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Updated long-term safety from ongoing phase 3 trials of levodopa-carbidopa intestinal gel in patients with advanced Parkinson's disease
Abstracts / Parkinsonism and Related Disorders 22 (2016) e87ee141
supportive of the overall tolerability of LCIG.
Table 1 Adverse Event Summary as of 31 March 2014 cut-off.
Table 1 Gastrointestinal Adverse Drug Reactions Over the First Six Months of LCIG Treatment. Post-PEG-J Placement Weeks Number of Patients Out of 343a 1-2 Any ADR 43 Any Serious ADR 17 ADRs occurring in 5 patients Any Procedure-related 14 Postoperative wound infection 3 Any Device-related 17 Device related infection 10 Device dislocation 2 Device lead issue 2 Any Other Type of GI Event 17 Weight decreased 5 Abdominal pain 6 Serious ADRs occurring in 2 patients Any Procedure-related 9 Pneumoperitoneum 3 Postoperative wound infection 2 Procedural complication 2 Any Device-related 4 Device dislocation 1 Any Other Type of GI Event 6 Abdominal pain 2
e97
Months 3-4 6 3
2 7 3
3 11 4
4 14 2
5 5 1
6 5 0
1-6b 70 27
1 0 4 0 2 1 1 1 0
0 0 4 0 3 0 3 2 0
1 0 8 0 3 0 2 0 0
3 2 5 0 0 0 7 5 0
1 0 2 0 0 1 2 0 1
1 1 3 1 0 1 1 0 0
18 5 39 11 9 5 31 13 7
0 0 0 0 3 2 0 0
0 0 0 0 2 2 1 0
0 0 0 0 3 2 1 0
0 0 0 0 1 0 1 0
0 0 0 0 0 0 1 1
0 0 0 0 0 0 0 0
9 3 2 2 12 6 10 3
a 266 patients (78%) completed at least 6 months of LCIG treatment post-PEG-J placement. b Incidence of initial event during months 1-6, therefore this column is not a sum of the other columns.
P 2.068. UPDATED LONG-TERM SAFETY FROM ONGOING PHASE 3 TRIALS OF LEVODOPA-CARBIDOPA INTESTINAL GEL IN PATIENTS WITH ADVANCED PARKINSON'S DISEASE Ramon Rodriguez 1, Nathan Schmulewitz 2, David Stein 3, Weining Robieson 4, Coleen Hall 4, Susan Eaton 4, Krai Chatamra 4, Janet Benesh 4, Alberto Espay 2. 1 University of Florida College of Medicine, Gainesville, United States; 2 University of Cincinnati, Cincinnati, United States; 3 Quintiles, San Diego, United States; 4 AbbVie Inc., North Chicago, United States Objectives: To summarize the integrated long-term safety data of levodopa-carbidopa intestinal gel (LCIG/carbidopa-levodopa enteral suspension [CLES]) from four ongoing phase 3 studies through 31 March 2014. Methods: Cumulative data from all patients receiving open-label LCIG treatment (N¼412), were used to present all safety except that related to the device/procedure (D/P). Data from all patients with PEG-J placement (N¼395), were used to evaluate safety associated with the D/P Results: Exposure to LCIG at cutoff averaged 854 (SD¼564) days. 94% (387) of patients had a treatment-emergent AE of any kind (Table 1). Over the 963 total patient years of exposure, 18% (72) discontinued participation due to an AE, most commonly: complication of device insertion (2.4%), death (1.2%), abdominal pain (1.0%), and pneumonia (1.0%). There were 34 deaths (8.3%) due to an AE: 2 were considered possibly related to the treatment system and 32 unrelated or unlikely related. Conclusions: The majority of the D/P-associated AEs are known complications of PEG-J; most of the non-D/P associated AEs are frequently associated with levodopa, PD, or elderly. Discontinuation due to AE was low compared to PD trials of much shorter duration.1 This cumulative update of the largest, longest-term safety dataset for LCIG should be considered when evaluating benefit/risk associated with this treatment. References: 1. Stocchi et al. Mov. Disord. 2013;38:1838-1846. 2. Pahwa et al. Park. Rel. Disord. 2014;20:142-148.
