Week of February 10 - February 16, 2008

Forest Laboratories, Inc. just announced preliminary results of a Phase III study of memantine HCl (currently marketed in the USA as Namenda in a twice-daily immediate-release formulation) in a novel once-daily formulation. The study evaluated the efficacy, safety, and tolerability of an innovative, proprietary, 28 mg memantine extended-release, once-daily formulation compared to placebo in outpatients with moderate to severe Alzheimer's disease currently treated with a cholinesterase inhibitor. The results indicate that patients treated with memantine 28 mg extended-release formulation experienced statistically significant benefits in cognition and clinical global status compared to placebo. Additional data from the study are expected to be presented later in the year.

The recommended dose for Namenda is currently 10 mg two times a day (20 mg/day), or for patients with severe renal impairment 5 mg twice a day (10 mg/day). Patients in this study were titrated to 28 mg/day in a once-daily modified release formulation. Namenda is currently available in tablets or liquid form.

"The higher dosage and once-daily formulation will provide patients with the efficacy and tolerability expected from Namenda, in a more convenient once-daily form," said Ivan Gergel, M.D., Senior Vice President of Scientific Affairs at Forest Laboratories and President of the Forest Research Institute. "Based on the results of this study, Forest plans to pursue a new drug application for the memantine extended-release once-daily formulation."

About the Study

A randomized, double-blind, placebo-controlled trial of 677 outpatients taking a cholinesterase inhibitor was conducted in multiple centers in Argentina, Chile, Mexico, and the U.S. Patients in the 24-week study were randomly assigned to receive either 28 mg/day of memantine extended release or placebo. The primary endpoints evaluated were change from baseline on the Severe Impairment Battery (SIB) and the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) rating at week 24. The study showed statistically significant higher cognitive abilities, as measured by the SIB, and clinical global status, as measured by the CIBIC-Plus, in patients treated with memantine 28 mg extended release compared to those treated with placebo (p=0.001 for SIB and p=0.008 for CIBIC-Plus, both using the pre-defined last observation carried forward analyses). The study also showed that the once-daily memantine extended-release formulation was well tolerated. The most common adverse events occurring at a higher rate than placebo were dizziness, diarrhea and headache.

Since this was a successful "Phase III" trial, it implies that FDA approval of the new formulation is near at hand, though no official timeline has been anounced. If you are taking Namenda, keep an eye out for the new formulation.

About Namenda

Namenda (memantine HCl) is the first in a class of medications with a unique mechanism of action that focuses on the glutamate pathway, a target for the treatment of Alzheimer's disease. Currently, all Alzheimer's disease medications approved in the U.S. other than Namenda belong to a class of agents called cholinesterase inhibitors.

Indicated for the treatment of moderate to severe Alzheimer's disease, the FDA approved Namenda in October 2003 based on three studies of Namenda used alone as monotherapy or in patients on a stable dose of donepezil (Aricept). Namenda is contraindicated in patients with known hypersensitivity to memantine HCl or any excipients used in the formulation.

The most common adverse events reported with Namenda (greater than or equal to 5% and higher than placebo) in placebo-controlled trials in patients with Alzheimer's disease were dizziness, confusion, headache, and constipation. In patients with severe renal impairment, dosage should be reduced.

About Forest Laboratories and Its Products

Sources:

Forest Laboratories Press Release

By:

Reviewed for medical accuracy by
Dr. B. Ancselovits, MD, Geriatrician, Alzheimer's Weekly

Edited by Peter Berger, Alzheimer's Weekly

Copyright:

Copyright © 2008 Alzheimer's Weekly. All rights reserved.