in a linear manner with increasing dose [AUC t (mg-h/mL; mean 6 SD) for 0.15 mg/kg: 1260 6 254, 0.5 mg/kg: 4264 6 462, 1.0 mg/kg: 7818 6 652, 2.0 mg/kg: 15313 6 8478]. Mean t 1/2 ranged from 15.0 to 28.1 days. Bapineuzumab clearance was similar across dose groups (range: 0.12 - 0.17 mL/h/kg). Plasma Aß x-40 levels increased with increasing doses of bapineuzumab (Fig. 2). No anti-bapineuzumab antibodies were found in any of the samples tested. Conclusions: Bapineuzumab was generally safe and well tolerated at doses of 0.15 mg/kg, 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg in Japanese patients with mild to moderate AD. The pharmacokinetic profile of bapineuzumab in Japanese patients is consistent with that observed in other studies with non-Japanese patients. P4-211 TREATMENT OF ALZHEIMER’S DISEASE WITH TRANSDERMAL RIVASTIGMINE: THE ROLE OF PRECEDING AND CONCOMITANT MEDICATION Konstantin Articus 1 , Stefan Spittler 2 , Johannes Seibert 3 , Klaus Hechenbichler 4 , Klaus Bornholdt 5 , Peter Sch€ onknecht 6 , 1 Novartis Pharma GmbH, Nuremberg, Germany; 2 Alexianer-Krankenhaus, Krefeld, Germany; 3 Outpatient Clinic, Heidelberg, Germany; 4 Institut Dr Schauerte, Oberhaching, Germany; 5 Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 6 Universit€ atsklinikum Leipzig, Leipzig, Germany. Background: Alzheimer’s disease (AD) often comes along with medi- cation changes and concomitant use of psychotropic drugs to manage behavioral symptoms. The current study aimed to explore in daily prac- tice (a) the effect of rivastigmine patch on co-medication use and (b) the impact of pre-treatment on its effectiveness. Methods: This was a prospective, multi-centre, non-interventional study in 1113 patients across Germany. Eligible were patients with AD not previously treated with oral rivastigmine. Once initiated on rivastigmine patch, they were followed for 4 months regarding the clock drawing test (CDT), the Mini-Mental State Examination (MMSE), the caregiver burden scale (CBS), their overall medical condition, treatment adherence, and use of co-medication. Results: At baseline, 58% of patients were treated for AD for the first time whereas 42% changed therapy. Pre-treated as compared to not pre-treated patients tended to escalate earlier to the target dose of 9.5 mg/day (after 1 month 61% versus 55%), to re- main longer in the trial (drop out rates after 4 months 5.6% versus 9.0%), and a higher proportion was on the target dose after 4 months (71% versus 65%); however, all these differences were not significant. Under rivastigmine, MMSE and the overall medical condition signifi- cantly improved, regardless of pre-treatment (after 4 months MMSE, 0.8 6 3.4 pre-treated versus 0.9 6 3.4 not pre-treated; improved med- ical impression, 61.3% versus 60.9%, both not significant). Under riva- stigmine the proportion of patients taking psychotropic co-medication decreased from 29.0% to 25.8%. However, this decrease was more pronounced and became significant in patients who had not been pre- treated (from 27.1% to 22.6%; p < 0.001). Conclusions: Pre-treatment of AD with antidementive drugs does not appear to have major impact on the effectiveness of transdermal rivastigmine but may influence the use of psychotropic co-medication. This warrants confirmation in controlled clinical trials. P4-212 EXPECT (EXELON PATCH EFFECTIVENESS TRIAL): EFFECTIVENESS AND TOLERABILITY OF TRANSDERMAL RIVASTIGMININ DAILY PRACTICE Konstantin Articus 1 , Klaus Hechenbichler 2 , Klaus Bornholdt 3 , 1 Novartis Pharma GmbH, Nuremberg, Germany; 2 Institut Dr. Schauerte, Oberhaching, Germany; 3 Sanofi-Aventis Deutschland GmbH, Berlin, Germany. Background: Cholinesterase inhibitors are a mainstay in the treatment of dementia associated with Alzheimer’s disease (AD). Efficacy increases with dose, however high oral doses may entail side effects requiring their cessation. In controlled clinical trials, transdermal rivastigmine showed similar efficacy at improved tolerability as compared to oral formula- tions. EXPECT aimed to verify this under daily routine conditions. Methods: EXPECT was a prospective non-interventional study in outpa- tient clinics across Germany. Enrolled were AD patients whom their treating physician deemed eligible for treatment with rivastigmine patch and who had not previously received the oral formulation. Endpoints were the clock drawing test (CDT), the Mini-Mental State Examination (MMSE), the caregiver burden scale (CBS), and the physicians’ assess- ment of tolerability and effectiveness over a period of 4 months. Results: 498 centers enrolled 1113 patients (44.8% men, mean age [SD] 76.5 [7.5] years); 646 were treated for AD for the first time whereas 466 changed therapy, 151 and 299 of them due to lacking tolerability and effectiveness of pre-treatment, respectively. After 4 months, 67.4% of patients received the target daily dose of 9.5 mg rivastigmine and showed no deterioration in clinical endpoints (CDT, means [SD]: 3.2 [2.0] vs. 3.5 [2.2]; MMSE: 18.1 [5.7] vs. 18.8 [5.9]; CBS, A: 18.4 [6.1] vs. 17.3 [5.9], B: 15.8 [6.5] vs. 15.2 [6.1]). The overall medical impression had im- proved in 61.1%, remained unchanged in 28.9%, and aggravated in 3.1% of patients according to their physicians who in 5.9% of cases as- sessed tolerability as poor. 164 (14.7%) patients prematurely discontin- ued medication, 67 (6.0%) of them due to adverse events. 104 patients (9.4%) showed mainly dermatological (47.6%) or gastrointestinal (23.8%) side effects; in 12 patients those were serious and mostly linked to MedDRA System Organ Classes psychiatric (50%) und neurological (15.4%) disorders. Conclusions: Rivastigmine patch might offer an effec- tive treatment alternative, particularly in patients with lacking tolerability of oral target doses. P4-213 EFFECTS OF 6-MONTH MONOTHERAPY TREATMENT WITH THE 5HT6 RECEPTOR ANTAGONIST SB 742457 OR DONEPEZIL IN SUBJECTS WITH MILD-TO-MODERATE ALZHEIMER’S DISEASE Gareth Maher-Edwards 1 , Marina Zvartau-Hind 1 , John Davies 1 , Kurz Alexander 2 , Juan Schronen 3 , Diane Boswell 1 , John Ascher 4 , Michael Gold 4 , 1 GlaxoSmithKline, Uxbridge, United Kingdom; 2 Technische Universitaet Muenchen, Munich, Germany; 3 617 Tyger Valley Healthcare, Capetown, South Africa; 4 GlaxoSmithKline, Research Triangle Park, North Carolina, United States. Background: SB-742457 is a novel and potent 5-hydroxytryptamine 6 (5 HT6) receptor antagonist that enhances cognition in preclinical models and has demonstrated some improvement in global outcome and cognition in clinical trials. Methods: In this 24-week, double-blind, randomised, study (AZ3110865), 574 currently untreated subjects with mild-to-moderate (MMSE 10-26) probable Alzheimer’s disease (AD) re- ceived SB-742457 15 mg/day, (n ¼ 145); 35 mg/day, (n ¼ 133); donepezil 5-10mg day (n ¼ 151); or placebo (n ¼ 145). The co-primary efficacy Figure 2. Mean Ab x-40 plasma concentrations Presentation P4 S777