Device/Procedure-Associated (Total patients¼395)
Non-Device/Procedure-Associated (Total patients¼412)
Adverse event (AE)a
n patients (%) Adverse event (AE)a
Any D/P AE Any serious D/P AE Most common AEs: Complication of device insertion Abdominal painb Procedural pain Postoperative wound infection
300 (76%) 68 (17%)
n patients (%)
160 (41%)
Any non-D/P AE 379 (92%) Any serious non-D/P AE 171 (42%) Most common AEs: Insomnia 96 (23%)
142 (36%) 107 (27%) 104 (26%)
Fall Constipation Nausea
95 (23%) 84 (20%) 84 (20%)
a
A single event could be coded to >1 preferred term. Events with this term were most often additionally coded to abdominal pain, abdominal discomfort, abdominal distension, flatulence, pneumoperitoneum. b
P 2.069. ITALIAN SURVEY ON INTRADUODENAL LEVODOPA GEL TREATMENT IN ADVANCED PARKINSON DISEASE: STATE OF THE ART 10 YEARS AFTER MARKETING Mariachiara Sensi 1, Giovanni Cossu 2, Francesca Mancini 3, Nicola Modugno 4, Manuela Pilleri 5, Rocco Quatrale 6, Filippo Tamma 7, Maurizio Zibetti 8, Marco Aguggia 9, Angelo Antonini 10, Luigi Bartolomei 32, Marianna Amboni 12, Daniela Calandrella 13, Margherita Canesi 14, Maria Gabriella Ceravolo 15, Roberto Ceravolo 16, Pietro Cortelli 17, Roberto Eleopra 18, Enrico Grassi 19, Marco Guido 20, Graziano Mario Coletti 22, Pietro Marano 23, Francesca Gusmaroli 21, Morgante 24, Claudio Pacchetti 25, Giulio Riboldazzi 26, Simone Alessandro Stefani 28, Giuseppe Meco 29, Alessandro Rossi 27, Tessitore 30, Giovanni Fabbrini 31, Maria Valeria Saddi 32. 1 Department of Neuroscience, Ferrara, Italy; 2 Department of Neurology, OSP-Brotzu, Cagliari, Italy; 3 Department of Neurology, San Pio X-Milano, Milan, Italy; 4 Department of Neurology, Neuromed IRCSS Pozzilli, Pozzilli, Italy; 5 Department of Neurology, Casa di Cura Villa Margherita, Vicenza, Italy; 6 Department of Neurology, Ospedale dell’Angelo, Mestre, Italy; 7 Department of Neurology, Miuli, Acquaviva delle Fonti (BA), Italy; 8 della Salute e della Scienza di Torino, Department of Neuroscience, Citta Turin, Italy; 9 Reparto/Servizio: SOC Neurologia e Stroke Unit, Asti, Italy; 10 Department of Neurology, IRCCS San Camillo, Lido di Venezia, Italy; 12 Neurologia, ICD Hermitage-Capodimonte, Napoli, Italy; 13 Department of Neurology, Istituto Besta, Milan, Italy; 14 Centro Parkinson, ICP Milano, Milan, Italy; 15 Centro Diagnosi e Cura Disturbi del Movimento, Clinica di Neuroriabilitazione, Dipartimento di Scienze Neurologiche, Ancona, Italy; 16 Department of Neurology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy; 17 Department of Neurology, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 18 Department of Neurology, Azienda Ospedaliero Universitaria S.Maria della Misericordia, Udine, Italy; 19 Department of Neurology, Ospedale S.Stefano, Prato, Italy; 20 Department of Neurology, Centro per la Diagnosi e Cura dei Disturbi del Movimento, Policlinico di Bari, Bari, Italy; 21 Department of Neurology, Ospedale degli Infermi, Biella, Italy; 22 Department of Neurology, Servizio Neurologia, Ospedale Mauriziano Umberto I, Turin, Italy; 23 Department of Neuroriabilitation, Casa di Cura Carmide, Villa dei Gerani, Catania, Italy; 24 Department of Neurology, UOSD Neurofisiopatologia e Disordini del Movimento, AOU G. Martino, Messina, Italy; 25 Department of Neurology, Istituto Neurologico Nazionale, IRCCS, C. Mondino, Pavia, Italy; 26 Department of Neurology, Ospedale di Circolo e Fondazione Macchi, Varese, Italy; 27 Department of Neurology, Dipartimento di Neuroscienze, AOUS Siena, Italy; 28 Department of Neurology, Fondazione Policlinico Tor Vergata, Roma, Italy; 29 di Roma La Department of Neurology, Centro Parkinson, Universita Sapienza, Policlinico Umberto I, Rome, Rome, Italy; 30 Department of Neurology, I Clinica Neurologica, I Policlinico di Napoli (SUN), Naples, Italy; 31 di Roma La Sapienza, Policlinico Department of Neurology, Universita Umberto I, Rome, Italy; 32 Departement of Neurology-Osp.Nuoro, Nuoro, Italy Objectives: Levodopa/carbidopa intestinal gel infusion (LCIG, Duodopa) is
supportive of the overall tolerability of LCIG.
