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P104 Dopamine agonists and demented Parkinson’s disease patients: Really a no go?
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Abstract / Basal Ganglia 1 (2011) 13–45
bradykinesia, and fall) and the attrition rates due to these AEs. Other safety assessments include the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III; incidences of any AE and of serious AEs; pulmonary function tests (PEF and FEV1); Schellong test; and Epworth Sleepiness Scale. Efficacy assessments include Mattis Dementia Rating Scale (MDRS); Neuropsychiatric Inventory (NPI-10); Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL); and the MHYS. Results: Patient enrollment was closed in April 2009 after 583 patients had been randomized to treatment. Thirty-two percent were women. At screening, patients had a mean age (standard deviation, SD) of 72.4 (6.31) years and a mean MMSE score of 20.9 (3.36). Mean (SD) safety and efficacy scores were: UPDRS Part III 29.7 (11.89); MDRS 109.6 (19.09); NPI-10 11.3 (11.62); ADCS-ADL 49.5 (17.29). The modal stage of the MHYS was 3 shown by 235 (40.3%) patients. Conclusions: The study population is representative of patients with PDD. The study is expected to add to the long-term safety data on treatment of PDD with rivastigmine, in particular the effect of rivastigmine on the underlying motor symptoms of PD. doi:10.1016/j.baga.2011.01.022
P103 AFQ056 treatment of levodopa-induced dyskinesias: Results of two randomized controlled trials D. Berg, J. Godau, C. Trenkwalder, K. Eggert, I. Csoti, A. Storch, H. Huber, M. Morelli-Canelo, M. Stamelou, V. Ries, M. Wolz, C.B. Schneider, T. Di Paolo, F. Gasparini, S. Hariry, M. Vandemeulebroecke, W. Abi-Saab, K. Cooke, D. Johns, B. Gomez-Mancilla (Tübingen, Kassel, Marburg, Biskirchen, Dresden; Québec, CA; Basel, CH; High Wycombe, UK) Background: Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesias (LIDs). Methods: Two randomized, double-blind, placebo-controlled, parallel-group, inpatient studies for PD patients with moderate-to-severe (Study 1) and severe LIDs (Study 2) on stable dopaminergic therapy were performed. Patients received 25–150 mg AFQ056 or placebo twice-daily for 16 days (both studies). Study 2 included a four-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS; Study 1), the modified Abnormal Involuntary Movement Scale (mAIMS; Study 2), and the Unified PD Rating Scale–part III (UPDRS-III; both studies). Secondary outcomes included the UPDRS–part IV items 32–33. The primary analysis was change from baseline to Day 16 on all outcomes. Treatment differences were assessed. Results: Fifteen patients were randomized to AFQ056 and 16 to placebo in Study 1; 16 patients were randomized to each group in Study 2. AFQ056-treated patients showed significant improvements in dyskinesias at Day 16 versus placebo (e.g., LFADLDS, p = 0.021 [Study 1]; mAIMS, p = 0.032 [Study 2]). No significant changes were seen from baseline at Day 16 on the UPDRS-III in either study. Adverse events (AEs) were reported in both studies, including dizziness. Serious AEs (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by four AFQ056treated patients in Study 1, and three patients (two AFQ056-treated and one placebo group) in Study 2. Conclusions: AFQ056 showed a clinically relevant and significant anti-dyskinetic effect without changing the anti-parkinsonian effects of dopaminergic therapy. doi:10.1016/j.baga.2011.01.023
P104 Dopamine agonists and demented Parkinson’s disease patients: Really a no go? M.H. Strothjohann, G.A. Fuchs (Wolfach) Introduction: Dopamine agonists are known to cause more side effects than L-Dopa, as hallucinations, psychosis and states of delirium. Patients with Parkinson’s disease and dementia receive dopamine agonists rarely. Methods: We screened retrospectively 25 patients in our specialized Parkinson’ s disease Clinik Wolfach with parkinson’s disease (PD) and dementia (PDD), 21 men, 4 women, (mean age 75 years, range 61–85). Duration af disease mean 10 years (range 3–30 years). Reasons for treatment were bad motoric states with necessity to increase dopaminergic treatment. Results: The modifications of medical treatment of those patients revealed only one patient who tolerated no increase in dopaminergic treatment, 5 patients received dopaminergic treatment with an increase in L-Dopa alone, 7 patients received l_Dopa and COMTinhibition treatment. Surprisingly 11 patients did well with an combination of dopamine agonists, even 6 patients over 75 years. Conclusion: Even patients with PDD are able to benefit from a treatment with dopamine agonist, but it is recommended to do this in a hospital specialized in treatment of PD patients. Former studies are necessary to identify subgroups of PDD that will tolerate a dopamine agonist treatment and to select subgroups of well tolerated dopamine agonists. doi:10.1016/j.baga.2011.01.024
