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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.