Rotigotine Does Not Prolong QTc Interval in Patients With Advanced Parkinson's Disease: Presented at ACCP

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Title: Rotigotine Does Not Prolong QTc Interval in Patients With Advanced Parkinson's Disease: Presented at ACCP
URL: http://www.pslgroup.com/dg/22C80A.htm
Doctor's Guide
September 16, 2008

By Maggie Schwarz

PHILADELPHIA -- September 16, 2008 -- Rotigotine does not influence cardiac repolarisation in patients with advanced Parkinson's disease (PD), even at a supratherapeutic dose, according to research presented here at the American College of Clinical Pharmacology (ACCP) 37th Annual Meeting.

Marina Braun, MD, Schwarz Biosciences GmbH, Manheim am Rhein, Germany, and colleagues presented the results of a QT/QTc study in a poster session on September 15.

Rotigotine is a non-ergoline dopamine receptor agonist formulated for once-daily transdermal administration. The drug possesses a unique receptor profile with activity across the D1 through D5 dopamine receptors as well as select adrenergic and serotonergic sites. It has been demonstrated to be effective for early-stage idiopathic PD and as an adjunct to levodopa for advanced PD.

Since high doses of dopamine receptor agonists cannot be given to healthy subjects due to adverse events (for example, nausea, vomiting, hallucinations), this thorough QT study was conducted among patients with advanced PD. The study was conducted over a dose range exceeding the anticipated highest therapeutic dose in advanced PD.

The double-blind, randomised, placebo- and positive-controlled, parallel-group trial enrolled 130 patients with advanced PD who were taking a stable dose of levodopa and were randomised to placebo (n = 64) or rotigotine (n = 66).

Patients were a mean of 63.3 years (range, 29-88 years) and 68.5% were male.

The rotigotine dose was escalated over 6 weeks from 4 to 24 mg/24 h, at weekly increments of 4 mg/24 h, followed by dose de-escalation over 10 days, with daily doses decreased by 4 mg/24 h every 2 days. A safety follow-up period of 2 weeks followed the treatment period. Rotigotine and corresponding placebo transdermal patches were applied every evening.

All patients were assessed for 12-lead standard electrocardiography (ECG), vital signs, and laboratory parameters.

Mean differences between rotigotine (<=24 mg/24 h) and placebo in time-matched changes from baseline in QTc interval at each individual time point were similar and close to 0 ms.

Rates of patients having at least 1 adverse event were 96% in the rotigotine group and 84% in the placebo group.

Five adverse events were reported in the rotigotine and the placebo groups at an incidence of ≥20%: nausea (42% vs 22%, respectively), headache (30% vs 25%), dizziness (20% vs 9%), vomiting (23% vs 5%), and site reactions to the ECG electrodes (23% vs 22%).

No clinically relevant effects on laboratory parameters, ECG, or vital signs were noted in either group.

The investigators concluded that rotigotine exposure at supratherapeutic doses of 24 mg/24 hours did not induce QTc prolongation in this cohort of patients with advanced PD.

Dr. Braun stated, "the study was the first of its kind in advanced PD, and as such, was challenging because patients were elderly and had concomitant illnesses."

[Presentation title: Conduct of a Thorough QT/QTc Study With a Transdermal Dopamine Agonist in Patients With Advanced-Stage Parkinson's Disease. Abstract 72]

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