P105 Effect of rotigotine on sleep and nocturnal symptoms in Parkinson‘s Disease: Recover study C. Trenkwalder, E. Surmann, B. Boroojerdi on behalf of the Recover study group Background and aim: Few controlled studies have evaluated the treatment of sleep problems in PD as a primary outcome measure. This study aimed to assess the effects of 24-hour transdermal delivery of the non-ergoline dopamine receptor agonist, rotigotine, on sleep and nocturnal symptom outcomes in subjects with idiopathic Parkinson’s disease (PD). Methods: This was a multicenter, multinational, double-blind, placebo-controlled, parallel-group trial (NCT00474058) (presented at the XIV International Congress of Parkinson’s Disease and Movement Disorders (MDS); Buenos Aires, Argentina; June 2010; and partly presented at the XVIII WFN World Congress on Parkinson’s Disease and Related Disorders; Miami Beach, FL, USA; December 2009). Subjects with idiopathic PD and unsatisfactory early-morning motor control were randomized 2:1 to receive rotigotine (2–16 mg/24 h) (n = 190) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks and maintained at that dose for a further 4 weeks. Subjects were hospitalized for 2 nights before assessment at baseline and again at end of maintenance. The coprimary endpoint was the mean change in modified Parkinson’s Disease Sleep Scale (PDSS-2) total score from baseline to end of maintenance (Full Analysis Set, last observation carried forward). The PDSS-2 assesses sleep disturbance, early morning akinesia, and nocturnal motor and non-motor symptoms. Mean changes in PDSS-2 domain and individual item scores were additional exploratory endpoints. Treatment differences were estimated using an ANCOVA model. Results: Baseline mean (SD) PDSS-2 total scores were similar between treatment groups (placebo, 20.3 [10.2]; rotigotine, 19.3 [9.2]). The rotigotine group (n = 178) showed significantly greater
Abstract / Basal Ganglia 1 (2011) 13–45
bradykinesia, and fall) and the attrition rates due to these AEs. Other safety assessments include the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III; incidences of any AE and of serious AEs; pulmonary function tests (PEF and FEV1); Schellong test; and Epworth Sleepiness Scale. Efficacy assessments include Mattis Dementia Rating Scale (MDRS); Neuropsychiatric Inventory (NPI-10); Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL); and the MHYS. Results: Patient enrollment was closed in April 2009 after 583 patients had been randomized to treatment. Thirty-two percent were women. At screening, patients had a mean age (standard deviation, SD) of 72.4 (6.31) years and a mean MMSE score of 20.9 (3.36). Mean (SD) safety and efficacy scores were: UPDRS Part III 29.7 (11.89); MDRS 109.6 (19.09); NPI-10 11.3 (11.62); ADCS-ADL 49.5 (17.29). The modal stage of the MHYS was 3 shown by 235 (40.3%) patients. Conclusions: The study population is representative of patients with PDD. The study is expected to add to the long-term safety data on treatment of PDD with rivastigmine, in particular the effect of rivastigmine on the underlying motor symptoms of PD. doi:10.1016/j.baga.2011.01.022
P103 AFQ056 treatment of levodopa-induced dyskinesias: Results of two randomized controlled trials D. Berg, J. Godau, C. Trenkwalder, K. Eggert, I. Csoti, A. Storch, H. Huber, M. Morelli-Canelo, M. Stamelou, V. Ries, M. Wolz, C.B. Schneider, T. Di Paolo, F. Gasparini, S. Hariry, M. Vandemeulebroecke, W. Abi-Saab, K. Cooke, D. Johns, B. Gomez-Mancilla (Tübingen, Kassel, Marburg, Biskirchen, Dresden; Québec, CA; Basel, CH; High Wycombe, UK) Background: Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesias (LIDs). Methods: Two randomized, double-blind, placebo-controlled, parallel-group, inpatient studies for PD patients with moderate-to-severe (Study 1) and severe LIDs (Study 2) on stable dopaminergic therapy were performed. Patients received 25–150 mg AFQ056 or placebo twice-daily for 16 days (both studies). Study 2 included a four-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS; Study 1), the