Two-Year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease

Study 018 Investigators

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P50.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression.

Original languageEnglish
Pages (from-to)1273-1280
Number of pages8
JournalMovement Disorders
Volume29
Issue number10
DOIs
Publication statusPublished - 01-01-2014

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Dyskinesias
Levodopa
Parkinson Disease
Placebos
Quality of Life
Depression
Activities of Daily Living
safinamide
Motor Activity

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

@article{1b2bef4900404a1e9a2273e9e49d58ac,
title = "Two-Year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease",
abstract = "In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36{\%} of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P50.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression.",
author = "{Study 018 Investigators} and Rupam Borgohain and Jozsef Szasz and Paolo Stanzione and Chandrashekhar Meshram and Bhatt, {Mohit H.} and Dana Chirilineau and Fabrizio Stocchi and Valentina Lucini and Rodolfo Giuliani and Emma Forrest and Patricia Rice and Ravi 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 J. Szasz and M. Ticmeanu and T. Avarello and U. Bonuccelli and R. Eleopra",
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language = "English",
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Two-Year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease. / Study 018 Investigators.

In: Movement Disorders, Vol. 29, No. 10, 01.01.2014, p. 1273-1280.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Two-Year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease

AU - Study 018 Investigators

AU - Borgohain, Rupam

AU - Szasz, Jozsef

AU - Stanzione, Paolo

AU - Meshram, Chandrashekhar

AU - Bhatt, Mohit H.

AU - Chirilineau, Dana

AU - Stocchi, Fabrizio

AU - Lucini, Valentina

AU - Giuliani, Rodolfo

AU - Forrest, Emma

AU - Rice, Patricia

AU - Anand, Ravi

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 - Szasz, J.

AU - Ticmeanu, M.

AU - Avarello, T.

AU - Bonuccelli, U.

AU - Eleopra, R.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P50.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression.

AB - In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P50.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression.

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JF - Movement Disorders

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