Submitted by Armen Hareyan on Sep 11th, 2007
Cognitive Impairment Associated With Schizophrenia
TorreyPines Therapeutics completed its third Phase I clinical trial for NGX267, in clinical development for the treatment of cognitive impairment associated with schizophrenia (CIAS).
The compound, a functionally selective muscarinic (M1) agonist, was found to be safe and well-tolerated when given orally to healthy male volunteers once-daily for four consecutive days. In two previous Phase I trials, NGX267, administered as single oral doses, was shown to be well-tolerated in healthy young adult males, as well as in healthy elderly males and females.
The purpose of the Phase I trial was to investigate the safety, tolerability and pharmacokinetics of multiple doses of NGX267 and to confirm data from previous studies in which NGX267 demonstrated evidence of muscarinic receptor stimulation as measured by increases in salivary flow.
A total of 60 healthy males, between the ages of 18 and 55, were enrolled in the double-blind, placebo-controlled trial conducted at one center in Belgium. In a series of sequential dosing cohorts, subjects received a single oral dose of either 10, 20, 30 or 35 mg of NGX267 once-daily for four consecutive days. NGX267 was well tolerated at doses up to and including 30 mg, a dose range believed to be effective for treating memory and cognitive disturbances.
TorreyPines plans to initiate a Phase II dose-ranging trial in CIAS during the first half of 2008. A secondary objective was to obtain quantitative measures of salivary flow, prior to and at multiple time points post-dosing, as a peripheral biomarker for stimulation of the muscarinic receptor. In the study, increases in peak and total salivary flow were detected for NGX267 in comparison to placebo.
These effects increased linearly with dose, were maintained over four days of dosing, and within subject peak increases in salivary flow correlated with peak plasma levels of NGX267. Decreased salivary flow results in dry mouth, or xerostomia, and is a symptom of a number of underlying conditions.
Causes of dry mouth include the autoimmune disorder Sjogren's Syndrome, radiation treatment to the head and neck, and HIV-related salivary gland disease. Xerostomia can also be a side effect of some medications and may be associated with aging.
"The data from this study are promising, given the low incidence of adverse events at potentially therapeutic doses for treating CIAS," said Neil Kurtz, M.D., President and Chief Executive Officer of TorreyPines. "In addition, the data not only confirm earlier findings that NGX267 increases salivary flow, but also demonstrates that the effect is seen at multiple dose levels and maintained after repetitive dosing. Moving forward, we now have data that suggests that this well-tolerated product candidate could be effective in treating not only CIAS, but also xerostomia. In addition to our planned Phase II study in CIAS, we will consider initiating a small proof of concept study for xerostomia early next year."
Source:
TorreyPines Therapeutics, Inc. 