Table 1 Adverse Event Summary as of 31 March 2014 cut-off.
Table 1 Gastrointestinal Adverse Drug Reactions Over the First Six Months of LCIG Treatment. Post-PEG-J Placement Weeks Number of Patients Out of 343a 1-2 Any ADR 43 Any Serious ADR 17 ADRs occurring in 5 patients Any Procedure-related 14 Postoperative wound infection 3 Any Device-related 17 Device related infection 10 Device dislocation 2 Device lead issue 2 Any Other Type of GI Event 17 Weight decreased 5 Abdominal pain 6 Serious ADRs occurring in 2 patients Any Procedure-related 9 Pneumoperitoneum 3 Postoperative wound infection 2 Procedural complication 2 Any Device-related 4 Device dislocation 1 Any Other Type of GI Event 6 Abdominal pain 2
e97
Months 3-4 6 3
2 7 3
3 11 4
4 14 2
5 5 1
6 5 0
1-6b 70 27
1 0 4 0 2 1 1 1 0
0 0 4 0 3 0 3 2 0
1 0 8 0 3 0 2 0 0
3 2 5 0 0 0 7 5 0
1 0 2 0 0 1 2 0 1
1 1 3 1 0 1 1 0 0
18 5 39 11 9 5 31 13 7
0 0 0 0 3 2 0 0
0 0 0 0 2 2 1 0
0 0 0 0 3 2 1 0
0 0 0 0 1 0 1 0
0 0 0 0 0 0 1 1
0 0 0 0 0 0 0 0
9 3 2 2 12 6 10 3
a 266 patients (78%) completed at least 6 months of LCIG treatment post-PEG-J placement. b Incidence of initial event during months 1-6, therefore this column is not a sum of the other columns.
P 2.068. UPDATED LONG-TERM SAFETY FROM ONGOING PHASE 3 TRIALS OF LEVODOPA-CARBIDOPA INTESTINAL GEL IN PATIENTS WITH ADVANCED PARKINSON'S DISEASE Ramon Rodriguez 1, Nathan Schmulewitz 2, David Stein 3, Weining Robieson 4, Coleen Hall 4, Susan Eaton 4, Krai Chatamra 4, Janet Benesh 4, Alberto Espay 2. 1 University of Florida College of Medicine, Gainesville, United States; 2 University of Cincinnati, Cincinnati, United States; 3 Quintiles, San Diego, United States; 4 AbbVie Inc., North Chicago, United States Objectives: To summarize the integrated long-term safety data of levodopa-carbidopa intestinal gel (LCIG/carbidopa-levodopa enteral suspension [CLES]) from four ongoing phase 3 studies through 31 March 2014. Methods: Cumulative data from all patients receiving open-label LCIG treatment (N¼412), were used to present all safety except that related to the device/procedure (D/P). Data from all patients with PEG-J placement (N¼395), were used to evaluate safety associated with the D/P Results: Exposure to LCIG at cutoff averaged 854 (SD¼564) days. 94% (387) of patients had a treatment-emergent AE of any kind (Table 1). Over the 963 total patient years of exposure, 18% (72) discontinued participation due to an AE, most commonly: complication of device insertion (2.4%), death (1.2%), abdominal pain (1.0%), and pneumonia (1.0%). There were 34 deaths (8.3%) due to an AE: 2 were considered possibly related to the treatment system and 32 unrelated or unlikely related. Conclusions: The majority of the D/P-associated AEs are known complications of PEG-J; most of the non-D/P associated AEs are frequently associated with levodopa, PD, or elderly. Discontinuation due to AE was low compared to PD trials of much shorter duration.1 This cumulative update of the largest, longest-term safety dataset for LCIG should be considered when evaluating benefit/risk associated with this treatment. References: 1. Stocchi et al. Mov. Disord. 2013;38:1838-1846. 2. Pahwa et al. Park. Rel. Disord. 2014;20:142-148.
