Acamprosate formulations, methods of using the same, and combinations comprising the same
Inventors
Fogel, Barry S. • Kerns, William D. • Fong, Kei-Lai • Chow, San-Laung • Lin, Edward • Wong, David
Assignees
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Publication Number
US-9427420-B2
Publication Date
2016-08-30
Expiration Date
Abstract
Embodiments disclosed herein generally relate to acamprosate formulations, methods of use of the formulations, to methods of using the formulations in combination with at least one other medication, and to combination products and compositions comprising the formulations and at least one other medication, such as neuroleptic (antipsychotic) and/or antidepressant drugs.
Core Innovation
The patent discloses gastric-retentive controlled-release (GR-CR) acamprosate formulations that alter pharmacokinetics by maintaining plasma concentration above a therapeutic threshold for only part of the day while using total daily doses below 1 g and once- or twice-daily dosing. The disclosure reports that GR-CR acamprosate can lower Cmax and increase residence time above threshold concentrations compared with immediate-release formulations in a dog pharmacokinetic model.
The patent links the GR-CR pharmacokinetic profile to treatment rationales for neuropsychiatric disorders, including tardive dyskinesia, and emphasizes maintaining concentration relative to a threshold blood level. The disclosure further states that GR-CR can improve residence time above threshold concentrations for only a portion of the day.
The patent also discloses fixed-dose combination products that pair sub-gram GR-CR acamprosate with neuroleptics, including first- or second-generation neuroleptics, and can additionally include SSRIs/SNRIs and optionally metoclopramide. The stated purpose is to reduce TD risk and metabolic side effects while improving anxiety/agitation, and the disclosure further includes using a fed-mode inducing agent, particularly alpha-lipoic acid including enantiomers, to increase gastric retention and enable empty-stomach dosing.
Claims Coverage
The provided independent claims cover both a method of administering a specific tablet formulation and the tablet formulation itself. Across the independent claims, the claims are centered on a fixed composition of acamprosate calcium or other pharmaceutically acceptable acamprosate salt within a polymer matrix comprising carbomer homopolymer type B at a specified amount, together with inclusion of a neuroleptic; one dependent claim further narrows the target neuropsychiatric disorders.
Acamprosate in fixed carbomer homopolymer type B polymer matrix with neuroleptic
A tablet comprising 800 mg of acamprosate calcium or other pharmaceutically acceptable salt of acamprosate, distributed within a polymer matrix that comprises or consists of 60 mg of carbomer homopolymer type B, wherein the tablet further comprises a neuroleptic.
Neuropsychiatric disorder subset for acamprosate/neuroleptic use
The subject is suffering from a neuropsychiatric disorder selected from schizophrenia, bipolar disorder, Tourette Syndrome, and tardive dyskinesia.
Tablet formulation of acamprosate/neuroleptic with specified carbomer homopolymer type B amount
A tablet comprising 800 mg acamprosate calcium or other pharmaceutically acceptable salt of acamprosate, distributed within a polymer matrix that comprises or consists of 60 mg of carbomer homopolymer type B, wherein the tablet further comprises a neuroleptic.
Overall, the claim coverage is directed to a specific GR-CR acamprosate tablet composition in which acamprosate calcium or another pharmaceutically acceptable salt is distributed in a polymer matrix containing carbomer homopolymer type B at 60 mg, combined with a neuroleptic; dependent coverage further specifies a set of neuropsychiatric disorders.
Stated Advantages
The patent claims that GR-CR acamprosate can lower Cmax and increase residence time above therapeutic threshold concentrations compared with immediate-release in a dog PK model.
The patent states that combination products aim to reduce TD risk and metabolic side effects while improving anxiety/agitation.
Documented Applications
Treatment rationales for neuropsychiatric disorders including tardive dyskinesia (TD).
Use of fixed-dose combination products pairing sub-gram GR-CR acamprosate with neuroleptics, and optionally including SSRIs/SNRIs and optionally metoclopramide, directed to reducing TD risk and metabolic side effects while improving anxiety/agitation.
Use of fed-mode inducing agent, especially alpha-lipoic acid including enantiomers, to increase gastric retention and enable empty-stomach dosing.
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