CHICAGO – An off-the-market antihistamine previously shown to slow cognitive decline over 1 year in Alzheimer's patients continued to preserve cognition and memory during a 6-month open-label extension trial.
The drug, dimebon, also stabilized cognition in patients who started on it after taking placebo during the original trial, Dr. Jeffrey Cummings said at the International Conference on Alzheimer's Disease.
“People initially treated with placebo and then crossed over to dimebon did not show the same level of benefit as those people who took dimebon for 18 months after starting the [initial] study,” said Dr. Cummings, the Augustus S. Rose Professor of Neurology at the University of California, Los Angeles. “This emphasizes the benefit of earlier treatment, and suggests the possibility that dimebon may slow the progression of Alzheimer's.”
He pointed out, however, that the open-label extension trial can't provide definitive conclusions about any disease-modifying effects the drug might exert. “Open-label extensions are not the same as placebo-controlled trials, and extrapolation of the treatment results should be done with caution.”
The original trial enrolled 183 patients with mild to moderate Alzheimer's disease at 11 sites in Russia. Patients were randomized to placebo or dimebon 20 mg three times a day.
By the end of the study, those who took dimebon actually gained about 2 points on the Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog), while those taking placebo had declined almost 6 points from baseline.
Behavioral and psychiatric symptoms also were significantly improved in the active group, compared with the placebo group (Lancet 2008;372:207-15).
All 120 patients who completed the 12-month trial were offered the chance to continue for 6 more months in the open-label extension. Most (54 dimebon, 50 placebo) elected to enroll; of these 104, 92 (88%) completed the study.
Patients who completed a full 18 months of dimebon continued to show benefit on ADAS-cog and measures of behavioral and psychiatric symptoms. While there was a decline from the mean 12-month cognitive status, by 18 months cognition and memory were not significantly worse than they were at baseline. A similar pattern emerged in behavior and psychiatric symptoms.
Former placebo patients who crossed over to dimebon showed a cessation of their placebo-related decline, with a mean ADAS-cog score that stabilized at the 12-month crossover level.
The drug was well tolerated in both studies. Adverse events that were significantly more common among dimebon patients included dry mouth and depressed mood.
The drug's method of action is not fully understood, Dr. Cummings said. Dimebon had been used in Russia as a general antihistamine, but was withdrawn from the market when selective agents became available. Researchers discovered some potentially neuroprotective effects in the late 1990s; the drug may also have benefit in Huntington's disease.
Studies suggest that dimebon improves impaired mitochondrial function, which may prevent neuronal death and increase synaptic number and signalling, Dr. Cummings said at the meeting, which was sponsored by the Alzheimer's Association.
Dr. Cummings disclosed that he is a consultant for Medivation Inc., the San Francisco-based company that provided the dimebon for the study.