Source: DGNews  |  Posted 2 years ago

By Ed Susman

VIENNA, Austria -- July 14, 2009 -- Rosiglitazone shows no significant benefit in patients with mild to moderate Alzheimer's disease, according to an analysis of the secondary endpoints of a clinical trial presented here at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease (ICAD).

"The main trial was also negative," said Claire Alderton, Neurological Studies, Neurosciences Medicines Development Center, GlaxoSmithKline, Greenford, Middlesex, United Kingdom, on July 12. "These results were very disappointing."

The secondary endpoints of the study attempted to show that treatment with rosiglitazone would have an impact on patients who were stratified by their genetics, specifically if the patients did not have the apolipoprotein E4 (APOE4) gene.

Alderton said the study was an outgrowth of a previous clinical trial that saw some improvement in this population as opposed to other groups of patients.

"The study did not detect significant efficacy for rosiglitazone extended release 2 mg or 8 mg or donepezil on measures of behaviour or activities of daily living after 6 months of treatment," she said.

"Responder rates based on improvement in cognitive function were highest for the rosiglitazone extended release 2 mg, suggesting that dose was associated with better response in a subpopulation of subjects. Responder rates for donepezil were lower than in registration clinical trials for donepezil."

Researchers enrolled 581 patients (~72 years; 62% female) into the 24-week, double-blind, randomised, parallel-group study with a 4-week placebo run-in and a 2-week follow-up. They assigned 166 patients to placebo; 166 to rosiglitazone extended release 2 mg; 165 to rosiglitazone extended release 8 mg; and 84 patients to donepezil. They had been experiencing symptoms of cognitive decline for about 4 years.

There were no significant differences observed in any patient group after 24 weeks in the Disability Assessment for Dementia score nor were there any significant differences observed in any treatment group at week 24 for the Neuropsychiatric Inventory score.

Caregiver hours for basic activities were significantly reduced among patients receiving rosiglitazone extended-release 2-mg dose for patients who were APOE4-negative (P = .05), for all patients except those who were 2 E4 mutations (P = .01), and for the full population (P = .03). Donepezil reduced caretaker hours for basic activities (P = .03). There were no groups in which caretaker hours for instrumental activities were reduced.

Funding for this study was provided by GlaxoSmithKline.

[Presentation title: Secondary Endpoint and Responder Analyses in a Study of Rosiglitazone XR in APOE4-Stratified Subjects With Mild-to-Moderate Alzheimer's Disease. Abstract P1-263]