Pharmaceutical compositions for combination therapy

Abstract

This invention relates to novel pharmaceutical compositions comprising a therapeutically effective combination of a dopaminergic stabilizer known as Pridopidine, and an inhibitor of the vesicular monoamine transporter type 2 (VMAT) known as Tetrabenazine. The pharmaceutical compositions for use according to the invention are contemplated particularly useful for improving the symptomatic therapeutic effects, and for reducing the adverse effects, of Tetrabenazine in the treatment of movement disorders, and in particular movement disorders associated with Huntington's disease, Gilles de la Tourette's syndrome, or tardive dyskinesia.

Description

[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 783,730, filed Mar. 14, 2013, U.S. Provisional Application No. 61 / 625,192, filed Apr. 17, 2012, and U.S. Provisional Application No. 61 / 620,203, filed Apr. 4, 2012, the entire contents of which are hereby incorporated by reference herein.[0002]Throughout this application, various publications are referred to, and disclosures of these publications cited in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as of the date of the invention described herein.BACKGROUND OF THE INVENTION[0003]Pridopidine, i.e. 4-(3-Methanesulfonyl-phenyl)-1-propyl-piperidine, is a drug substance currently in clinical development for the treatment of Huntington's disease. This compound was first described in WO 01 / 46145.[0004]Pridopidine is a dopaminergic stabilizer that displays competitive dopamine D2 receptor antagonism with fast dissociation kinet...

AI Technical Summary

Benefits of technology

[0012]It has now surprisingly been found that Pridopidine is capable of reversing the behavioural inhibition caused by Tetrabenazine, while maintaining the primary pharmacological effect of Pridopidine, i.e. dopamine D2 receptor blockade. These findings suggest that coadministration of Pridopidine and Tetrabenazine would improve the therapeutically beneficial effects of Tetrabenazine, i.e. further alleviate involuntary movements, as well as reduced the adverse motor and affective effects.

Problems solved by technology

However, treatment with Tetrabenazine is associated with severe side effects.

Such side effects include parkinsonism, i.e. rigidity and impaired motor function, depression, and impaired functional capacity.

The administration of two drugs to treat a given condition, such as a movement disorder, raises a number of potential problems.

Thus, when two drugs are administered to treat the same condition, it is unpredictable whether each will complement, have no effect on, or interfere with, the therapeutic activity of the other in a human subject.

Not only may the interaction between two drugs affect the intended therapeutic activity of each drug, but the interaction may increase the levels of toxic metabolites (Guidance for Industry, 1999).

Hence, upon administration of two drugs to treat a disease, it is unpredictable what change will occur in the negative side profile of each drug.

In one example, the combination of natalizumab and interferon β-1a was observed to increase the risk of unanticipated side effects.

Additionally, it is difficult to accurately predict when the effects of the interaction between the two drugs will become manifest.

Therefore, the state of the art at the tame of filing is that the effects of combination therapy of two drugs, in particular Pridopidine and Tetrabenazine, cannot be predicted until the results of combination studies are available.

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