June 16,2015
SAN DIEGO -- An inhaled formulation
of levodopa reduced breakthrough motor symptoms in Parkinson's disease patients
during periods when their oral levodopa therapy had worn off, researchers
reported here.
In a phase IIb study, patients on the
investigational drug CVT-301 had a significant reduction in Unified Parkinson's
Disease Rating Scale (UPDRS) Part III scores over 4 weeks compared with
placebo, Robert Hauser,
MD, of the University of South Florida Medical Center in Tampa, and
colleagues reported in a poster at the Movement Disorders Society meeting here.
"It can serve an unmet
need," Hauser told MedPage Today. "If it proves safe and
effective in phase III trials, it has the potential to be helpful."
"Off" episodes involve
re-emergence of motor symptoms such as an impaired ability to move, muscle
stiffness, and tremor; these occur because the effectiveness of oral levodopa
wanes before the next dose can safely be given. Current therapies for these
episodes, which affect up to half of all patients on levodopa, are limited, the
researchers said.
Since levodopa is the most effective
oral treatment for Parkinson's symptoms, the ability to bridge those periods
between doses could be useful, Hauser said.
For the study, the researchers
randomized 86 patients with Parkinson's disease to either the investigational
inhaled product or to placebo during a 4-week period. For the first 2 weeks,
patients took a 35-mg dose, and for the last 2 weeks they took the 50-mg dose.
All patients were on levodopa
therapy, and their mean intake was 770 mg/day, with an average "off"
time of 6 hours per day.
The primary outcome was change in scores
on the UPDRS Part III during "off" periods.
On average, patients used the
"rescue" levodopa or placebo about two times per day.
Hauser and colleagues found that the
drug significantly improved UPDRS Part III scores at all time points between 10
and 60 minutes after administration compared with placebo (P<0.05).
By the end of the 4-week study, mean
change in UPDRS Part III scores were significantly better for drug patients,
for both doses:
35 mg: -9.9 versus
-5.3, P=0.007
50 mg: -10 versus
-3.1, P<0.001
Patients also reported reductions in
"off" time -- by 1.1 hours/day with the 35-mg dose, and by a
significant 1.6 hours/day with the 50-mg dose.
There were more adverse events in the
drug group -- 47% versus 33% -- including dizziness, cough, nausea, and
anxiety, which could be tied to an excess of drug, but that would need further
study, Hauser said.
They concluded that inhaled levodopa
improves motor function as early as 10 minutes after administration, reduces
"off" time, and appears to be safe and well tolerated.
Drugmaker Acorda Therapeutics is
currently enrolling patients in a phase III trial of the drug.
Peter Jenner, MD,
of King's College London, said in a statement that the novel inhaled
formulation "appears to offer a further and novel route of administration
of levodopa that can be used to treat 'off' periods."
"My immediate thought is that it will offer an
alternative to rescue from 'off' periods currently achieved by subcutaneous
injection of apomorphine," Jenner said. "A noninvasive form of rescue
therapy will have utility and convenience for patients with Parkinson's disease
experiencing sudden 'off' and improve their quality of life."
http://www.medpagetoday.com/MeetingCoverage/MDS/52166
Reviewed by Rebecca Farber, MD Corinne Goldsmith Dickinson Center for Multiple Sclerosis, The Mount Sinai Hospital, New York, NY
LAST UPDATED
Primary Source
International Congress on Parkinson's Disease and Movement Disorders
Source Reference: LeWitt PA, et al "Inhaled levodopa (CVT-301) provides rapid improvement of OFF states in Parkinson's disease" MDS 2015; Abstract 260.
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