Results of ADAGIO trial for rasagiline suggest possible disease-modifying effect

The New England Journal of Medicine reports exciting results today regarding the ADAGIO trial for rasagiline (Azilect). A follow up to the previous TEMPO study (Arch Neurol 61:561-566, 2004), ADAGIO is one of the first true tests in Parkinson's disease of the ‘delayed start’ clinical trial design. Results suggest, not without caveats, that rasagiline may have a disease-modifying effect.

The trial randomized a whopping 1176 people with PD not yet receiving antiparkinsonian medication to receive either 1mg or 2mg rasagiline, or placebo control. An ‘early-start’ group was on active drug for the full 72-week duration of the trial, while a ‘delayed-start’ group was initially on placebo and then switched to active drug at week 36 for the remainder of the trial. Rasagiline at either 1mg or 2mg doses had to meet three pre-specified trial efficacy endpoints (a combination of slope and difference measures) to be considered ‘disease modifying’.

The authors report that 1mg rasagiline successfully acheived all three study endpoints, but 2mg rasagiline met only two of the three endpoints. A post-hoc analysis of subjects in the highest quartile of baseline UPDRS scores indicated that both doses met all three endpoints. The authors theorize that perhaps the milder subjects at baseline benefited so much symptomatically from 2mg rasagiline that it masked any possible disease-modifying effect, which could only therefore be teased out by looking at the slightly more severe subjects. Despite the intriguing hypothesis, the difference in findings between the two doses in the primary analysis led the study authors to conclude that a definitive demonstration of rasagline's disease-modifying ability could not yet be shown.

C. Warren Olanow, M.D., Olivier Rascol, M.D., Ph.D., Robert Hauser, M.D., Paul D. Feigin, Ph.D., Joseph Jankovic, M.D., Anthony Lang, M.D., William Langston, M.D., Eldad Melamed, M.D., Werner Poewe, M.D., Fabrizio Stocchi, M.D., and Eduardo Tolosa, M.D., for the ADAGIO Study Investigators. A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease. N Engl J Med 2009;361:1268-78.