The agent called Neupro represents both the first transdermal patch for Parkinson's and the first U.S. approval of any kind for the active ingredient, the dopamine agonist rotigotine, the agency announced.
The silicone-based patch delivers a measured dose of rotigotine, a nonergoline agent, over 24 hours.
According to the FDA, the effectiveness of Neupro was demonstrated in a fixed-dose response study and two flexible-dose studies. The parallel group randomized, double-blinded, placebo-controlled studies involved 1,154 patients with early Parkinson's who were not on other anti-Parkinson's agents.
The most commonly reported adverse events in clinical trials included patch-site skin reactions, dizziness, nausea, vomiting, drowsiness and insomnia. Other adverse events included narcolepsy-like sleep attacks, hallucinations, and postural hypotension.
In an open-label extension study of the patch, reported at the American Neurological Association meeting last October, 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, said Ray L. Watts, M.D., chairman of neurology at the University of Alabama at Birmingham.
In an early online release from the Jan. 23 issue of Neurology, Dr. Watts and colleagues reported that early-stage Parkinson's responded with significant relief of symptoms, compared with placebo, for at least six months with rotigotine, with acceptable side effects.
In the Neurology 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.