PI.t30 /
A Multinet Trial Comvarina the Efficacy, Talerability. and Safety of
=09=B7=09=B7=09=B7=09* ,.
TalcatOne vs Pemolide in Parkmson's Patients with Motor Flucmatwn, W I~lle=
r*,
A Lees, J Morris, A Stetman               .    .. '~-ansas City, KS, Londo=
n,
UK, Sidney, Australia, and Nuttey, mJ
In a parallel-groups trial patients were randomized to tolcapone (N =3D
102) or pergolide (II =3D 101). Patients had fluctuations despite optimal
and stable levodopa doses. Efficacy was evaluated by patient diaries and
UPDRS scales by a blinded rater. Efficacy ratings, made at 4 and 12
weeks included change in percent "off" time, UPDRS subscales II, III,
and investigator's global. The two groups had comparable baseline
characteristics. Patient dropouts occurred in 11% of the tolcapone-
treated patients and 20% of pergolide-treated patients. Dropouts for
adverse events occurred in 5% tolcapone vs 15% pergolide patients.
Both treatments decreased percent "off" time relative to baseline: 18% vs
16%, Tolcapone vs pergolide. UPDRS subscales (II, III, and II + III)
improved with both treatments, but tolcapone was numerically favored.
by 0.3 to 0.9 points. The investigator's global rating of overall efficacy
showed "improvement" in 86% tolcapone vs 78% pergolide; the global
assessment of overall tolerability showed "improvement" in 77%
tolcapone vs 59% pergolide. Among clinically important adverse events
=09=B7=09--~,~ed in 1% vs 7%, and confusion in 4% vs
=09(AEs), hypertension was,cH--
=0910%, tolcapone vs pergolide. Other notable AEs were defined by greater
=09than 5% incidence and at least 1.5 times more common in either group.
=09,=09=B7=09.=09=B7 ,,
=09In tolcapone these notable AEs were dystoma and unne discoloration, m
=09pergolide they were nausea, constipation, abdominal discomfort, and
=09dyspepsia. In summary, both tolcapone and pergolide provide patient
=09efficacy, but the two drugs differ in A.Es and Talerability.

=09.142=09/                         .=09.     , j .=09.

Influence of C=09--    2 =09a:-3 C Sv~'A,,=A2n2, UK Pinnet
--=09=B7=09,I IU anen,P~uo,um,- J-
HM Ruottmen , [J~h =09,.. .r,,,t-,-    arqet Protein
=09..=09, i. ---iversi"' oi tu~,~, -~.-- T ~
Inept of meuro~Y, ~L, ' ^-.~- Oho,-,,a, shoo. Finland
Lal~o~-~m~Researctx center, who =09E ~.