Device/Procedure-Associated (Total patients¼395)
Non-Device/Procedure-Associated (Total patients¼412)
Adverse event (AE)a
n patients (%) Adverse event (AE)a
Any D/P AE Any serious D/P AE Most common AEs: Complication of device insertion Abdominal painb Procedural pain Postoperative wound infection
300 (76%) 68 (17%)
n patients (%)
160 (41%)
Any non-D/P AE 379 (92%) Any serious non-D/P AE 171 (42%) Most common AEs: Insomnia 96 (23%)
142 (36%) 107 (27%) 104 (26%)
Fall Constipation Nausea
95 (23%) 84 (20%) 84 (20%)
a
A single event could be coded to >1 preferred term. Events with this term were most often additionally coded to abdominal pain, abdominal discomfort, abdominal distension, flatulence, pneumoperitoneum. b
P 2.069. ITALIAN SURVEY ON INTRADUODENAL LEVODOPA GEL TREATMENT IN ADVANCED PARKINSON DISEASE: STATE OF THE ART 10 YEARS AFTER MARKETING Mariachiara Sensi 1, Giovanni Cossu 2, Francesca Mancini 3, Nicola Modugno 4, Manuela Pilleri 5, Rocco Quatrale 6, Filippo Tamma 7, Maurizio Zibetti 8, Marco Aguggia 9, Angelo Antonini 10, Luigi Bartolomei 32, Marianna Amboni 12, Daniela Calandrella 13, Margherita Canesi 14, Maria Gabriella Ceravolo 15, Roberto Ceravolo 16, Pietro Cortelli 17, Roberto Eleopra 18, Enrico Grassi 19, Marco Guido 20, Graziano Mario Coletti 22, Pietro Marano 23, Francesca Gusmaroli 21, Morgante 24, Claudio Pacchetti 25, Giulio Riboldazzi 26, Simone Alessandro Stefani 28, Giuseppe Meco 29, Alessandro Rossi 27, Tessitore 30, Giovanni Fabbrini 31, Maria Valeria Saddi 32. 1 Department of Neuroscience, Ferrara, Italy; 2 Department of Neurology, OSP-Brotzu, Cagliari, Italy; 3 Department of Neurology, San Pio X-Milano, Milan, Italy; 4 Department of Neurology, Neuromed IRCSS Pozzilli, Pozzilli, Italy; 5 Department of Neurology, Casa di Cura Villa Margherita, Vicenza, Italy; 6 Department of Neurology, Ospedale dell’Angelo, Mestre, Italy; 7 Department of Neurology, Miuli, Acquaviva delle Fonti (BA), Italy; 8 della Salute e della Scienza di Torino, Department of Neuroscience, Citta Turin, Italy; 9 Reparto/Servizio: SOC Neurologia e Stroke Unit, Asti, Italy; 10 Department of Neurology, IRCCS San Camillo, Lido di Venezia, Italy; 12 Neurologia, ICD Hermitage-Capodimonte, Napoli, Italy; 13 Department of Neurology, Istituto Besta, Milan, Italy; 14 Centro Parkinson, ICP Milano, Milan, Italy; 15 Centro Diagnosi e Cura Disturbi del Movimento, Clinica di Neuroriabilitazione, Dipartimento di Scienze Neurologiche, Ancona, Italy; 16 Department of Neurology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy; 17 Department of Neurology, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 18 Department of Neurology, Azienda Ospedaliero Universitaria S.Maria della Misericordia, Udine, Italy; 19 Department of Neurology, Ospedale S.Stefano, Prato, Italy; 20 Department of Neurology, Centro per la Diagnosi e Cura dei Disturbi del Movimento, Policlinico di Bari, Bari, Italy; 21 Department of Neurology, Ospedale degli Infermi, Biella, Italy; 22 Department of Neurology, Servizio Neurologia, Ospedale Mauriziano Umberto I, Turin, Italy; 23 Department of Neuroriabilitation, Casa di Cura Carmide, Villa dei Gerani, Catania, Italy; 24 Department of Neurology, UOSD Neurofisiopatologia e Disordini del Movimento, AOU G. Martino, Messina, Italy; 25 Department of Neurology, Istituto Neurologico Nazionale, IRCCS, C. Mondino, Pavia, Italy; 26 Department of Neurology, Ospedale di Circolo e Fondazione Macchi, Varese, Italy; 27 Department of Neurology, Dipartimento di Neuroscienze, AOUS Siena, Italy; 28 Department of Neurology, Fondazione Policlinico Tor Vergata, Roma, Italy; 29 di Roma La Department of Neurology, Centro Parkinson, Universita Sapienza, Policlinico Umberto I, Rome, Rome, Italy; 30 Department of Neurology, I Clinica Neurologica, I Policlinico di Napoli (SUN), Naples, Italy; 31 di Roma La Sapienza, Policlinico Department of Neurology, Universita Umberto I, Rome, Italy; 32 Departement of Neurology-Osp.Nuoro, Nuoro, Italy Objectives: Levodopa/carbidopa intestinal gel infusion (LCIG, Duodopa) is