BIRMINGHAM, Ala. -- Early-stage Parkinson's disease responded with significant relief of symptoms for at least six months with an investigational skin patch designed to deliver a steady dose of the dopamine agonist rotigotine, researchers here reported.
BIRMINGHAM, Ala., Jan. 4 -- Early-stage Parkinson's disease responded with significant relief of symptoms for at least six months with an investigational skin patch designed to deliver a steady dose of the dopamine agonist rotigotine, researchers here reported.
In a multicenter, randomized study, transdermal rotigiotine, a nonergoline agent, was superior to placebo at reducing the symptoms of Parkinson's disease, with acceptable side effects, reported Ray L. Watts, M.D., chairman of neurology at the University of Alabama at Birmingham, and colleagues.
"Transdermal rotigotine, when titrated to a dosage of 6 mg per 24 hours, was effective for the treatment of early-stage Parkinson disease in this trial," the authors wrote in an early online release from the Jan. 23 issue of Neurology. "Adverse events were similar to those found with other transdermal systems and dopamine agonists."
The clinically important valvular heart disease effects from dopamine agonists reported in the Jan. 4 issue of the New England Journal of Medicine involved ergot-derived agents, not non-ergot-derived dopamine agonists, such as rotigotine.
Dr. Watts reported results of an open-label extension study of the patch at the annual meeting of the American Neurological Association last October. In that report, the 137 patients on the active medication showed an immediate reduction in scores on the Unified Parkinson's Disease Rating Scale (UPDRS) of about seven points, and after six months that score remained four points below baseline.
At the end of the trial, the patients who had been on placebo and were then switched to the patch in the open-label extension phase showed an immediate drop in the Unified Parkinson's Disease Rating Scale scores, but as with the patients who continued on rotigotine, the scores slowly rose during the 85 week total length of the study.
In the current study, which reported the results of the original double-blind randomized study, patients were randomly assigned to placebo (96 patients) or rotigotine (181 patients).
Rotigotine was started at a dose of 2 mg/24 hours (10-cm2 patch size; 4.5-mg total drug content), titrated weekly up to 6 mg/24 hour (30-cm2 patch size; 13.5-mg total drug content), and then maintained for six months.
The primary efficacy measures were change from baseline in the UPDRS parts II and III scores, and percentage of responders, defined as patients with at least a 20% improvement.
The authors found that patients receiving rotigotine had a mean absolute difference of 5.28 (+ 1.18) points lower in UPDRS subtotal scores compared with those receiving placebo (P<0.0001).
The largest contributor to the difference was the mean change in UPDRS part III motor score, which decreased by 3.50 points (+ 7.26).
Nearly half of all patients who received rotigotine (48%) had at least a 20% improvement in UPDRS score, compared with about 19% of patients on placebo. (P<0.0001).
Adverse events included application-site reactions in 44% of patients on rotigotine versus 12% of those on placebo, nausea in 41% versus 17% respectively, somnolence in 33% of those on active drug versus 20% of those on placebo, and dizziness in 19% of those on rotigotine versus13% of controls
Most of the side effects were mild or moderate in intensity. In all, 14% of patients on the active drug and 6% of those on placebo discontinued using the patch because of adverse events.
"One limitation of the study design," the authors pointed out, "is that it is too short a time period to capture data related to the development of motor complications in early Parkinson's disease patients."
"However," they added, "a three-year open-label extension trial is ongoing to monitor the longevity of rotigotine treatment effects as well as patients' overall health and functioning. Over 95% of the patients who completed the double-blind maintenance period elected to continue into the open-label extension."