Formulations of T-type calcium channel modulators and methods of use thereof
Inventors
Reddy, Kiran • Lee, Margaret S. • BELFORT, Gabriel Maurice • GARAD, Sapna Makhija • Padval, Mahesh • Wagner, Randall • Wittmann, Marion
Assignees
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Publication Number
US-12077502-B2
Publication Date
2024-09-03
Expiration Date
Abstract
Described herein, in part, are dosage forms and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a T-type calcium channel, such as epilepsy and epilepsy syndromes (e.g., absence seizures, juvenile myoclonic epilepsy, or a genetic epilepsy), tremor (e.g., essential tremor), and psychiatric disorder (e.g., mood disorders (e.g., major depressive disorder)). The present invention further comprises methods for modulating the function of a T-type calcium channel.
Core Innovation
The invention relates to T-type calcium channel modulator pharmaceutical compositions and oral modified-release dosage forms. The compositions include a compound of Formula (I) and/or a compound of Formula (II) and use release-modifying excipients and polymers in modified-release formulations. Crystalline solid-state forms are characterized using X-ray powder diffraction (XRPD), with specified diffraction peak sets for the crystalline anhydrous Form C hydrochloride of Formula (II).
A key aspect is the oral modified-release strategy that uses a modified-release polymer to shape exposure and dosing behavior, including approaches described to reduce Cmax and shift Tmax versus immediate-release. The crystalline anhydrous Form C hydrochloride of Formula (II) is further supported by solid-state characterization including thermal properties such as DSC, thermal decomposition and weight loss via TGA, and melting behavior. The XRPD-defined solid form is linked to the modified-release oral dosage form for treating neurological conditions, including essential tremor.
The disclosed therapeutic use includes treating essential tremor using an oral dosage form comprising the crystalline anhydrous Form C hydrochloride of Formula (II) and a modified-release polymer. Stated evaluation and endpoints include tremor assessment using The Essential Tremor Rating Assessment Scale (TETRAS) and related tremor measurement approaches, alongside other clinical and neurophysiological measures described for neurological disorders.
Claims Coverage
The independent claim covers 2 inventive features centered on a specified crystalline anhydrous Form C hydrochloride of Formula (II) and an oral modified-release dosage form for treating essential tremor.
Xrpd-defined crystalline anhydrous form c hydrochloride of formula (ii)
An oral dosage form comprising a crystalline anhydrous Form C hydrochloride of Formula (II), wherein the crystalline anhydrous Form C hydrochloride of Formula (II) is characterized by an X-ray powder diffraction (XRPD) pattern comprising one or more of the peaks at diffraction angle 2θ: 26.6±0.2, 16.2±0.2, 17.4±0.2, 22.6±0.2, and 11.5±0.2.
Oral modified-release polymer for treatment of essential tremor
A method of treating an essential tremor in a patient in need thereof, comprising administering to the patient a sufficient amount of an oral dosage form comprising the crystalline anhydrous Form C hydrochloride of Formula (II) and a modified-release polymer.
The core inventive coverage is the combination of a specified crystalline anhydrous Form C hydrochloride of Formula (II) defined by an XRPD peak set and an oral modified-release dosage form including a modified-release polymer for treating essential tremor.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating an essential tremor in a patient in need thereof using an oral dosage form comprising crystalline anhydrous Form C hydrochloride of Formula (II) and a modified-release polymer.
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