Tuesday, 13 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S81–S159 S133
showed that saﬁnamide 100 mg/day improved DRS scores in
patients with more severe dyskinesia at baseline.
Study supported by: Newron/Merck Serono S.A. – Geneva.
SAFINAMIDE AS ADD-ON TO LEVODOPA IN PARKINSON’S DISEASE
WITH MOTOR FLUCTUATIONS MAY IMPROVE RESPONDER RATES
VERSUS PLACEBO DURING LONG-TERM TREATMENT
, C. Meshram
, J. Szasz
, M. Bhatt
, R. Guiliani
, for the Study 018 Investigators.
APC AG, St Moritz,
Brain and Mind Institute, Nagpur, India;
County Hospital, Targu Mures, Romania;
Jaslok Hospital & Research
Centre, Mumbai, India;
Newron Pharmaceuticals SpA, Bresso, Italy
Objective: To determine the clinical relevance of the long-term
beneﬁts of saﬁnamide, an a-aminoamide with dopaminergic and
non-dopaminergic mechanisms, as add-on to levodopa.
Methods: Previous analyses from Study 018 (n = 544), an 18-month,
double-blind, placebo-controlled extension to Study 016 (6 months;
n = 669), which evaluated saﬁnamide (50 or 100 mg/day) added
to levodopa in patients with Parkinson’s disease (PD) and motor
ﬂuctuations despite optimized therapy, showed that saﬁnamide
100 mg/day had beneﬁts on ON and OFF time, UPDRS Part II/III/IV,
PDQ-39, and GRID HAM-D scores, but no signiﬁcant effect on
Dyskinesia Rating Scale (DRS) scores versus placebo. The present
analysis was performed to determine the clinical relevance of
these effects by evaluating responder rates. A hierarchical testing
procedure was implemented: if the primary endpoint (change
in DRS scores) was not met, key secondary endpoints were of
exploratory nature only.
Results: After 24 months, saﬁnamide improved responder rates
for a number of evaluations, including increase in ON time and
decrease in OFF time with no worsening of troublesome dyskinesia
(placebo [n = 222] 39.2%, 50 mg/day [n = 223] 45.3% [p = 0.1710] and
100 mg/day [n = 224] 49.6% [p = 0.0100]), and for ≥30% improvement
in UPDRS Part III with no worsening in UPDRS Parts II or IV
(placebo 21.6%, 50 mg/day 27.4% [p = 0.1002] and 100 mg/day 30.8%
[p = 0.0059]).
Discussion: Two-year treatment with saﬁnamide in mid-
late PD patients with motor ﬂuctuations despite optimized
antiparkinsonian therapy was associated with improvements in
responder rates that may be clinically important.
Study supported by: Newron/Merck Serono S.A. – Geneva
BUPROPION ON FREEZING OF GAIT IN PARKINSON’S DISEASE
, W.C. Kim
Dept.of Neurology, CHA
Bundang Medical Center, CHA University, Seongnam-si, Republic of
Objective: To evaluate effects of bupropion on freezing of gait (FOG)
in patients with idiopathic Parkinson’s disease (PD).
Background: FOG is one of the most disabling problems in
PD. The underlying pathophysiology of FOG is not understood
completely yet. Because of poor responsiveness of FOG to
dopamine replacement treatment, it is widely accepted that non-
dopaminergic neurotransmitters associated with pathophysiology
of FOG in PD. Bupropion, a norepinephrine-dopamine reuptake
inhibitor, seems to be a reasonable choice for the treatment of FOG
from a theoretical point of view.
Methods: PD patients who showed FOG on examination while best
“on” phase were included. We performed an open-label 12-week
trial. Treatment with bupropion was initiated with 150 mg/day, and
increased up to 300 mg/day the next week. This was followed by
a 10-week ﬁxed-dose maintenance phase, during which all the
patients were maintained on bupropion at 300 mg/day. Enrolled
participants were evaluated with the Gait and Balance Scale (GABS)
score before and after 12-week bupropion treatment.
Results: Nine PD patients with FOG were enrolled prospectively.
All patients showed disabling FOG in spite of appropriate dose
of dopamine treatment. The mean GABS total score was reduced
after the 12-week trial (30.4±3.5) compared with the baseline
(34.5±5.0), but did not reach the statistical signiﬁcance.
Conclusions: Bupropion was not efﬁcacious for the treatment of
FOG in patients with PD. Large, double-blind, placebo-controlled,
randomized trials may be helpful to show the efﬁcacy of bupropion
on FOG in PD.
DEVELOPMENT OF INHALED APOMORPHINE FOR PATIENTS WITH
FLUCTUATING PARKINSON’S DISEASE: DOSE-FINDING RESULTS
, K. Grosset
, F. Morgan
, Inhaled Apomorphine Study
Neurology, Inst of Neurol Sciences, Glasgow,
plc, Chippenham, UK
Background: Subcutaneous apomorphine injection is established
as an intermittent treatment for OFF periods in Parkinson’s disease
(PD). Clinical dose ranging of a rapidly acting and non-invasive
inhaled apomorphine has been conducted.
Methods: Inhaled apomorphine was tested in two separate
randomised, double-blind, placebo-controlled, dose-ascending
Phase 2 clinical studies until efﬁcacy or adverse events occurred.
Response to in-clinic doses of 1.5 to 4.0 mg (Study 1) and 1.5 to
4.5 mg (Study 2) was compared to a Levodopa challenge test. Out-
patient testing was performed (Study 2) with changes in OFF and
ON time measured.
Results: 102 patients received study treatment, at an approximate
2.5:1 active: placebo ratio. Rapidly absorbed apomorphine (t
of 2 minutes) resulted in therapeutic beneﬁt 5–10 minutes post
inhalation with some subjects converting to the ON state 1 minute
post dose. In-clinic UPDRS 3 reduction was signiﬁcantly greater
for apomorphine than placebo in both studies: Study 1 treatment
difference 11.6 points (95% conﬁdence interval (CI) 2.3–20.9,
p = 0.016; Study 2 treatment difference 8.4 points, CI 1.2–15.5,
p = 0.023. Study 2 at-home OFF time reduction for apomorphine
was greater than placebo (100.5 minutes, 95% CI −12.0–212.9) but
was not statistically signiﬁcant (p = 0.078). Tolerability was good;
adverse events were consistent with dopaminergic stimulation
(nausea, blood pressure change). Only 4 patients ascended to the
4.5 mg dose, at which additional beneﬁt was minimal and adverse
events were more frequent.
Conclusion: Inhaled apomorphine showed promising efﬁcacy,
safety and tolerability at doses between 1.5 and 3.5 mg.
THE TREATMENT OF PAINFUL DIAPHRAGMATIC DYSTONIA IN
IDIOPATHIC PARKINSON’S DISEASE WITH APOMORPHINE
A. Ross Russell, M. Silva. Neurology, Gloucestershire
Hospitals NHS Foundation Trust, Gloucester, UK
Case report: A 46 year old male was diagnosed as having Idiopathic
Parkinson’s Disease. He responded well initially to Pramipexole,
Madopar, Stalevo and Selegiline with the emergence of dyskinesias
and wearing off six years later. However, eight years after diagnosis
he developed intermittent episodes of painful dyspnoea related
to off phases. No other chest pathology was identiﬁed. The
relationship to dopaminergic medication suggested a diagnosis of
Manipulation of oral PD medication was ineffective but there
was a clear and signiﬁcant improvement following treatment
with subcutaneous apomorphine. Quality of life was signiﬁcantly
Conclusion: Apomorphine can be an effective way of treating
painful diaphragmatic dystonia in PD.