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Pooled safety and tolerability of opicapone in the treatment of Parkinson’s disease and motor fluctuations
Abstracts / Parkinsonism and Related Disorders 22 (2016) e87ee141
Lisbon, Portugal; 2 National Hospital for Neurology and Neurosurgery, London, United Kingdom; 3 BIAL, Portela & Cª S.A., S. Mamede Coronado, Portugal
Disord. 2013;28:131-144. Table 1 DELTA G. Delta G Kcal/Mol 1-Methylxathine Caffeine Theophylline Theobromine Adenosine
e101
-7.50 -7.65 -7.88 -7.57 -7.92
Ă
P 2.079. META-ANALYSIS: DONEPEZIL IN THE TREATMENT OF COGNITIVE IMPAIRMENT & DEMENTIA IN PATIENTS WITH PARKINSON’S DISEASE Ela Barcelon, Leah Shiong Shu, Paul Matthew Pasco. Department of Neurosciences, Philippine General Hospital, Manila, Philippines Objective: Evaluate the efficacy and safety of Donepezil in improving cognitive function of patients with Parkinson’s Disease diagnosed to have Cognitive Impairment or Dementia. Methods: Meta-analysis of randomized controlled trials comparing Donepezil versus placebo in the management of Parkinson’s Disease patients with cognitive impairment or dementia. Mean differences were computed using RevMan Version 5.1. Results: Fifty-five studies were screened for inclusion in this meta-analysis. Only four studies met the inclusion and exclusion criteria. Administration of Donepezil 10mg/tab for at least 4 weeks showed statistically significant improvement in the cognitive function of Parkinson’s Disease patients with dementia or cognitive impairment in terms of MMSE. There were no significant differences in the other scales measured. Incidence of adverse events was found to be higher in the Donepezil group, but this was not statistically significant. Conclusions: This study successfully demonstrated the efficacy of Donepezil in cognitively impaired Parkinson’s Disease patient in the improvement of MMSE without significant impact on motor symptoms. References: Van Den Eeden S, et al., 2003; Hughes TA, et al., 2000; Aarsland D, et al., 2001; Marder K, et al., 1995; Marttila RJ and Rinne UK, 1976; Lieberman A, et al., 1979; Boller F, et al., 1980; Brown RG and Marsden CD, 1984, Yoshimura, 1988; Friedman A and Barcikowska M., 1994; Aarsland D, Brønnick K, Fladby T., 2011; Leroi I, et al. 2012; Fernandez et al. 2005; Dubois B and Pillon B, 1997; Nakano I and Hirano A, 1984. P 2.080. POOLED EFFICACY OF OPICAPONE AS ADJUNCTIVE THERAPY TO LEVODOPA IN PATIENTS WITH PARKINSON’S DISEASE AND MOTOR FLUCTUATIONS Joaquim Ferreira 1, Andrew Lees 2, Nelson Lopes 3, Ana Santos 3, JoseFrancisco Rocha 3, Patricio Soares-da-Silva 3. 1 Laboratory of Clinical Pharmacology and Therapeutics Faculty of Medicine, University of Lisbon,
Objectives: Evaluate the efficacy of opicapone (OPC) in patients with Parkinson’s disease (PD) and motor fluctuations across phase III studies. Methods: Patient-level data of matching treatment arms of BIPARK I and II studies was integrated (placebo, 25mg-OPC and 50mg-OPC). Both were multicentre, 14 to 15-week double-blind, randomised, placebo- and active-(only BIPARK I)-controlled studies and had similar designs and measurement instruments. The primary efficacy variable was the change from baseline in absolute OFF-time based on patient’s diaries. Key secondary measure was the OFF-time responder rates ( 1 hour). Results: The pooled efficacy set included 758 subjects (placebo n¼255, 25mg-OPC n¼241, 50mg-OPC n¼262). Treatment with either OPC 25mg or 50mg significantly reduced daily OFF-time (-37.4 min and -64.4 min vs. placebo; p<0.05 and p<0.0001, respectively) and increased the ON-time without troublesome dyskinesia (42.7 min and 64.7 min vs. placebo; p<0.05 and p<0.0001, respectively). Significantly more patients receiving either OPC 25 mg (61.4%, p<0.05) or 50 mg (67.6%, p<0.0001) achieved the 1hour OFF-time responder endpoint compared to placebo (49.0%). Similar results were observed for ONtime responders. Conclusions: OPC is effective in reducing OFF-time and increasing ONtime without troublesome dyskinesia. P 2.081. POOLED SAFETY AND TOLERABILITY OF OPICAPONE IN THE TREATMENT OF PARKINSON’S DISEASE AND MOTOR FLUCTUATIONS Joaquim Ferreira 2, Helena Gama 3, Cristina Andrew Lees 1, Oliveira 3, Nelson Lopes 3, Jose-Francisco Rocha 3, Patricio Soares-daSilva 3. 