Early Parkinson's Treatment With Rasagiline Safe, Well Tolerated, and Effective Versus Placebo

Early Parkinson's Treatment With Rasagiline Safe, Well Tolerated, and Effective Versus Placebo: Presented at ADPD

By Chris Berrie

PRAGUE, Czech Republic -- March 14, 2009 -- Rasagiline monotherapy is safe and well tolerated, with clinical benefits versus placebo in patients with early, previously untreated Parkinson's disease (PD), researchers noted here at the 9th International Conference on Alzheimer's and Parkinson's Diseases (ADPD).

Early initiation of treatment with rasagiline 1 mg/day also provided significant clinical benefits over later initiation.

A prospective, multicentre study entitled Attenuation of Disease Progression With Azilect Given Once-Daily (ADAGIO) was presented here on March 13 by principal investigator Olivier Rascol, MD, Toulouse University Hospital, Toulouse, France.

"A treatment that slows or halts the progression of disease is a key unmet need in Parkinson's disease," Dr. Rascol stated. He and his colleagues utilised a delayed-start design in their randomised, double-blind, placebo-controlled trial to allow separation of disease-modifying effects from symptomatic effects in the examination of patients with moderate to advanced PD taking rasagiline monotherapy and combination therapy with levodopa.

Patient diagnosis was for cardinal PD signs -- resting tremor, bradykinesia, and rigidity -- with inclusion requiring a disease duration of less than 18 months from diagnosis and investigator judgement of no requirement for additional anti-PD treatment in the following 9 months.

The 1,176 patients enrolled were 61.1% male, with mean baseline characteristics as follows: age, 62.2 years; PD duration, 4.5 months; total Unified PD Rating Scale (UPDRS) score, 20.4; motor-UPDRS score, 14.2; and modified Hoehn and Yahr score, 1.5.

The study followed 2 phases: a 36-week placebo-controlled phase 1, followed by a 36-week full active-treatment phase 2. Randomisation was to 4 groups -- 2 of placebo followed by rasagiline 1 or 2 mg/day for delayed-start treatment (n = 595) and 2 of rasagiline 1 mg/day (n = 288) or 2 mg/day (n = 293) for the full 72 weeks. There were no significant baseline differences across these groups.

With rasagiline 1 mg/day, the 3 specific primary efficacy endpoints were met:
A. The slope in weeks 12-36 of phase 1 was significantly superior with active treatment versus placebo (difference, -0.05; 95% confidence interval [CI], -0.08 to -0.01; P = .0133).
B. Results from the early-start group were significantly superior to those of the late-start group at week 72 (difference, -1.7; 95% CI, -3.15 to -0.21; P = .025).
C. The noninferiority of the slope of early versus late start was met (difference, 0.0; 90% CI, -0.04 to 0.04; P < .0001).

The rasagiline 2-mg/day treatment showed significant benefit in phase 1 versus placebo (P < .001), but did not show superiority versus the delayed start at the end of phase 2.

The secondary endpoint for changes in total UPDRS score from baseline to week 36 for each rasagiline group was met for rasagiline 1 and 2 mg/day, as adjusted effect sizes of -3.0 (95% CI, -3.9 to -2.2; P < .0001) and -3.2 (95% CI, -4.0 to -2.3; P < .0001) respectively.

Rasagiline monotherapy was deemed safe and well tolerated, with few treatment-related adverse events and few discontinuations (placebo, 2.9%; rasagiline 1 mg/day, 3.1%; rasagiline 2 mg/day, 3.8%).

The researchers concluded that this early treatment with rasagiline 1 mg/day is consistent with disease-modifying effects, noting, "ADAGIO also confirms the symptomatic efficacy of rasagiline monotherapy versus placebo in patients with early [Parkinson's] disease."

Funding for this study was provided by Teva Pharmaceutical Industries Ltd. and Teva Neuroscience, Inc.

[Presentation title: The ADAGIO Delayed-Start Study Demonstrates That Early Rasagiline Treatment Slows UPDRS Decline. Abstract P1-423]