Intranasal delivery of levodopa power by precision olfactory device

A levodopa, powder technology, applied in the field of intranasal delivery of levodopa powder through a precision nasal device, can solve the problems of difficult patient management, high incidence, tolerance problems, etc.

Pending Publication Date: 2020-10-20
IMPEL NEUROPHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Sublingual apomorphine, also in development, has the ability to resolve OFF events, but may have tol

Method used

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  • Intranasal delivery of levodopa power by precision olfactory device
  • Intranasal delivery of levodopa power by precision olfactory device
  • Intranasal delivery of levodopa power by precision olfactory device

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0143] Example 1: Non-human primate PK studies

[0144] A series of L-DOPA (levodopa) powder formulations were developed and manufactured to evaluate the pharmacokinetics of intranasal administration of levodopa in non-human primates ("NHP"). The goal of powder formulation development was to achieve a formulation that would result in a rapid increase in plasma concentration to >200 ng / mL, preferably >400 ng / mL after intranasal delivery using a non-human primate precision nasal delivery ("nhpPOD") device, So that the preparation is expected to positively affect the "OFF" event in Parkinson's disease.

[0145] Four single-dose PK studies were performed in cynomolgus monkeys to examine PK following administration of a multipowder L-DOPA formulation delivered by the intranasal route using the nhpPOD device. Formulations examined included unmodified crystalline powder (median particle size ~50 μm), sieved formulations containing crystalline L-DOPA particles in a defined size range...

Embodiment 2

[0244] Example 2: Phase IIa, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Safety and Pharmacokinetics of INP103 (PODL-DOPA) Administered to Levodopa-Responsive Parkinson's Disease Patients in the Presence of Benserazide Kinetic / pharmacodynamic studies

[0245] Research design

[0246] A powder formulation of L-DOPA (levodopa) was tested in a randomized, double-blind, placebo-controlled, single ascending dose study to demonstrate precision nasal delivery via I231 Safety, tolerability and PK / pharmacodynamics of L-DOPA delivered by device to human subjects. The I231 POD device is a hand-held, manually actuated, propellant-driven, metered-dose administration device designed to deliver powder pharmaceutical formulations to the nasal cavity.

[0247] Intranasal administration was performed as single ascending doses of L-DOPA administered (aspirated) once (35 mg), twice (70 mg) or four times (140 mg) into the nostrils. L-DOPA was administered 60 minutes af...

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Abstract

Methods are provided for treating OFF episodes in a patient with Parkinson's disease or a Parkinson syndrome, comprising administering to a subject with Parkinson's disease or a Parkinson syndrome experiencing an OFF episode an effective dose of a dry pharmaceutical composition comprising L-DOPA, wherein the dose is administered by an intranasal delivery device that provides, following intranasaladministration, (a) a mean peak plasma levodopa concentration (Cmax) of at least 200 ng/mL, with (b) a mean time to Cmax (Tmax) of levodopa of less than or equal to 60 minutes. Dry pharmaceutical compositions of levodopa suitable for intranasal administration and unit dosage forms comprising the dry pharmaceutical compositions are also provided.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 62 / 700,591, filed July 19, 2018, and U.S. Provisional Application No. 62 / 614,310, filed January 5, 2018, the disclosures of which are incorporated by reference in their entirety This article. Background technique [0003] In patients with Parkinson's disease, OFF episodes occur when levodopa (L-DOPA) levels are subtherapeutic and may occur upon waking in the morning or sporadically throughout the day. A rapid reduction in OFF events will provide improved quality of life and activities of daily living by allowing more ON time. [0004] However, existing treatments for OFF events are insufficient. Although alternatives for OFF events are emerging, these new alternatives may be suboptimal for various subtypes of Parkinson's disease patients. For example, the FDA recently approved orally inhaled levodopa (INBRIJA) for the treatment of Parkinson's diseas...

Claims

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Application Information

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IPC IPC(8): A61P25/16A61K9/14A61K31/135
CPCA61P25/16A61K9/0043A61K9/0053A61K9/1623A61K9/1652A61K9/1611A61K31/198A61K31/165A61K2300/00A61M15/003A61M15/0036A61K31/197A61M15/009
Inventor J·D·赫克曼K·H·萨特利I·达舍夫斯基A·R·达斯S·B·什雷斯布里
Owner IMPEL NEUROPHARMA INC
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