1 National Hospital for Neurology and Neurosurgery, London, United Kingdom; 2 Laboratory of Clinical Pharmacology and Therapeutics Faculty of Medicine, University of Lisbon, Lisbon, Portugal; 3 BIAL, Portela & Cª S.A., S. Mamede Coronado, Portugal Objectives: Evaluate the safety of opicapone (OPC) in patients with Parkinson’s disease (PD) and motor fluctuations across phase III studies. Methods: Patient-level data of matching treatment arms of BIPARK I and II studies was integrated (placebo, 25mg-OPC and 50mg-OPC). Both were multicentre, 14 to 15-week double-blind, randomised, placebo- and active(only BIPARK I)-controlled studies and had similar designs and measurement instruments. Safety was assessed by incidence of treatment-emergent adverse events (TEAEs), changes in laboratory values, ECGs and vital signs. Results: The pooled safety set included 766 patients (N¼257, 244 and 265 for placebo, 25mg- and 50mg-OPC). Dopaminergic events and other PD symptoms were the most commonly reported TEAEs: dyskinesia (18.3% OPC vs. 6.2% placebo), constipation (5.7% vs. 1.9%), insomnia (5.1% vs. 1.6%) and dry mouth (4.7% vs. 1.2%). No dose relationship was observed for the majority of TEAEs. Serious AEs were reported for few patients: 4.3% placebo and 3.5% OPC. One death (pneumonia) occurred in the placebo group. There were no reports of severe diarrhea, myocardial infarction, prostate cancer, melanoma or any serious hepatic event in OPC groups. Impulse control disorders were reported by <1% of OPC-treated patients. No relevant differences compared to placebo were observed for laboratory parameters, vital signs or ECG readings. Conclusions: OPC is safe and well tolerated with no apparent association to known safety concerns of other anti-PD drugs, particularly other COMT inhibitors. P 2.082. PANDA: PROLONGED RELEASE OXYCODONE/NALOXONE (OXN PR) FOR SEVERE PARKINSON’S DISEASE (PD)-RELATED PAIN K. Ray Chaudhuri 1, Pablo Martinez-Martin 2, Olivier Rascol 3, Mark Lomax 4, Julia DeCesare 4, Michael Hopp 5. 1 King’s College Hospital, London, United Kingdom; 2 National Centre of Epidemiology, Carlos III
Lisbon, Portugal; 2 National Hospital for Neurology and Neurosurgery, London, United Kingdom; 3 BIAL, Portela & Cª S.A., S. Mamede Coronado, Portugal
Disord. 2013;28:131-144. Table 1 DELTA G. Delta G Kcal/Mol 1-Methylxathine Caffeine Theophylline Theobromine Adenosine
e101
-7.50 -7.65 -7.88 -7.57 -7.92
Ă
P 2.079. META-ANALYSIS: DONEPEZIL IN THE TREATMENT OF COGNITIVE IMPAIRMENT & DEMENTIA IN PATIENTS WITH PARKINSON’S DISEASE Ela Barcelon, Leah Shiong Shu, Paul Matthew Pasco. Department of Neurosciences, Philippine General Hospital, Manila, Philippines Objective: Evaluate the efficacy and safety of Donepezil in improving cognitive function of patients with Parkinson’s Disease diagnosed to have Cognitive Impairment or Dementia. Methods: Meta-analysis of randomized controlled trials comparing Donepezil versus placebo in the management of Parkinson’s Disease patients with cognitive impairment or dementia. Mean differences were computed using RevMan Version 5.1. Results: Fifty-five studies were screened for inclusion in this meta-analysis. Only four studies met the inclusion and exclusion criteria. Administration of Donepezil 10mg/tab for at least 4 weeks showed statistically significant improvement in the cognitive function of Parkinson’s Disease patients with dementia or cognitive impairment in terms of MMSE. There were no significant differences in the other scales measured. Incidence of adverse events was found to be higher in the Donepezil group, but this was not statistically significant. Conclusions: This study successfully demonstrated the efficacy of Donepezil in cognitively impaired Parkinson’s Disease patient in the improvement of MMSE without significant impact on motor symptoms. References: Van Den Eeden S, et al., 2003; Hughes TA, et al., 2000; Aarsland D, et al., 2001; Marder K, et al., 1995; Marttila RJ and Rinne UK, 1976; Lieberman A, et al., 1979; Boller F, et al., 1980; Brown RG and Marsden CD, 1984, Yoshimura, 1988; Friedman A and Barcikowska M., 1994; Aarsland D, Brønnick K, Fladby T., 2011; Leroi I, et al. 2012; Fernandez et al. 2005; Dubois B and Pillon B, 1997; Nakano I and Hirano A, 1984. P 2.080. POOLED EFFICACY OF OPICAPONE AS ADJUNCTIVE THERAPY TO LEVODOPA IN PATIENTS WITH PARKINSON’S DISEASE AND MOTOR FLUCTUATIONS Joaquim Ferreira 1, Andrew Lees 2, Nelson Lopes 3, Ana Santos 3, JoseFrancisco Rocha 3, Patricio Soares-da-Silva 3. 1 Laboratory of Clinical Pharmacology and Therapeutics Faculty of Medicine, University of Lisbon,
