SAN FRANCISCO – The widely used anti-Alzheimer's disease drug galantamine also is effective in the treatment of patients with vascular dementia, Dr. Alexander P. Auchus said at the annual meeting of the American Academy of Neurology.
Galantamine proved significantly more effective than placebo at improving cognition and executive function in a phase III randomized clinical trial unique in that it was the first ever to employ expert MRI evaluators at a central radiology laboratory to confirm that participants indeed had vascular dementia, said Dr. Auchus of Case Western Reserve University, Cleveland.
There is at present no Food and Drug Administration-approved therapy for vascular dementia. Johnson & Johnson, sponsor of the phase III trial, doesn't intend to apply for a separate indication for galantamine in the treatment of vascular dementia, because only one of the study's two primary end points achieved statistical significance. But there is clear evidence of efficacy based upon multiple other study end points, and physicians will want to examine the data and decide for themselves whether this therapy is worth considering for their patients, the physician told this newspaper.
He reported on 788 patients diagnosed with vascular dementia by National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria with MRI confirmation who were randomized to galantamine or placebo in a double-blind 26-week trial conducted at 146 sites in 21 countries. Galantamine-treated patients received either 8 or 12 mg b.i.d. at the investigator's discretion.
One primary outcome measure was improvement in cognitive-related performance as assessed by the 11-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Galantamine-treated patients had significantly greater improvement in this domain, with a mean 1.8-point reduction at week 26, compared with a 0.3-point decrease in the placebo arm.
The other primary study end point–the one that didn't reach statistical significance–was improvement in a patient's ability to perform activities of daily living as assessed by the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL). Scores improved from baseline in both the galantamine and placebo groups. This was the deal-wrecker in terms of a new indication for the drug, according to Dr. Auchus.
But the galantamine-treated patients did experience significantly greater improvement in executive function, a secondary study end point, than did the placebo group. Galantamine-treated patients had a mean 2.4-point reduction in the 25-item Executive Interview (EXIT-25) score at week 26, compared with a 1.4-point decline in the placebo group.
The only side effects that were significantly more common in the galantamine group were insomnia and cholinergic GI symptoms.