Enzyme catechol. O-methyltransferase (COMT) is coded by one gene The 11 th=
at
occurs as two polymorphic alleles: a high activity allele
(22q ) =09toc~xATt.~ Individuals with genotype
(COMTH) and low activity eate~c ~. =09=B7
=09COMTLc have low, and those with CaMT~ have high enzyme activity,
=09while heterozygous subjects CaMTm have intermediate COMT activity.
=09The distribution of activity is similar in the general population and i=
n
=09Parkinson's disease (PD) patients=B7 The aim was to correlate COMT
=09genotypes with motor response to levodopa without and with the COMT
=09inhibitor entacapone in PD patients with end-of-dose fluctuations. Thir=
ty-six
=09PD patients were gcnotyped for COMT polymorphism. The duration of
=09motor response to levodopa ~: entacapone (ON time) w.as asses~d in
=09double-blind manner with the motor part of the Unified parkinson's Dise=
ase
=09Rating Scale during the levodopa test=B7 On test days the patients rece=
ived a
=09single 200-rog dose of entacapone or placebo along with their individua=
l
=09morning dose of levodopa- Six patients had CaMT~, six COMT LL and 24
=09COMTm genotype. The erythrocyte COMT activity was highest in the
=09COMT~ group The duration of motor response to levodopa at baseline was
=09slightly lower m the camT~ group than in the other groups. The increase
=09in ON time was three times lower (10 rain v 30-31 min) and increase in
=09duration of dyskinesias was lowest (0 min v 35-37 rain) in the COMTLL
=09=B7 =B7 'on cam ared with the COMT~ and
=09or o after entacapone admires,u~au=09P =09that the CaMTO'
=09~,-ou.=09.=09,---:--- +here seems to t~ ,~ u~nd
=09COMT m groups, m concm~sv-, ~'
=09group differed from the cambium and COMTm groups regarding increase
=09in Obi time and duration of dyskinesias after COMT inhibition. Due to t=
he
=09small number of patients the difference was not statistically significa=
nt.
For
=09valid conclusions a larger study is needed.
/P3
127
'"'~ xX,
[=09The effect o~ ent.t-~none, a nerioheral COMT inhibitor, and sele~iline
\=09on sleek in ]~,-dooa-treated patients with Parkinson's Disease (PD)
\=09J Lyytinel~, S Kaakkola, H Te~v~linen, A Gotdin . . .
=09Dep~nt of Neurology, University of Helsinld, Helsinki, Finland and
=09'Dt,~Corp., Orion Pharma., Espoo, Finland
Sleep is often profoundly disturbed in PD. This may be due to both disease=
-and
treatment related factors, eg. inadequate Ldopa coverage at night=B7 Seleg=
iline
is also known to cansc sleep difficulties. Entacapone is a catecbol-O-
methyltransferasc (COMT) inhibitor, which reduces COMT-related elimination=
 of
peripheral Ldopa and inetcmos its bioavailability in PD patients. We studi=
ed
thc effects of entacapone (E) and selegiline (S) on sleep duration and
quality, when administercci as Ldopa (LD) adjuncts to 14 PD patients in a
randomized, double-blind, controlled study. The assessments were made firs=
t on
LD only (control), then after two-weeks of LD with i) E (200 nag with each=
 LD
dose), ii) S (10 mg o.d.) and iii) E+S. At thc end of treatments, sleep wa=
s
assessed using an ambulatory wrist-worn activity monitoring device
(Actigraf'). The duration of and motor activity during sleep were calculat=
ed.
The patients also self-evaluated their sleep.
There were no significant differences in the duration of (6.3+ 1.2 h for
control; 6.5+1.1 with E+LD; 6.2+1.3 with S+LD and 6.7+1.4 with E+S+LD) or =
in
the mcan motor activity (cantwi: 44+39 counts, E+LD: 48+33, s+LD: 44+30 an=
d
E+LD: 47+33) during sleep between treatments. However, insomnia was report=
ed
by two (13 %) and four (25%) patients after S+LD and E+S+LD, respectively.
After E+LD, more patients gave the best score for sleep quality and length
than with any other treatment and none reported insomnia.
Our results suggest, that sleep does not deteriorate during administration=
 of
E and S with LD, although subjective reports of disturbed sleep seem relat=
ed
to S, but not to E, which, in fact, might have beneficial effects.

=09A double-blind trial of tolcauone Qn Chtn~so
=09Dat/4~nts with parkin~on,s dis~a~-
=09Shall* & SI Yeh ~=09=09~ ~'
=09Neurological Institute,=09Veterans General
=09Hospital - Taipei, & National Yang-Ming
=09University School of Medicine, Taiwan, R0C
=09e
=09,r=09Forty patients with wearing-off phenomenon
=09=09completed a randomized, double-blind,
=09I[=09placebo-controlled trial of tolcapone. After
=09=09a screening period of 2 weeks,
tolcapone/placebo was given for a period of 6 weeks. The efficacy on final
visit was compared with that on baseline. While most patients in both grou=
ps
received 600 mg/day, 5 out of the 20 patients in the tolcapone group recei=
ved
300 mg/day due to marked
=09improvement of efficacy=09or worsening of
=09dyskinesia. There was a=09tendency for the
=09dosage ( -4.6% vs. -1%)=09or the frequency
=09(-0.25 vs. 0) of Madopar and the UPDRS motor
=09scores during on-period (-18.1% vs. -12.7%)
=09to decrease in the tolcapone group (p>0.05).
=09The UPDRS motor scores during off -period
=09(-26.3% vs. -14.6%) decreased significantly
=09in the tolcapone group (p<0.05) . The
=09percentage of off time (-43.5% vs. 3.3%) also
=09decreased significantly in the tolcapone
=09group (p<O. 05 ) . More patients in the
=09tolcapone group (7 vs. 1) had worsening of
=09dyskinesia (p<0.05), which became less severe
=09after the dosage of Madopar was reduced. In
=09conclusion, tolcapone is a very effective
=09agent for advanced Parkinson,s disease.