake of apomorphine administered via oral mucosa.
Inventor(s):	Barnhart; Scott David (York, PA), Koons; Michael Clinton (York, PA), Hariharan; Madhu Sudan (Greensboro, NC), Dubow; Jordan (Glencoe, IL), Bilbault; Thierry (Toronto, CA), Giovinazzo; Anthony John (Caledon, CA)
Assignee:	Sunovion Pharmaceuticals Inc. (Marlborough, MA)
Application Number:	15/789,528
Patent Claims:	1. A method of treating an "off" episode in a subject having Parkinson's disease, said method comprising: (a) providing a film having a first portion comprising apomorphine particles comprising an acid addition salt of apomorphine and a second portion comprising a pH neutralizing agent; (b) determining an effective dose of said film by up-titration of said subject; and (c) sublingually administering said effective dose of said film to said subject, wherein said effective dose of said film comprises an acid addition salt of apomorphine in an amount sufficient to produce, on average, following administration to the subject: (i) an apomorphine plasma concentration of at least 2.64 ng/mL within 30 minutes, and (ii) an apomorphine Cmax that is less than 10 ng/mL. 2. The method of claim 1, wherein the apomorphine T.sub.max is from 20 to 60 minutes following said sublingually administering said film to said subject. 3. The method of claim 1, wherein the film maintains an apomorphine plasma concentration of at least 2.64 ng/mL is maintained for a period of at least 60 minutes. 4. The method of claim 1, wherein said film has a toughness greater than or equal to 100 g .times. mm. 5. The method of claim 1, wherein said second portion comprises a permeation enhancer. 6. The method of claim 1, wherein said first portion comprises a permeation enhancer. 7. The method of claim 1, wherein said first portion is free of a permeation enhancer. 8. The method of claim 1, wherein said film comprises 20% (w/w) or more of a pharmaceutically acceptable high molecular weight polymer having a weight average molecular weight of 60 kDa or greater. 9. The method of claim 8, wherein said film comprises from 20% (w/w) to 40% (w/w) of said pharmaceutically acceptable high molecular weight polymer. 10. The method of claim 8, wherein said pharmaceutically acceptable high molecular weight polymer has a weight average molecular weight from 60kDa to 1,000 kDa. 11. The method of claim 1, wherein said film comprises 5% (w/w) or less of a pharmaceutically acceptable low molecular weight polymer having a weight average molecular weight of less than 60 kDa. 12. The method of claim 1, wherein said film disintegrates in aqueous media in 2 minutes or less. 13. The method of claim 1, wherein said film comprises 10 .+-.2.5 mg, 15 .+-.2.5 mg, 20.0 .+-.2.5 mg, 25.0 .+-.2.5 mg, 30.0 .+-.5.0 mg, or 35.0 .+-.5.0 mg of said acid addition salt of apomorphine.