Cognition Pharmaceuticals Announces Positive Memory Results for Phase II Trial of C105 in Multiple Sclerosis
Last update: 2:37 p.m. EST Dec. 17, 2008
NEW YORK, Dec 17, 2008 /PRNewswire via COMTEX/ -- Cognition
Pharmaceuticals LLC today announced positive results from a Phase 2 clinical trial of C105 (l amphetamine sulfate) on 151 Multiple Sclerosis patients with documented cognitive dysfunction
In the six-week placebo-controlled study, Cognition Pharmaceuticals reported, the active group obtained significantly higher scores on secondary outcome measures of memory and learning, including the Brief Visuospatial Memory Test - Revised, Total Recall (p = 0.041) and Delayed Recall (p < 0.01), and the California Verbal Learning Test, Long Delay Free Recall (p = .012). Safety data were unremarkable with a limited side-effect profile.
The company said that C105 demonstrated efficacy in improving memory function in patients with cognitive impairment secondary to MS. At the 30mg peak dose, the active group exhibited statistically significant improvement in performance on measures of both verbal and nonverbal delayed recall as well as improved memory retention.
A report of the study findings has been awarded a Merit designation by the International Neuropsychological Society ( www.the-ins.org
) in anticipation of its 2009 conference in Atlanta where the study will be presented. The International Neuropsychological Society is a multi-disciplinary non-profit organization dedicated to enhancing communication among the scientific disciplines which contribute to the understanding of brain-behavior relationships. The Merit designation means that the abstract was identified as being among the most highly rated of all research submitted and reviewed for the meeting.
While the results did not reach statistical significance for either of the two primary outcome measures focusing on processing speed and executive function (the Symbol Digit Modalities Test and the Subject's Global Assessment), the significant memory findings coupled with an encouraging safety profile clearly define the drug's effects and differentiate it from d-amphetamine in clinically meaningful ways, Cognition Pharmaceuticals said. Continued analyses of study data in several domains is in process.
"We are extremely encouraged by very strong findings in the areas of verbal and visual memory and learning from our trial. These memory results are consistent with and fit well with our understanding of the mechanism of action of C105 as documented in a range of preclinical and clinical studies," according to Cognition Pharmaceuticals President and Chief Scientific Officer David Erlanger, Ph.D.
The potential for C105 to help human memory was first identified by a team of researchers led by Mark Bear, Ph.D., currently Director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology. "In animals, we discovered that C105 can modulate memory consolidation -- a biochemical process by which temporary or labile changes in synaptic function are made enduring. We believe that C105 augments the function of modulatory systems in the brain that normally control memory strength. It is very exciting to see that this insight may be of therapeutic significance in humans with memory disorders."
Analyses of the full dataset from the trial are ongoing, with Drs. Ralph Benedict and Frederick Munschauer of the Jacobs Neurological Institute in Buffalo, New York serving as Co-Principal Investigators. A series of discussions with leading medical experts and publication of more detailed results over the coming months are under way.
About the Study
The Phase 2 trial was conducted by Cognition Pharmaceuticals, which described it as a randomized, double-blind, placebo-controlled, dose-titration study. A total of 151 subjects from 33 sites in the United States were randomized into the six-week trial at a ratio of 2:1, active to placebo. The population was composed of patients with a clinically definitive diagnosis of Multiple Sclerosis with evidence of cognitive impairment at intake. Inclusion criteria mandated that all enrolled patients demonstrate a pattern of impairment on the Symbol Digit Modalities test (a measure of processing speed), the California Verbal Learning Test (a measure of verbal learning and memory) and the Paced Auditory Serial Addition Test (a measure of working memory). Patients were screened for depression at intake, and those with evidence of an untreated Major Depressive Disorder were excluded. Dose was titrated over 14 days, and patients remained on a therapeutic dose for another 14 days. Patients were administered a standardized cognitive assessment battery (MACFIMS; Minimal Assessment of Cognitive Function in Multiple Sclerosis) at screening and stable peak dose, and a subset of this battery was administered on intervening study days and at a follow up visit.
The company said it was ready to initiate a pivotal study that establishes the endpoints for Phase III MS trials. Appropriate measures have been validated for use in the U.S. and Europe. It is anticipated that C105 can be submitted for NDA in early 2011 in this most direct path to approval. Additional plans for approval in other, larger markets, including Learning Disorders and Mild Cognitive Impairment, have also been developed.
About L-amphetamine sulfate
The levo enantiomer of amphetamine sulfate (l-amphetamine) is similar to dextro enantiomer (d-amphetamine), a widely used central nervous system (CNS) stimulant (known commercially as Dexedrine). Both C105 and d-amphetamine have similar activating properties for norepinephrine; however, C105 has a significantly smaller effect on dopamine resulting in a potent CNS stimulant with fewer unwanted side effects, including lower abuse potential. In multiple Phase I and II trials completed to date, C105 has demonstrated positive efficacy data and a favorable safety profile.