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


Neil Osterweil
1/4/07(Medpage) -