June 23, 2016
BERLIN -- An extended-release
formulation of amantadine for levodopa-induced dyskinesia is well tolerated in
the long run, researchers reported here.
In an interim analysis of data
from an ongoing open-label safety study, adverse event rates for those on
ADS-5102 were similar to those in earlier studies over a total of 41 weeks,
with the most common being falls (20%) and hallucinations (11%), Rajesh Pahwa, MD,
Director of the Parkinson's Disease and Movement Disorder Center at the
University of Kansas Medical Center, and colleagues reported at the International Congress of
Parkinson's Disease and Movement Disorders.
For
the side effects profile, the numbers aren't any different," Pahwa told MedPage
Today. "The benefit is maintained long-term, and people
tolerate the drug very well."
Amantadine
is an old drug for Parkinson's disease that has been used to treat
levodopa-induced dyskinesia, but it has to be taken two to three times a day,
and its effects are not lasting, explained Claudia
Trenkwalder, MD, of the University of Gottingen in Germany, who was
not involved with the study.
Adamas
Pharmaceuticals, therefore, developed a long-acting, extended-release version
that can be taken before bedtime, before early-morning levodopa starts to
produce dyskinesia, she explained: "This may be helpful and more efficient
if you can give it at night as a sustained-release that works all day
long," she told MedPage Today.
The
EASE LID 2 trial was an open-label safety study conducted at 56 centers in
North America and Western Europe. All patients either continued or started the
340-mg dose of ADS-5102 after the initial 24 weeks of the study, and the
interim analysis also included data from patients with deep brain stimulation
who still had levodopa-induced dyskinesia but had not been in the earlier
trial.
The
primary outcome was safety and tolerability, but the researchers also looked at
efficacy as measured on the Unified Parkinson's Disease Rating Scale (UPDRS)
Part IV, Pahwa said.
Overall,
129 patients had at least one post-baseline visit prior to the data cutoff
date.
The
researchers found rates of complications that were similar to those of the
initial study, although patients who had originally been on placebo had
slightly higher adverse event rates, which was expected, Pahwa said.
Discontinuation
was also higher for those who had been on placebo initially compared with those
who continued the study drug (17.6% versus 3.6%), which was also expected.
The
most common adverse events overall were falls (20.2%), visual hallucinations
(11.6%), abnormal dreams (7%), dizziness (7%), peripheral edema (7%),
constipation (5.4%), and dry mouth (5.4%).
There
was one urinary tract infection that was deemed to be drug-related, and the two
deaths in the study were not thought to be related to extended-release
amantadine, the researchers reported.
n
terms of efficacy, the reductions on the UPDRS Part IV that were seen at the
end of the randomized controlled trial were maintained in the follow-up period,
and those who switched from placebo caught up to those who were on the drug the
entire time, Pahwa said.
UPDRS
scores were reduced from baseline by an average of 6 points for those who had
been on placebo and by 6.6 points for those who had been on active drug. These
reductions were driven by improvements in two items on the scale: functional
impact of dyskinesia and functional impact of fluctuations, Pahwa said.
He
added that the benefits were achieved without compromising the underlying
control of Parkinson's symptoms, and concluded that the results demonstrate the
long-term safety and efficacy of extended-release amantadine.
Adamas
previously completed two pivotal phase III trials and is actively planning to
file a New Drug Application with the U.S. Food and Drug Administration,
according to a company spokesperson, although they would not disclose a
timeline.
Trenkwalder
noted that several other compounds have been evaluated for treating
levodopa-induced dyskinesias, but this is one of the first to demonstrate
safety and efficacy in phase III trials.
"It's
difficult to measure dyskinesia, but this study relied on home diaries and
succeeded," she said.
http://www.medpagetoday.com/MeetingCoverage/MDS/58734?xid=nl_mpt_DHE_2016-06-24&eun=g972365d0r
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