• DOI:10.1056/NEJMoa0809335
• Corpus ID: 205090649

A double-blind, delayed-start trial of rasagiline in Parkinson's disease.

@article{Olanow2009ADD,
  title={A double-blind, delayed-start trial of rasagiline in Parkinson's disease.},
  author={C. Warren Olanow and Olivier Rascol and Robert A. Hauser and Paul D. Feigin and Joseph Jankovic and Anthony E. Lang and W. J. Langston and Eldad Melamed and Werner Poewe and Fabrizio Stocchi and Eduardo Tolosa},
  journal={The New England journal of medicine},
  year={2009},
  volume={361 13},
  pages={
          1268-78
        }
}

• C. Olanow, O. Rascol, +8 authors E. Tolosa
• Published 10 December 2009
• Medicine, Psychology
• The New England journal of medicine

BACKGROUND
A therapy that slows disease progression is the major unmet need in Parkinson's disease.

METHODS
In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72.

RESULTS
Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (+/-SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09+/-0.02 points per week in the early-start group vs. 0.14+/-0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82+/-0.53 points in the early-start group vs. 4.52+/-0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085+/-0.02 points per week in the early-start group vs. 0.085+/-0.02 points per week in the delayed-start group, P<0.001). All three end points were not met with rasagiline at a dose of 2 mg per day, since the change in the UPDRS score between baseline and week 72 was not significantly different in the two groups (3.47+/-0.50 points in the early-start group and 3.11+/-0.50 points in the delayed-start group, P=0.60).

CONCLUSIONS
Early treatment with rasagiline at a dose of 1 mg per day provided benefits that were consistent with a possible disease-modifying effect, but early treatment with rasagiline at a dose of 2 mg per day did not. Because the two doses were associated with different outcomes, the study results must be interpreted with caution. (ClinicalTrials.gov number, NCT00256204.)