A crossover study compared Rytary with Stalevo, which is carbidopa and levodopa plus a COMT inhibitor (entacapone), a formulation intended to extend the usable life of the carbidopa–levodopa. Rytary reduced mean off time from 35% to 24%.
“This is pretty exciting because, unlike the levodopa gel, which is really going to fit into a niche of motor fluctuations in advanced patients, this [timed-release formulation] could potentially be used for patients with a new diagnosis,” Dr. Charles said.
DBS in Early Parkinson’s Disease
DBS was first approved in the United States in 1997 for essential tremor and unilateral tremor from Parkinson’s disease. The first implantation site was the ventral intermediate nucleus of the thalamus. In 2002, the indication was extended to implantation in the subthalamic nucleus and the globus pallidus interus. An indication for dystonia followed in 2003. The current indication for DBS is advanced Parkinson’s disease when symptoms are no longer adequately controlled.
The EARLYSTIM study, a large European trial that enrolled about 250 patients with mid-stage disease, was completed a few years ago. Participants in this open-label study had motor fluctuations and dyskinesias and had been on medicine for several years. The only blinded rating was the UPDRS part 3. The primary end point of the study was quality of life, which was 26% better with DBS than on pharmacologic treatment. All of the other measures were better in the DBS group as well. UPDRS part 4, which measures levodopa-associated dyskinesias, was 60% better in the DBS group and got 13% worse in the medicine group.
Dr. Charles and colleagues at Vanderbilt University recently completed a pilot trial of DBS of the subthalamic nucleus plus optimal drug therapy versus optimal drug therapy alone in 30 patients with very early-stage Parkinson’s disease. The results were encouraging, and Vanderbilt recently received FDA approval to conduct a multicenter, phase III, pivotal clinical trial in 280 patients with early stage Parkinson’s disease. Eligible patients can be on medication for no more than four years and can never have had a history of motor fluctuations or dyskinesias. “This trial will be evaluating DBS in a very early stage of Parkinson’s disease to determine if DBS is superior to medical therapy, reduces the relative risk of worsening, and suppresses the development of complications of medical therapy, such as motor fluctuations and dyskinesias,” Dr. Charles said.
—Glenn S. Williams