modified Abnormal Involuntary Movement Scale (mAIMS; Study 2), and the Unified PD Rating Scale–part III (UPDRS-III; both studies). Secondary outcomes included the UPDRS–part IV items 32–33. The primary analysis was change from baseline to Day 16 on all outcomes. Treatment differences were assessed. Results: Fifteen patients were randomized to AFQ056 and 16 to placebo in Study 1; 16 patients were randomized to each group in Study 2. AFQ056-treated patients showed significant improvements in dyskinesias at Day 16 versus placebo (e.g., LFADLDS, p = 0.021 [Study 1]; mAIMS, p = 0.032 [Study 2]). No significant changes were seen from baseline at Day 16 on the UPDRS-III in either study. Adverse events (AEs) were reported in both studies, including dizziness. Serious AEs (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by four AFQ056treated patients in Study 1, and three patients (two AFQ056-treated and one placebo group) in Study 2. Conclusions: AFQ056 showed a clinically relevant and significant anti-dyskinetic effect without changing the anti-parkinsonian effects of dopaminergic therapy. doi:10.1016/j.baga.2011.01.023
P104 Dopamine agonists and demented Parkinson’s disease patients: Really a no go? M.H. Strothjohann, G.A. Fuchs (Wolfach) Introduction: Dopamine agonists are known to cause more side effects than L-Dopa, as hallucinations, psychosis and states of delirium. Patients with Parkinson’s disease and dementia receive dopamine agonists rarely. Methods: We screened retrospectively 25 patients in our specialized Parkinson’ s disease Clinik Wolfach with parkinson’s disease (PD) and dementia (PDD), 21 men, 4 women, (mean age 75 years, range 61–85). Duration af disease mean 10 years (range 3–30 years). Reasons for treatment were bad motoric states with necessity to increase dopaminergic treatment. Results: The modifications of medical treatment of those patients revealed only one patient who tolerated no increase in dopaminergic treatment, 5 patients received dopaminergic treatment with an increase in L-Dopa alone, 7 patients received l_Dopa and COMTinhibition treatment. Surprisingly 11 patients did well with an combination of dopamine agonists, even 6 patients over 75 years. Conclusion: Even patients with PDD are able to benefit from a treatment with dopamine agonist, but it is recommended to do this in a hospital specialized in treatment of PD patients. Former studies are necessary to identify subgroups of PDD that will tolerate a dopamine agonist treatment and to select subgroups of well tolerated dopamine agonists. doi:10.1016/j.baga.2011.01.024
P105 Effect of rotigotine on sleep and nocturnal symptoms in Parkinson‘s Disease: Recover study C. Trenkwalder, E. Surmann, B. Boroojerdi on behalf of the Recover study group Background and aim: Few controlled studies have evaluated the treatment of sleep problems in PD as a primary outcome measure. This study aimed to assess the effects of 24-hour transdermal delivery of the non-ergoline dopamine receptor agonist, rotigotine, on sleep and nocturnal symptom outcomes in subjects with idiopathic Parkinson’s disease (PD). Methods: This was a multicenter, multinational, double-blind, placebo-controlled, parallel-group trial (NCT00474058) (presented at the XIV International Congress of Parkinson’s Disease and Movement Disorders (MDS); Buenos Aires, Argentina; June 2010; and partly presented at the XVIII WFN World Congress on Parkinson’s Disease and Related Disorders; Miami Beach, FL, USA; December 2009). Subjects with idiopathic PD and unsatisfactory early-morning motor control were randomized 2:1 to receive rotigotine (2–16 mg/24 h) (n = 190) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks and maintained at that dose for a further 4 weeks. Subjects were hospitalized for 2 nights before assessment at baseline and again at end of maintenance. The coprimary endpoint was the mean change in modified Parkinson’s Disease Sleep Scale (PDSS-2) total score from baseline to end of maintenance (Full Analysis Set, last observation carried forward). The PDSS-2 assesses sleep disturbance, early morning akinesia, and nocturnal motor and non-motor symptoms. Mean changes in PDSS-2 domain and individual item scores were additional exploratory endpoints. Treatment differences were estimated using an ANCOVA model. Results: Baseline mean (SD) PDSS-2 total scores were similar between treatment groups (placebo, 20.3 [10.2]; rotigotine, 19.3 [9.2]). The rotigotine group (n = 178) showed significantly greater