JPWO2020064748A5 - - Google Patents

Claims (30)

An inhalable pharmaceutical composition comprising ketamine or a pharmaceutically acceptable salt thereof for use in a method of treating depression by administering the composition to the lungs via a pulmonary route, wherein The treatment comprises a plurality of sequences of cycles of administration by inhalation, the cycles lasting from 10 to 30 days, wherein each of the plurality of sequences of administration occurs on a single day, with 2 to 2 in between sequences. Said pharmaceutical composition, having an interval of 4 days and each of said sequences consisting of multiple single-dose inhalations separated by rest periods lasting at least 5 minutes. 2. The composition for use according to claim 1, wherein the composition is an inhalable dry powder composition. 3. The composition for use according to claim 1 or 2, wherein the pharmaceutically acceptable salt is the hydrochloride. A composition for use according to any one of claims 1 to 3, wherein the ketamine is esketamine hydrochloride. A composition for use according to any one of claims 1 to 4, wherein the composition comprises 2 mg to 100 mg of micronized ketamine calculated as the free base per nominal unit dose. A composition for use according to claim 5, wherein the composition comprises 2 mg to 40 mg, preferably 2 to 20 mg, of micronized esketamine calculated as free base per nominal unit dose. 7. The composition for use according to claim 6, wherein the composition formulation comprises 4 mg of micronized esketamine calculated as the free base per nominal unit dose. The inhalable dry powder composition contains one or more selected from the group consisting of a carbohydrate extender in an amount of 30-95% by weight and a stabilizer in an amount of 0.2-3% by weight, relative to the total weight of the composition. A composition for use according to any one of claims 2 to 7, comprising an additive of 9. The dry powder composition of any of claims 2-8, wherein the dry powder composition comprises ketamine having a median particle size d50 of 1-10 μm, d10 of 0.2-5 μm and d90 of 3-35 μm, as measured by a laser diffraction technique. or a composition for use according to claim 1. For use according to any one of claims 5 to 9, wherein the composition provides an emitted dose of at least 1.0 mg ketamine calculated as free base, corresponding to 1.2 mg ketamine hydrochloride. composition. 11. The composition for use according to claim 10, wherein the fraction of the emitted dose delivered to the lung is at least 40%. A composition for use according to any one of claims 2 to 11, wherein the composition is incorporated into pre-weighed and individually sealed blisters having a plurality of individual nominal unit doses. A composition for use according to any one of claims 2 to 11, wherein the composition is incorporated into a capsule having a single nominal unit dose. A composition for use according to any preceding claim, wherein the composition for administration via the pulmonary route is contained in a multi-dose powder reservoir. The composition for use according to any one of the preceding claims, wherein said cycle lasts 12-14 days and comprises 4 sequences of administration separated by intervals of 3-4 days. Use of ketamine or a pharmaceutically acceptable salt thereof in the manufacture of an inhalable pharmaceutical composition for the treatment of depression by pulmonary administration via a pulmonary route , wherein said treatment comprises a plurality of a sequence of cycles of administration by inhalation, the cycle lasting 10 to 30 days, wherein each of the plurality of sequences of administration occurs on a single day, with intervals of 2 to 4 days between sequences; and each of said sequences consists of multiple single-dose inhalations separated by rest periods lasting at least 5 minutes. 17. Use according to claim 16, wherein the composition is an inhalable dry powder composition. 18. Use according to claim 16 or 17, wherein the pharmaceutically acceptable salt is hydrochloride. Use according to any one of claims 16-18, wherein the ketamine is esketamine hydrochloride. Use according to any one of claims 16 to 19, wherein the composition comprises 2 mg to 100 mg micronized ketamine calculated as the free base per nominal unit dose. Use according to claim 20, wherein the composition comprises 2 mg to 40 mg, preferably 2 to 20 mg, of micronized esketamine calculated as free base per nominal unit dose. 22. Use according to claim 21, wherein the composition formulation comprises 4 mg of micronized esketamine calculated as the free base per nominal unit dose. The inhalable dry powder composition contains one or more selected from the group consisting of a carbohydrate extender in an amount of 30-95% by weight and a stabilizer in an amount of 0.2-3% by weight, relative to the total weight of the composition. Use according to any one of claims 17 to 22, comprising an additive of 24. The dry powder composition of any of claims 17-23, wherein the dry powder composition comprises ketamine having a median particle size d50 of 1-10 μm, d10 of 0.2-5 μm and d90 of 3-35 μm, as measured by a laser diffraction technique. or the use described in paragraph 1. Use according to any one of claims 20 to 24, wherein the composition provides an emitted dose of at least 1.0 mg ketamine, calculated as the free base corresponding to 1.2 mg ketamine hydrochloride. 26. Use according to claim 25, wherein the fraction of the emitted dose delivered to the lung is at least 40%. Use according to any one of claims 17 to 26, wherein the composition is incorporated into pre-weighed and individually sealed blisters having a plurality of individual nominal unit doses. Use according to any one of claims 17 to 26, wherein the composition is incorporated into a capsule having a single nominal unit dose. Use according to any one of claims 16 to 26, wherein the composition for administration via the pulmonary route is contained in a multi-dose powder reservoir. Use according to any one of claims 16-29, wherein the cycle lasts 12-14 days and comprises 4 sequences of administration separated by intervals of 3-4 days.