We may still be a long way off
from stopping the progression of Parkinson's disease
(PD) but there's now the promise of a simpler way to
control its symptoms, following the phase III trial
of the non-ergoline dopamine agonist rotigotine, in
transdermal patch form.
Research published in Neurology
showed rotigotine achieved significant reductions in
scores on the Unified Parkinson Disease Rating Scale
(UPDRS), with the improvements concentrated in the motor
control and activities of daily living sections. "This
study showed that rotigotine may be safe and effective,
and potentially be of major value in the treatment of
early-stage PD," lead study author Ray Watts, a neurologist
at the University of Alabama in Birmingham, said in
a press release. "It seems to offset the variability
we often see in the multiple dose regimens of other
drugs."
BETTER,
FASTER
The placebo-controlled trial involved 277 patients with
early PD across Canada and the US. Ninety-six were randomised
to take placebo, while 181 wore rotigotine patches administering
2, 4, or 6mg over 24 hours.
After six months, patients taking
rotigotine scored an average of 3.98 points lower on
the UPDRS than at baseline. Conversely, patients taking
placebo saw a 1.31-point increase, for a difference
of 5.28 points in favour of rotigotine.
Plotted over time, the UPDRS scores
in both groups followed an all too familiar trend. At
the outset, symptom severity declined rapidly in both
groups, with all patients achieving their lowest scores
by the six-week mark. Then, the scores started to slowly
climb back up.
But the initial improvement in
the rotigotine group was much more pronounced, and the
apparent wearing off of the effect was slower, so that
at six months, while the drug seemed to be getting less
effective, symptom scores were still much better than
at the outset.
CONSTANT
IMPROVEMENTS
Data on longer-term effectiveness will have to await
the results of a three-year open-label extension to
this trial. The researchers are particularly anxious
to learn if the drug will delay the onset of motor complications.
They have some reason to be optimistic
on this score. Two other dopamine agonists commonly
used for treating early PD, pramipexole and ropinirole,
are both able to delay the onset of motor complications.
So it's entirely plausible that rotigotine will do the
same.
If that's the case, it may offer
an added benefit over the other two - 24-hour continuous
drug delivery. Pramipexole and ropinirole have half-lives
of six to eight hours, so these oral, three-a-day regimens
are likely to leave the patients experiencing some peaks
and troughs.
"Since the responsiveness of shorter
acting drugs now used to treat PD becomes more variable
as the disease progresses over time, the transdermal
patch may have advantages because of the continuous
delivery of the therapy, which avoids the abrupt 'off'
state that can occur with other therapies," Dr Watts
said.
The rotigotine patch caused occasional
application site reactions. But these were fewer than
seen in nicotine patch trials, the authors say. The
best evidence of good overall tolerability is that most
patients moved quickly to the maximum strength 6mg patch
and stayed there, with the average patch strength in
the whole group being 5.7mg.
The other dopamine agonists are
sometimes also used in more advanced Parkinson's to
supplement and partially substitute for levodopa. A
trial is planned for this indication for rotigotine
too, using 8 and 12mg patches. The drug is also likely
to have a profitable sideline in restless legs syndrome,
like its cousin ropinirole.
The transdermal rotigotine patch
has already been approved in Australia and some European
countries. If it hits the market here, it will come
in starter packs with a range of dosages to allow titration.
Prices are likely to be in the $15-$30 range each depending
on dosage.
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