BOSTON—Apomorphine may provide relief from off time for people with advanced Parkinson’s disease, according to a study presented at the 69th Annual
Meeting of the American Academy of Neurology.
“If a person with Parkinson’s disease can reduce their
off times, that can have a great impact on their everyday
life,” said study author Regina Katzenschlager, MD, of
Danube Hospital, which is affiliated with the Medical
University of Vienna. “In some patients in the trial, the
insecurity of unpredictable periods of incapacity was
Open-Label Data Suggest Efficacy
Levodopa has long been the gold standard in the treatment of Parkinson’s disease, but the effects of the
medication can partially wear off more quickly as the
disease progresses. Patients consequently experience
off time that includes symptoms such as slowness and
The drug apomorphine, which first was produced in
1865, began to be used to treat advanced Parkinson’s
disease in the United States in 1950. Its use grew in the
1990s when European doctors started administering
subcutaneous infusions of the drug to treat fluctuations
in mobility that could not be controlled by levodopa.
Extensive data from open-label studies of apomorphine have demonstrated its efficacy in reducing off
time, dyskinesias, and oral levodopa dose in patients
with severe motor fluctuations that are poorly controlled
by conventional therapy. Evidence from randomized,
blinded studies of the drug has been lacking, however.
Comparing Apomorphine With Placebo
In a double-blind phase III study, researchers recruited
107 people with advanced Parkinson’s disease from 23
centers in seven countries. Participants were randomized
to either apomorphine subcutaneous infusion (≤ 8 mg
/h) or a placebo saline infusion. The infusion was ad-
ministered over a period of 14 to 18 hours each day
through a small portable pump similar to the type used
in the treatment of type 1 diabetes. The hourly flow
rate of the infusion and dose of concomitant antiparkin-
sonian medication were adjusted during the first four
weeks, based on efficacy and tolerability. The study’s
primary end point was the absolute change in off time
from baseline to Week 12 based on patient diaries.
Patients who received apomorphine had a signifi-
cantly greater reduction of off time than those who
received the placebo infusion. Active patients had, on
average, 2. 5 hours less off time per day, while partici-
pants who received the placebo infusion had an average
of 35 minutes less off time per day. This improvement
was apparent within the first week of treatment and was
sustained over 12 weeks. At the same time, patients
who received apomorphine had a significantly greater
increase of on time without the dyskinesias that often
are observed with levodopa, compared with placebo.
Participants were also asked to evaluate how well
they thought the treatment worked. Those who received
apomorphine gave their treatment higher scores at week
12 than those who received the placebo infusion. In
the apomorphine group, 71% of patients felt improved,
compared with 18% of patients who received placebo.
Furthermore, 19% of patients worsened on apomorphine, compared with 45% on placebo. Apomorphine
was generally well tolerated, and the researchers observed no serious side effects.
“It is our hope that these findings confirming the efficacy of apomorphine infusion will encourage doctors in
the United States to offer this treatment to their patients
and assess its efficacy in their own clinical practice,”
Dr. Katzenschlager concluded.
The study was supported by Britannia Pharmaceuticals, the maker of apomorphine. NR
Off Time for People With
Advanced Parkinson’s Disease
Patients who received apomorphine reported improvements and were less likely to have
worsening of motor function.