Following one of the largest studies ever conducted in Parkinson’s disease (PD), researchers at Mount Sinai School of Medicine report today in The New England Journal of Medicine that rasagiline, a drug currently used to treat the symptoms of PD, may also slow the rate of disease progression.
Known as ADAGIO (Attenuation of Disease Progression with Azilect Given Once Daily), the 18-month study used a novel design called the delayed start. In this type of study, patients are randomized to start active treatment early or late, and then researchers look to see if early treatment influences the outcome at final visit when patients in both groups are on the same treatment.
ADAGIO showed that previously untreated PD patients randomized to initiate therapy with rasagiline (Azilect(R)) 1 mg per day had benefits at 18 months that were not achieved when the same drug was initiated at nine months. These results are consistent with the possibility that the drug has a disease-modifying effect which slows disease progression. The study examined both 1- and 2-mg doses of rasagiline using a rigorous design that included three primary endpoints. The 1-mg dose met all three primary endpoints. The 2-mg dose did not.
C. Warren Olanow, MD, Henry P. and Georgette Goldschmidt Professor and Chairman Emeritus, Department of Neurology, Mount Sinai School of Medicine, was the principal investigator of the trial.
The first PD trial to use delayed start as its primary design, ADAGIO was one of the largest trials ever conducted in this disease and included 1,176 patients with very early PD in 14 countries and 129 medical centers. They were randomized to receive rasagiline 1 or 2 mg per day for 72 weeks (early start) or placebo for 36 weeks followed by rasagiline 1 or 2 mg per day for 36 weeks (delayed start).
PD is a degenerative neurological condition that affects more than a million Americans. Early stages of the disorder are associated with impaired motor skills including tremor, stiffness, and slowness of movement. As the disease progresses, impairments become more severe and can include gait disturbance with falling and dementia.
The three primary endpoints used in this study were based on the Unified Parkinson’s Disease Rating Scale (UPDRS), which is used to track PD progression in areas such as mental state, activities of daily life, and motor skills. The three endpoints were: 1) the rate of UPDRS deterioration between weeks 12 and 36 in the early start vs. placebo groups; 2) the change in UPDRS score between baseline and final visit (week 72) in the early treatment group compared to the delayed treatment group; 3) and a demonstration of non-inferiority of the early treatment group vs. the delayed start group in the rate of worsening of UPDRS score between weeks 48 and 72 (i.e., whether the benefit was enduring).
Rasagiline is marketed as Azilect(R) in the United States by Teva Pharmaceuticals and was approved by the U.S. Food and Drug Administration in May 2006 for the treatment of the signs and symptoms of idiopathic PD as initial monotherapy and as adjunct therapy to levodopa.
Dr. Olanow has served as a consultant to Teva, which sponsored the ADAGIO study.
Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants. For more information, please visit www.mountsinai.org.