Compositions for the treatment of CNS-related conditions
Inventors
Went, Gregory T. • Fultz, Timothy J. • Meyerson, Laurence R.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8580858-B2
Publication Date
2013-11-12
Expiration Date
Abstract
The invention provides compositions comprising extended release memantine in combination with immediate release donepezil to a subject. Memantine in an extended release form containing 22.5 to 30 mg memantine or a pharmaceutically acceptable salt thereof in combination with donepezil achieves particular pharmacokinetic criteria such as change in plasma concentration of memantine over time and ratio of maximum memantine plasma concentration to mean memantine plasma concentration.
Core Innovation
The invention relates to methods of treating a patient with a neurological condition by orally administering an extended release dosage form of memantine to a human subject. The extended release memantine dose is provided as 22.5 to 37.5 mg memantine or a pharmaceutically acceptable salt thereof, and the administration of a dose provides a mean plasma memantine concentration profile characterized by a change in memantine concentration as a function of time (dC/dT) that is less than about 50% of the dC/dT provided by the same quantity of an immediate release form of memantine, determined in a time period between 0 hours to 6 hours of administration of memantine, and where dC/dT is measured in a single-dose human PK study.
In combination with the extended release memantine, the method further provides a therapeutically effective amount of immediate release donepezil. The neurological condition is selected from Alzheimer's disease, dementia, Parkinson's disease, and neuropathic pain.
The invention additionally emphasizes matching and optimization of pharmacokinetic release profiles, including altered Tmax and reduced dC/dT relative to immediate release, and reduced Cmax/Cmean and Cratio variability. Formulation strategies are described for oral dosage forms that include immediate release or extended release components, including pellets/beads in capsules and matched dissolution profiles.
Claims Coverage
The independent claim covers an oral treatment method that combines extended release memantine with immediate release donepezil. The claim includes three inventive aspects: a specific extended release memantine dose range, a pharmacokinetic dC/dT criterion assessed in a defined single-dose human PK study window with respect to immediate release memantine, and selection of the neurological condition from a specified set of disorders.
Extended release memantine with reduced dC/dT vs immediate release
Orally administering 22.5 to 37.5 mg memantine or a pharmaceutically acceptable salt thereof in an extended release dosage form, wherein administration provides a mean plasma memantine concentration profile characterized by a dC/dT that is less than about 50% of the dC/dT provided by the same quantity of an immediate release form of memantine, with dC/dT measured in a single-dose human PK study over a time period between 0 hours to 6 hours.
Immediate release donepezil co-administered at therapeutically effective amount
Administering a therapeutically effective amount of immediate release donepezil in combination with the extended release memantine method.
Neurological condition selected from defined disorder set
Treating a neurological condition selected from Alzheimer's disease, dementia, Parkinson's disease, and neuropathic pain using the oral administration of the extended release memantine and the therapeutically effective amount of immediate release donepezil.
The inventive coverage centers on orally treating selected neurological conditions using extended release memantine that satisfies quantitative dC/dT criteria versus immediate release in a single-dose human PK study, together with immediate release donepezil at a therapeutically effective amount.
Stated Advantages
Avoid dose escalation.
Reduce adverse effects.
Documented Applications
Treatment of a patient with neurological conditions selected from Alzheimer's disease, dementia, Parkinson's disease, and neuropathic pain using oral administration of extended release memantine together with immediate release donepezil.
Example safety/PK and efficacy study designs assessing Alzheimer’s patients.
Interested in licensing this patent?