Objectives: Evaluate the efficacy of opicapone (OPC) in patients with Parkinson’s disease (PD) and motor fluctuations across phase III studies. Methods: Patient-level data of matching treatment arms of BIPARK I and II studies was integrated (placebo, 25mg-OPC and 50mg-OPC). Both were multicentre, 14 to 15-week double-blind, randomised, placebo- and active-(only BIPARK I)-controlled studies and had similar designs and measurement instruments. The primary efficacy variable was the change from baseline in absolute OFF-time based on patient’s diaries. Key secondary measure was the OFF-time responder rates ( 1 hour). Results: The pooled efficacy set included 758 subjects (placebo n¼255, 25mg-OPC n¼241, 50mg-OPC n¼262). Treatment with either OPC 25mg or 50mg significantly reduced daily OFF-time (-37.4 min and -64.4 min vs. placebo; p<0.05 and p<0.0001, respectively) and increased the ON-time without troublesome dyskinesia (42.7 min and 64.7 min vs. placebo; p<0.05 and p<0.0001, respectively). Significantly more patients receiving either OPC 25 mg (61.4%, p<0.05) or 50 mg (67.6%, p<0.0001) achieved the 1hour OFF-time responder endpoint compared to placebo (49.0%). Similar results were observed for ONtime responders. Conclusions: OPC is effective in reducing OFF-time and increasing ONtime without troublesome dyskinesia. P 2.081. POOLED SAFETY AND TOLERABILITY OF OPICAPONE IN THE TREATMENT OF PARKINSON’S DISEASE AND MOTOR FLUCTUATIONS Joaquim Ferreira 2, Helena Gama 3, Cristina Andrew Lees 1, Oliveira 3, Nelson Lopes 3, Jose-Francisco Rocha 3, Patricio Soares-daSilva 3. 1 National Hospital for Neurology and Neurosurgery, London, United Kingdom; 2 Laboratory of Clinical Pharmacology and Therapeutics Faculty of Medicine, University of Lisbon, Lisbon, Portugal; 3 BIAL, Portela & Cª S.A., S. Mamede Coronado, Portugal Objectives: Evaluate the safety of opicapone (OPC) in patients with Parkinson’s disease (PD) and motor fluctuations across phase III studies. Methods: Patient-level data of matching treatment arms of BIPARK I and II studies was integrated (placebo, 25mg-OPC and 50mg-OPC). Both were multicentre, 14 to 15-week double-blind, randomised, placebo- and active(only BIPARK I)-controlled studies and had similar designs and measurement instruments. Safety was assessed by incidence of treatment-emergent adverse events (TEAEs), changes in laboratory values, ECGs and vital signs. Results: The pooled safety set included 766 patients (N¼257, 244 and 265 for placebo, 25mg- and 50mg-OPC). Dopaminergic events and other PD symptoms were the most commonly reported TEAEs: dyskinesia (18.3% OPC vs. 6.2% placebo), constipation (5.7% vs. 1.9%), insomnia (5.1% vs. 1.6%) and dry mouth (4.7% vs. 1.2%). No dose relationship was observed for the majority of TEAEs. Serious AEs were reported for few patients: 4.3% placebo and 3.5% OPC. One death (pneumonia) occurred in the placebo group. There were no reports of severe diarrhea, myocardial infarction, prostate cancer, melanoma or any serious hepatic event in OPC groups. Impulse control disorders were reported by <1% of OPC-treated patients. No relevant differences compared to placebo were observed for laboratory parameters, vital signs or ECG readings. Conclusions: OPC is safe and well tolerated with no apparent association to known safety concerns of other anti-PD drugs, particularly other COMT inhibitors. P 2.082. PANDA: PROLONGED RELEASE OXYCODONE/NALOXONE (OXN PR) FOR SEVERE PARKINSON’S DISEASE (PD)-RELATED PAIN K. Ray Chaudhuri 1, Pablo Martinez-Martin 2, Olivier Rascol 3, Mark Lomax 4, Julia DeCesare 4, Michael Hopp 5. 1 King’s College Hospital, London, United Kingdom; 2 National Centre of Epidemiology, Carlos III