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Use of riluzole oral disintigrating tablets for treating diseases

A technology for riluzole and diseases, applied in muscular system diseases, nervous system diseases, neuromuscular system diseases, etc., can solve problems such as complex ability, low solubility, and dysphagia

Pending Publication Date: 2021-01-08
BIOHAVEN PHARMA HLDG CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The drug substance of riluzole itself has other inherent limitations that complicate the ability to produce non-tablet formulations (including very low solubility in water), poor oral palatability, pH-dependent chemical stability, and if administered directly Strong oral numbness in the oral mucosa
For example, an early symptom of many ALS patients is dysphagia, which makes swallowing traditional riluzole tablets particularly challenging for ALS patients

Method used

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  • Use of riluzole oral disintigrating tablets for treating diseases
  • Use of riluzole oral disintigrating tablets for treating diseases
  • Use of riluzole oral disintigrating tablets for treating diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0099] A phase 1 study to evaluate the bioequivalence between BHV-0223 (riluzole 40mg sublingual orally disintegrating tablet) and RILUTEK 50mg tablet and to evaluate the food effect of BHV-0223 in normal healthy volunteers

[0100] This study is sometimes referred to herein as BHV223-102. The main elements of the protocol used in the study are as follows.

[0101] Target

[0102] main target

[0103] Comparing the rate and extent of absorption of BHV-0223 administered sublingually at 1 x 40 mg ODT in NHV with RILUTEK administered orally as 1 x 50 mg tablet under fasted conditions.

[0104] • To evaluate the effect of food on the pharmacokinetics of BHV-0223 when given as a single 40 mg sublingual dose in NHV.

[0105] secondary goal

[0106] · To evaluate the safety and tolerability of BHV-0223.

[0107] • To assess the rate of sublingual absorption of crushed riluzole tablets (50 mg RILUTEK) in a subset of NHVs.

[0108] explore target

[0109] To explore the sy...

Embodiment 2

[0212] The research result of embodiment 1

[0213] The study (BHV223-102) was performed substantially as described in the protocol set forth in Example 1. The results are summarized below.

[0214] Results: In Part I, BHV-0223 achieved approximately 90% and 113% area under the curve (AUC) and maximum concentration exposure compared to RILUTEK, respectively. The 90% confidence interval is within the range of 80%-125% that FDA requires for bioequivalence. BHV-0223 produced AUC levels with a fed to fasted ratio of 92%. Crushed sublingual RILUTEK delivery had a 6% rate AUC level compared to oral RILUTEK.

[0215]SUMMARY / CONCLUSION: BHV-0223 is bioequivalent to RILUTEK 50mg oral tablet and therefore offers similar efficacy; but also potentially improves usability and reduces patient burden (no swallowing required, no need for fasting based on AUC) negative food effects); improved safety / tolerability (reduced risk of dose-related hepatic dysfunction); and enhanced pharmacology ...

Embodiment 3

[0334] Simulation and Modeling

[0335] Part A

[0336] use Modeling software to evaluate BHV-0223 40MG Effect of Sublingual Formulation and Riluzole 50MG Oral Tablet on Liver Function Test Parameters

[0337] The main elements of the simulation are summarized below.

[0338] Target

[0339] To quantitatively and mechanistically compare the hepatotoxicity potential of oral riluzole to BHV-0223 using DILIsym, combining clinical and mechanistic data. DILIsym is a registered trademark of Dilisym Services Inc., Durham, NC, USA.

[0340] method

[0341] Oral administration of riluzole (50 mg twice daily [BID] for 12 weeks) and sublingual riluzole (40mg BID for 12 weeks).

[0342] • The DILIsym PBPK model framework for Riluzole is composed of a compartment model of the human body with compartments for blood, intestine, liver, muscle and other tissues.

[0343] The PBPK representation of riluzole is based on available data from BHV-0223 and published riluzole studies...

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Abstract

Disclosed are methods of treating a disease in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of riluzole, or a pharmaceutically acceptable salt thereof, in the form of an oral solid molded fast-dispersing dosage form. Pharmaceutical compositions and kits are also disclosed.

Description

technical field [0001] The invention relates to the use of riluzole orally disintegrating tablet and its application in disease treatment. Background technique [0002] Glutamate is the major excitatory neurotransmitter responsible for regulating signaling in normal brain function. While studies of glutamate signaling have primarily focused on the central nervous system (CNS), other studies have highlighted their functional roles in peripheral tissues. See, eg, Skerry T, Genever P, Glutamate signaling in non-neuronal tissues. Trends Pharmacol Sci 2001, 22:174-181 and Frati C, Marchese C, Fisichella G, Copani A, Nasca MR, Storto M, Nicoletti F, Expression of functional Glu5 metabotropic glutamate receptors in human melanocytes. J Cell Physiol 2000, 183: 364-372. [0003] Glutamate can exert its signaling ability by acting on glutamate receptors located on the cell surface. Glutamate receptors exist as ionotropic receptors (iGluRs) or metabotropic glutamate receptors (mGluR...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/20A61K47/26A61K31/428
CPCA61K31/428A61K9/0056A61P25/28A61K9/2063A61K9/2095A61K9/006A61K9/2018A61P21/00
Inventor V·科里克R·伯曼I·库雷希
Owner BIOHAVEN PHARMA HLDG CO LTD
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