A Phase II follow-on study with selective amyloid beta-42 lowering agent R-flurbiprofen indicates benefits are maintained through at least 21 months in patients with mild-to-moderate Alzheimer disease, according to a presentation at the annual meeting of the American Association of Geriatric Psychiatry.

In the first, 12-month-long, part of the study, 207 patients with mild Alzheimer disease in the UK and Canada were randomized to 400 or 800 mg drug daily or to placebo. After lower-than-expected drop-out, Canadian patients were given the option to continue in a 9-month follow-on study: 81 percent of participants enrolled. Patients who had received placebo were randomized into the 400 or 800 mg BID groups and were not included in the data presented for the follow-on study. Participants in either drug arm in the initial trial continued with the same dose

The 21-month data suggest that study participants on the higher dose of R-flurbiprofen demonstrated increasing benefit through month 21 in cognition and memory loss and maintained more of their abilities for global function and activities of daily living than people in the lower-dose or placebo groups.

Results of the Phase 2 study and a summary of 9-month follow-on data were presented by Daniel Christensen, MD, Clinical Professor of Psychiatry, Clinical Professor of Neurology and Adjunct Professor of Pharmacology at the University Neuropsychiatric Institute, Salt Lake City, Utah.

Efficacy in the first 12 months was measured as the difference between the rates of decline, or slopes, of the treated groups and the placebo group. In the follow-on study, because the placebo group has been randomized into the treatment arms, investigators measured the difference between the slopes of the treated groups and the slope of the placebo group during the first 12 months as extended through 21 months.

As measured by performance of activities of daily living (ADCS-ADL), higher-dose drug had a significant 52-percent effect size compared with projected placebo slope at 21 months. In terms of global function at 21 months, the CDR-sb scale showed a highly significant 75-percent effect size.

These data suggest there is a substantial benefit on activities of daily living and global function and that the benefit increases over time. Effect on cognitive decline as measured on the ADAS-cog scale also increased, with an effect size of 60 percent at 21 months.

Based on positive Phase II results, patients with mild Alzheimer disease are being enrolled in the USA for a Phase III trial. Patients will be randomized into one of two arms, receiving either 800 mg drug or placebo twice daily for the duration of the 12-month trial period. The study is designed to determine R-flurbiprofen’s ability to reduce the rate of cognitive decline and activities of daily living in patients with mild Alzheimer's disease, as measured by the ADAS-cog test and the change in ADCS-ADL, respectively.