Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations

Rupam Borgohain, J. Szasz, P. Stanzione, C. Meshram, M. Bhatt, D. Chirilineau, F. Stocchi, V. Lucini, R. Giuliani, E. Forrest, P. Rice, R. Anand, M. Illiyas Sahadulla, U. Kardan, B. S. Keshava, A. Kishore, S. S. Kothari, J. M. Krishna Murthy, S. Kumar, P. Kumar Pal & 31 others N. Mehta, S. Prabhakar, S. Kr Prabhakar, S. Pradhan, A. K. Roy, C. Sankhla, P. K. Sethi, A. B. Shah, N. Shankar, R. Shukla, A. Sowani, R. Srinivasa, M. Varma, D. Vasudevan, P. Vavilikolanu Sreenivas, C. U. Velmurugendran, K. Vijayan, O. Bajenaru, A. Bulboaca, A. Campeanu, D. Chirileanu, D. Muresanu, C. Panea, C. Popescu, M. Simu, M. Ticmeanu, T. Avarello, U. Bonuccelli, R. Eleopra, M. Onofrj, R. Quatrale

Research output: Contribution to journalArticle

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Abstract

Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n=224), 50 mg/day (n=223), or placebo (n=222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean±SD increases in total on time with no or nontroublesome dyskinesia were 1.36±2.625 hours for safinamide 100 mg/day, 1.37±2.745 hours for safinamide 50 mg/day, and 0.97±2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.

Original languageEnglish
Pages (from-to)229-237
Number of pages9
JournalMovement Disorders
Volume29
Issue number2
DOIs
Publication statusPublished - 01-02-2014

Fingerprint

Levodopa
Parkinson Disease
Dyskinesias
Placebos
Dihydroxyphenylalanine
Parkinsonian Disorders
safinamide
Therapeutics
Least-Squares Analysis
Safety
Incidence

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Borgohain, R., Szasz, J., Stanzione, P., Meshram, C., Bhatt, M., Chirilineau, D., ... Quatrale, R. (2014). Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. Movement Disorders, 29(2), 229-237. https://doi.org/10.1002/mds.25751
Borgohain, Rupam ; Szasz, J. ; Stanzione, P. ; Meshram, C. ; Bhatt, M. ; Chirilineau, D. ; Stocchi, F. ; Lucini, V. ; Giuliani, R. ; Forrest, E. ; Rice, P. ; Anand, R. ; Illiyas Sahadulla, M. ; Kardan, U. ; Keshava, B. S. ; Kishore, A. ; Kothari, S. S. ; Krishna Murthy, J. M. ; Kumar, S. ; Kumar Pal, P. ; Mehta, N. ; Prabhakar, S. ; Prabhakar, S. Kr ; Pradhan, S. ; Roy, A. K. ; Sankhla, C. ; Sethi, P. K. ; Shah, A. B. ; Shankar, N. ; Shukla, R. ; Sowani, A. ; Srinivasa, R. ; Varma, M. ; Vasudevan, D. ; Vavilikolanu Sreenivas, P. ; Velmurugendran, C. U. ; Vijayan, K. ; Bajenaru, O. ; Bulboaca, A. ; Campeanu, A. ; Chirileanu, D. ; Muresanu, D. ; Panea, C. ; Popescu, C. ; Simu, M. ; Ticmeanu, M. ; Avarello, T. ; Bonuccelli, U. ; Eleopra, R. ; Onofrj, M. ; Quatrale, R. / Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. In: Movement Disorders. 2014 ; Vol. 29, No. 2. pp. 229-237.
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author = "Rupam Borgohain and J. Szasz and P. Stanzione and C. Meshram and M. Bhatt and D. Chirilineau and F. Stocchi and V. Lucini and R. Giuliani and E. Forrest and P. Rice and R. Anand and {Illiyas Sahadulla}, M. and U. Kardan and Keshava, {B. S.} and A. Kishore and Kothari, {S. S.} and {Krishna Murthy}, {J. M.} and S. Kumar and {Kumar Pal}, P. and N. Mehta and S. Prabhakar and Prabhakar, {S. Kr} and S. Pradhan and Roy, {A. K.} and C. Sankhla and Sethi, {P. K.} and Shah, {A. B.} and N. Shankar and R. Shukla and A. Sowani and R. Srinivasa and M. Varma and D. Vasudevan and {Vavilikolanu Sreenivas}, P. and Velmurugendran, {C. U.} and K. Vijayan and O. Bajenaru and A. Bulboaca and A. Campeanu and D. Chirileanu and D. Muresanu and C. Panea and C. Popescu and M. Simu and M. Ticmeanu and T. Avarello and U. Bonuccelli and R. Eleopra and M. Onofrj and R. Quatrale",
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Borgohain, R, Szasz, J, Stanzione, P, Meshram, C, Bhatt, M, Chirilineau, D, Stocchi, F, Lucini, V, Giuliani, R, Forrest, E, Rice, P, Anand, R, Illiyas Sahadulla, M, Kardan, U, Keshava, BS, Kishore, A, Kothari, SS, Krishna Murthy, JM, Kumar, S, Kumar Pal, P, Mehta, N, Prabhakar, S, Prabhakar, SK, Pradhan, S, Roy, AK, Sankhla, C, Sethi, PK, Shah, AB, Shankar, N, Shukla, R, Sowani, A, Srinivasa, R, Varma, M, Vasudevan, D, Vavilikolanu Sreenivas, P, Velmurugendran, CU, Vijayan, K, Bajenaru, O, Bulboaca, A, Campeanu, A, Chirileanu, D, Muresanu, D, Panea, C, Popescu, C, Simu, M, Ticmeanu, M, Avarello, T, Bonuccelli, U, Eleopra, R, Onofrj, M & Quatrale, R 2014, 'Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations', Movement Disorders, vol. 29, no. 2, pp. 229-237. https://doi.org/10.1002/mds.25751

Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. / Borgohain, Rupam; Szasz, J.; Stanzione, P.; Meshram, C.; Bhatt, M.; Chirilineau, D.; Stocchi, F.; Lucini, V.; Giuliani, R.; Forrest, E.; Rice, P.; Anand, R.; Illiyas Sahadulla, M.; Kardan, U.; Keshava, B. S.; Kishore, A.; Kothari, S. S.; Krishna Murthy, J. M.; Kumar, S.; Kumar Pal, P.; Mehta, N.; Prabhakar, S.; Prabhakar, S. Kr; Pradhan, S.; Roy, A. K.; Sankhla, C.; Sethi, P. K.; Shah, A. B.; Shankar, N.; Shukla, R.; Sowani, A.; Srinivasa, R.; Varma, M.; Vasudevan, D.; Vavilikolanu Sreenivas, P.; Velmurugendran, C. U.; Vijayan, K.; Bajenaru, O.; Bulboaca, A.; Campeanu, A.; Chirileanu, D.; Muresanu, D.; Panea, C.; Popescu, C.; Simu, M.; Ticmeanu, M.; Avarello, T.; Bonuccelli, U.; Eleopra, R.; Onofrj, M.; Quatrale, R.

In: Movement Disorders, Vol. 29, No. 2, 01.02.2014, p. 229-237.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations

AU - Borgohain, Rupam

AU - Szasz, J.

AU - Stanzione, P.

AU - Meshram, C.

AU - Bhatt, M.

AU - Chirilineau, D.

AU - Stocchi, F.

AU - Lucini, V.

AU - Giuliani, R.

AU - Forrest, E.

AU - Rice, P.

AU - Anand, R.

AU - Illiyas Sahadulla, M.

AU - Kardan, U.

AU - Keshava, B. S.

AU - Kishore, A.

AU - Kothari, S. S.

AU - Krishna Murthy, J. M.

AU - Kumar, S.

AU - Kumar Pal, P.

AU - Mehta, N.

AU - Prabhakar, S.

AU - Prabhakar, S. Kr

AU - Pradhan, S.

AU - Roy, A. K.

AU - Sankhla, C.

AU - Sethi, P. K.

AU - Shah, A. B.

AU - Shankar, N.

AU - Shukla, R.

AU - Sowani, A.

AU - Srinivasa, R.

AU - Varma, M.

AU - Vasudevan, D.

AU - Vavilikolanu Sreenivas, P.

AU - Velmurugendran, C. U.

AU - Vijayan, K.

AU - Bajenaru, O.

AU - Bulboaca, A.

AU - Campeanu, A.

AU - Chirileanu, D.

AU - Muresanu, D.

AU - Panea, C.

AU - Popescu, C.

AU - Simu, M.

AU - Ticmeanu, M.

AU - Avarello, T.

AU - Bonuccelli, U.

AU - Eleopra, R.

AU - Onofrj, M.

AU - Quatrale, R.

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n=224), 50 mg/day (n=223), or placebo (n=222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean±SD increases in total on time with no or nontroublesome dyskinesia were 1.36±2.625 hours for safinamide 100 mg/day, 1.37±2.745 hours for safinamide 50 mg/day, and 0.97±2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.

AB - Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n=224), 50 mg/day (n=223), or placebo (n=222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean±SD increases in total on time with no or nontroublesome dyskinesia were 1.36±2.625 hours for safinamide 100 mg/day, 1.37±2.745 hours for safinamide 50 mg/day, and 0.97±2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.

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Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt M, Chirilineau D et al. Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. Movement Disorders. 2014 Feb 1;29(2):229-237. https://doi.org/10.1002/mds.25751