Rotigotine

The Parkinson's-Reversing Breakthrough

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Rotigotine is a novel, nonergoline dopamine agonist, which is unique in that it is delivered through a silicone-based, skin patch system. It affects all of the dopamine receptors, with a 20-fold prevalence for D3 over D2 and 100-fold prevalence of D2 over D1 receptors. Rotigotine also exhibits antagonistic activity on alpha-2 receptors and agonistic activity on 5-HT1A receptors comparable to that of D2 and D1 receptors (49). Administration of this drug through a transdermal application can deliver a stable drug release and a steady-state plasma concentration over a 24-hour period, reduce peak dose or wearing-off adverse effects, and circumvent gastrointestinal metabolism (50). Side effects for rotigotine are similar to other dopamine agonists, but also include skin reactions from the patch.

Currently, this drug is approved in Europe and has received an approvable letter in the United States. In a multicenter, dose-ranging trial of rotigotine versus placebo, 242 subjects with early, untreated, idiopathic PD (average duration of PD 1.3 years) were assessed. For 11 weeks, subjects were randomly assigned to treatment with patches containing 4.5, 9.0, 13.5, or 18.0 mg of active or placebo monotherapy. The primary outcome was the change in the sum of the UPDRS ADL and motor scales between baseline and the 11-week visit. ADL scores were significantly improved relative to placebo in the 18.0 mg group only, whereas the motor score was improved in both the 13.5 and 18.0 mg groups. There was a dose-response relationship from 4.5 to 13.5 mg, with a plateau between 13.5 and 18.0 mg. The sum scores of UPDRS ADL and motor subscales showed significant improvement by week 4 in the 9.0, 13.5, and 18.0 mg groups and persisted throughout the maintenance phase (51).

In a second trial, 277 patients with early PD were enrolled in a double-blind, placebo-controlled, 27-week trial. Subjects were randomized to either rotigotine or placebo in a 2:1 ratio, and titrated weekly in 4.5 mg increments to an optimal response or maximum dose of 13.5 mg/d. The rotigotine group had a significant mean improvement of 4 points in UPDRS ADL and motor scores compared to a worsening of 1.3 points in the placebo group (P < 0.0001) (52).

Studies evaluating the efficacy of rotigotine in patients with advanced PD as an adjunctive therapy to levodopa have also demonstrated efficacy. One multicenter study of 351 subjects with advanced PD inadequately controlled with levodopa randomized subjects to rotigotine (18 or 27mg/d) or placebo in a 29-week study. Those who received rotigotine at 27 mg had a decrease in off time of 2.1 hours, the 18 mg group had a decrease of 2.7 hours, and the placebo group had a decrease of 0.9 hours. There was no increase in troublesome dyskinesia (53).

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