Osmotic dosage forms comprising deutetrabenazine and methods of use thereof
Provided herein are osmotic dosage forms containing deutetrabenazine for use in the treatment of, e.g., hyperkinetic movement disorders. When orally administered to a subject on a once-daily basis, the dosage forms provide a favorable pharmacokinetic profile for the active agent indicating treatment efficacy over an extended period of time.
1 . A method of transitioning a human subject being treated with a total daily dose of deutetrabenazine twice daily (bid) to the total daily dose as a deutetrabenazine once daily for control of abnormal involuntary movement, comprising:
a) administering to the human subject a last dose of the deutetrabenazine twice daily; and
b) the next day, administering to the human subject the total daily dose as a deutetrabenazine once daily osmotic dosage form, wherein the osmotic dosage form comprises:
a. a tablet core comprising an active layer and a push layer, wherein the active layer comprises an amount of deutetrabenazine microparticles and an active layer control release agent, and wherein the push layer comprises an osmotic agent and a push layer control release agent, and an optional tablet seal coat on the outer surface of the tablet core;
b. a semipermeable layer surrounding the tablet core;
c. a port extending through the semipermeable layer into the tablet core; and
d. an immediate release coating external to the semipermeable layer comprising a second amount of deutetrabenazine microparticles,
wherein the dosage comprises from about 6 mg to about 48 mg deutetrabenazine in the form of deutetrabenazine microparticles and wherein about 70%-80% of the total amount of deutetrabenazine microparticles present in the dosage form is present within the active layer and wherein about 20%-30% of the total amount of deutetrabenazine microparticles present in the dosage form, is present within the immediate release coating;
wherein the deutetrabenazine microparticles have a D 90 of 15 μm, a D 50 10 μm, and/or a D 10 of 3 μm, and
wherein the control of the abnormal involuntary movement is maintained during the transitioning from the last dose of deutetrabenazine twice daily to the deutetrabenazine once daily osmotic dosage form.
2 . The method of claim 1 , wherein the total daily dose of deutetrabenazine is from 12 mg to 48 mg; or 12 mg; or 18 mg; or 24 mg; or 30 mg; or 36 mg; or 42 mg; or 48 mg.
3 . The method of claim 1 , wherein the abnormal involuntary movement is chorea, akathisia, dyskinesia, tremor, tic, chorea associated with Huntington's disease, tardive dyskinesia, a tic associated with Tourette syndrome, Parkinson's disease levodopa-induced dyskinesia, or dyskinesia in cerebral palsy.
4 . The method of claim 1 , wherein the total daily dose of deutetrabenazine once daily is administered with or without food.
5 . A method of transitioning a human subject being treated with a daily amount of tetrabenazine to a once daily amount of deutetrabenazine, for control of abnormal involuntary movement from, comprising:
a) administering the last dose of tetrabenazine; and
b) the next day, administering to the subject a once daily deutetrabenazine osmotic dosage form, wherein the control of the abnormal involuntary movement is maintained during the transitioning from the last dose of tetrabenazine to the once daily deutetrabenazine dosage form
wherein the daily amount of tetrabenazine is 25 mg and the once daily amount of deutetrabenazine is 12 mg; or
wherein the daily amount of tetrabenazine is 37.5 mg and the once daily amount of deutetrabenazine is 18 mg; or
wherein the daily amount of tetrabenazine is 50 mg and the once daily amount of deutetrabenazine is 24 mg; or
wherein the daily amount of tetrabenazine is 62.5 mg and the once daily amount of deutetrabenazine is 30 mg; or
wherein the daily amount of tetrabenazine is 75 mg and the once daily amount of deutetrabenazine is 36 mg; or
wherein the daily amount of tetrabenazine is 87.5 mg and the once daily amount of deutetrabenazine is 42 mg; or
wherein the daily amount of tetrabenazine is 100 mg and the once daily amount of deutetrabenazine is 48 mg;
and
wherein the osmotic dosage form comprises:
a. a tablet core comprising an active layer and a push layer, wherein the active layer comprises an amount of deutetrabenazine microparticles and an active layer control release agent, and wherein the push layer comprises an osmotic agent and a push layer control release agent, and an optional tablet seal coat on the outer surface of the tablet core;
b. a semipermeable layer surrounding the tablet core;
c. a port extending through the semipermeable layer into the tablet core; and
d. an immediate release coating external to the semipermeable layer comprising a second amount of deutetrabenazine microparticles,
wherein the dosage comprises from about 6 mg to about 48 mg deutetrabenazine in the form of deutetrabenazine microparticles and wherein about 70%-80% of the total amount of deutetrabenazine microparticles present in the dosage form is present within the active layer and wherein about 20%-30% of the total amount of deutetrabenazine microparticles present in the dosage form, is present within the immediate release coating, and
wherein the deutetrabenazine microparticles have a D 90 of 15 μm, a D 50 10 μm, and/or a D 10 of 3 μm.
6 . The method of claim 5 , wherein the abnormal involuntary movement is chorea, akathisia, dyskinesia, tremor, tic, chorea associated with Huntington's disease, tardive dyskinesia, a tic associated with Tourette syndrome, Parkinson's disease levodopa-induced dyskinesia or dyskinesia in cerebral palsy.
7 . The method of claim 5 , wherein the once daily deutetrabenazine dosage form, is administered with or without food.