Lornoxicam and Alzheimer's Disease
A 6-month double-blind Phase II clinical multicenter trial (clinicaltrials.gov identifier: NCT01117948) with a 6-month open-label extension phase has been conducted in 219 patients with mild to moderate possible Alzheimer's disease. The study was prematurely terminated in 2011, solely because financing was withdrawn.
No statistically significant cognitive benefit was seen at the 6-month and 12-month endpoints. From today's perspective this is not surprising, given what the ADAPT extension has taught us and given that the participants in this trial had already been diagnosed with Alzheimer's disease.
It is now evident that this trial should have (1) been conducted in individuals who matched the new definition of "Mild Cognitive Impairment Due To Alzheimer's Disease" according to the 2011 National Institute of Aging-Alzheimer's Association criteria, and (2) that it should have lasted not one year but at least three years.
Lornoxicam: A New Investigational Proposal
Based on these insights a new clinical study has been designed with a bipartite, randomized, double-blind, placebo-controlled parallel-group design to evaluate the safety and efficacy of lornoxicam in individuals with MCI due to Alzheimer's disease according to current guidelines. The protocol has been structured in such a way that the initial phase could be conducted alone, serving as a pilot study.
A 12-month primary phase will be followed by a 24-month extension phase. The primary outcome parameter for the first phase will be the percentage of subjects progressing to clinical-stage Alzheimer's disease. Subjects who have no substantial cognitive decline and/or show no evidence of hippocampal volume loss, or who have biomarker improvements, are eligible to enter the 2-year double-blind extension phase. The final 3-year endpoint is the percentage of subjects progressing to clinical-stage Alzheimer's disease.
Advanced drug delivery technology will be employed to create a new oral presentation of lornoxicam that is specifically tuned to brain delivery, and might allow an adaptation of the dose. This formulation will have very little in common with lornoxicam tablets that are currently marketed as analgesics.
Therapeutic applications of lornoxicam in Alzheimer's disease are covered by international patent application WO 2004/105766 (priority date: May 27, 2003) which has matured into a granted European patent (EP 1 626 726 B1) and granted national patents in the United States (US 8,129,370 B2), Canada (CA 2 526 816 C), the Russian Fderation (RU 2 366 425 C2), and Korea (KR 10-1134244 B1).
Also see an overview of the entire patent familiy.