Neupro (rotigotine)

Neupro is a transdermal delivery system that provides rotigotine, a non-ergolinic dopamine agonist, continuously over a 24-hour period. The exact mechanism of action of rotigotine in the treatment of Parkinson's disease is unknown.

Neupro is specifically indicated for the the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease.

Neupro is supplied as a patch in 2, 4, and 6 mg strengths designed for transdermal administration. The recommended initial dose of the drug is 2 mg/24 hours. Based on individual response and tolerability, the dosage may be increased weekly by 2 mg/24 hours if tolerated and additional therapeutic effect is needed. The lowest effective dose was found to be 4 mg/24 hours. The highest recommended dose is 6 mg/24 hours. The discontinuation of Neupro should be done gradually. The daily dose should be reduced by 2 mg/24 hours with a dose reduction preferably every other day, until complete withdrawal.

FDA Approval
FDA approval of Neupro was based on the results of three clinical studies. These parallel group, randomized, double-blind, placebo controlled studies enrolled subjects internationally. All subjects were not receiving concomitant dopamine agonist therapy and were either L-dopa naïve or off L-dopa for at least 28 days prior to baseline and were never on L-dopa for more than 6 months. The primary endpoint was the change from baseline for the combined scores for Part II (activities of daily living component) plus part III (motor component) of the Unified Parkinson’s Disease Rating Scale (UPDRS).

Dose Response Study
This randomized, double-blind, dose-response trial enrolled 316 early stage Parkinson's subjects. Subjects received either placebo or one of several fixed doses (2 mg/24 hours, 4 mg/24 hours, 6 mg/24 hours, or 8 mg/24 hours) of Neupro, given as 1, 2, 3, or 4 2-mg patches for a period up to 11 weeks. Subjects underwent a weekly titration over four weeks. They then continued on treatment for a 7 week maintenance phase followed by a down titration during the last week. Mean baseline combined UPDRS scores were similar among all treatment groups, between 27.1 and 28.5. Subjects experienced a mean improvement in the combined UPDRS from baseline to end of treatment of -3.5, -4.5, -6.3, and -6.3 for the 2 mg/24 hours, 4 mg/24 hours, 6 mg/24 hours, and 8 mg/24 hours Neupro groups respectively and -1.4 for the placebo group. Statistical significance was observed at the three highest doses.

North American Study
This randomized, double-blind trial enrolled 277 early stage, idiopathic Parkinson's Disease subjects who were randomized in a 2:1 ratio to receive Neupro (2, 4, or 6 mg/24 hours) or placebo for 28 weeks. Subjects underwent a weekly titration over 3 weeks to a maximal dose of 6 mg/24 hours depending on efficacy and tolerability, and then received treatment over a 24 week maintenance phase followed by a de-escalation over a period up to 4 days. Mean baseline combined UPDRS was similar in both groups, 29.9 for the Neupro group and 30.0 for placebo. Statistical significance was reached in the Neupro treated subjects versus placebo in the mean change in the combined UPDRS from baseline to end of treatment ( -4.0 versus +1.39, respectively).

Foreign Multinational Study
This randomized, double-blind trial, three arm, parallel group, double-dummy trial enrolled 561 subjects with early stage Parkinson's Disease. Subjects were assigned to treatment with either placebo, Neupro (2 mg/24 hours, 218 4 mg/2 hours, 6 mg/24 hours, or 8 mg/24 hours) or active oral comparator in a ratio of 1: 2: 2 for a period of up to 39 weeks. Subjects underwent a weekly dose escalation of patch (consisting of 2 mg/24 hours increments of Neupro or placebo) and a dose escalation of capsules of comparator or placebo over 13 weeks up to a maximal dose of 8 mg/24 hours of Neupro. Subjects randomized to Neupro achieved the maximal dose of 230 mg/24 hours after a 4 week titration if maximal efficacy and intolerability had not occurred over a 4 week titration period. Subjects then received treatment over a 24 week maintenance phase followed by a de-escalation over a period up to 12 days. Mean baseline combined UPDRS was similar across all groups (33.2 Neupro, 245 31.3 placebo, 32.2 comparator). Neupro treated subjects experienced a mean change in the combined UPDRS from baseline to end of treatment of - 6.83, and placebo treated subjects showed a mean change from baseline of - 2.33, a statistically significant difference.

Adverse events associated with the use of Neupro may include, but are not limited to, the following:

• Somnolence
• Nausea
• Application site reactions
• Dizziness
• Headache
• Fatigue
• Extremity edema
• Insomnia

Neupro is a transdermal delivery system that provides rotigotine, a non-ergoline D3/D2/D1 dopamine agonist, continuously over a 24-hour period. The exact mechanism of action of rotigotine in the treatment of Parkinson's disease is unknown. However, it is thought to be related to its ability to stimulate dopamine D2 receptors within the caudate-putamen in the brain.

LeWitt PA, Lyons KE, Pahwa R; SP 650 Study Group Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology 2007 Apr 17;68(16):1262-7

Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Nuerology 2007 Jan 23;68(4):272-6

Babic T, Boothmann B, Polivka J, Rektor I, Boroojerdi B, Hack HJ, Randerath O Rotigotine transdermal patch enables rapid titration to effective doses in advanced-stage idiopathic Parkinson disease: subanalysis of a parallel group, open-label, dose-escalation study. Clinical neuropharmacology 2006 Jul-Aug;29(4):238-42

Guldenpfennig WM, Poole KH, Sommerville KW, Boroojerdi B Safety, tolerability, and efficacy of continuous transdermal dopaminergic stimulation with rotigotine patch in early-stage idiopathic Parkinson disease. Clinical neuropharmacology 2005 May-Jun;28(3):106-10

The Parkinson Study Group A controlled trial of rotigotine monotherapy in early Parkinson's disease. Archives of neurology 2003 Dec;60(12):1721-8

For additional information regarding Neupro or Parkinson's disease, please visit the Neupro web page.