Long-term Efficacy of Safinamide on Parkinson's Disease Chronic Pain.
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ABSTRACT:
SUBMITTER: Cattaneo C
PROVIDER: S-EPMC5910467 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundParkinson's disease (PD) is characterized by a wide range of motor and non-motor symptoms. Levodopa is still the most effective drug; however, its long-term use is associated with motor complications which may deteriorate patient's quality of life. Safinamide is a unique treatment modulating both dopaminergic and glutamatergic systems. Previous results from two six months, double-blind, placebo-controlled studies demonstrated that safinamide has positive effects on both motor functions and quality of life in PD patients.ObjectiveTo investigate the effects of safinamide 100 mg/day over two-year treatment on PD symptoms severity and quality of life, using data from the study 018.MethodsData from 352 patients were analyzed to evaluate the effects of safinamide on OFF time and ON time (with no or non-troublesome dyskinesia) in the overall population and in subgroups of patients (receiving levodopa monotherapy or with other anti-Parkinson therapies), and the effects of safinamide on motor symptoms/clinical fluctuations (by means of UPDRS III and IV) and on health-related quality of life (using UPDRS II and PDQ-39 summary index score).ResultsSafinamide, administered as add-on to standard therapy in fluctuating PD patients, significantly improved motor symptoms and clinical fluctuations in the overall population and in some subgroups of patients. Additionally, safinamide improved quality of life and activities of daily living, maintaining the efficacy in the long-term.ConclusionsThe findings of these analyses suggest that safinamide may be considered an appropriate adjunct therapy in patient not sufficiently controlled. Further investigations are desirable to confirm these results in usual care setting.
| S-EPMC7029312 | biostudies-literature
Project description:Safinamide is a novel ?-aminoamide with dopaminergic and non-dopaminergic properties developed as adjunctive therapy for patients with PD. Results from a 24-month double-blind controlled study suggested that as add-on to levodopa (and other PD medications) the benefits of safinamide on dyskinesia may be related to severity of dyskinesia at baseline.This post-hoc analysis further characterized the effects of safinamide on dyskinesia in mid- to late-stage PD patients.Patients were stratified by the presence or absence of dyskinesia at baseline, and by whether or not the dose of levodopa had been changed during the 24-month treatment period. Differences between safinamide and placebo were evaluated using the Wilcoxon rank-sum test.For the overall treated population (with or without baseline dyskinesia), safinamide 100?mg/day significantly improved the dyskinesia rating scale score, compared with placebo, in the subgroup of patients with no change in levodopa dose (p?=?0.0488). For patients with baseline dyskinesia, improvements over placebo were also significant (p?=?0.0153) in patients with or without changes in levodopa dose, and nearly significant (p?=?0.0546) in patients with no change in levodopa dose, suggesting that these improvements were not due to levodopa dose reductions.While no statistically significant difference in mean DRS scores was seen between safinamide and placebo in the original study population, the present post-hoc analysis helps to provide a meaningful interpretation of the long-term effects of safinamide on dyskinesia. These results may be related to safinamide state- and use-dependent inhibition of sodium channels and stimulated glutamate release, and are unlikely due to reduced dopaminergic stimulation.
| S-EPMC4923744 | biostudies-literature
Project description:Background and objectivePain is a frequent and disabling symptom in Parkinson's disease (PD) patients. Our aim was to analyze the effectiveness of safinamide on pain in PD patients from the SAFINONMOTOR (an open-label study of the effectiveness of SAFInamide on NON-MOTOR symptoms in Parkinson´s disease patients) study.Material and methodsSAFINONMOTOR is a prospective open-label single-arm study conducted in five centers from Spain. In this analysis, a secondary objective of the study, the score in the KPPS (King´s Parkinson´s Disease Pain Scale) at V1 (baseline) and V4 (6 months ± 1 month) were compared. Wilcoxon´s rank sum test was performed to test the changes from V1 to V4.ResultsForty-four (88%) out of 50 PD patients (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis) completed the study. The KPPS total score was reduced by 43.6% (from 40.04 ± 36.18 in V1 to 22.60 ± 21.42 in V4; p < 0.0001). By domains, improvement was observed in musculoskeletal (-35.9%; p = 0.009), fluctuation-related (-51.7%; p = 0.020), nocturnal (-46.1%; p = 0.001), discoloration and/or edema/swelling (-50.4%; p = 0.009) and radicular pain (-40.1%; p = 0.048). A total of 21 adverse events in 11 patients (22%) were reported, five being severe, but not related to safinamide.ConclusionSafinamide is well tolerated and improves pain in PD patients at 6 months. Future studies are necessary to analyze the possible beneficial effect of safinamide on pain in PD patients.
| S-EPMC8402181 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of safinamide administration compared to placebo in PD patients on multiple outcomes.MethodsPubMed, EMBASE, Cochrane CENTRAL, LILACS, and trial databases were searched up to 23 December 2020 for randomized controlled studies (RCTs) comparing safinamide to placebo, alone or as add-on therapy in PD. Data were extracted from literature and regulatory agencies. Primary outcomes were ON-time without troublesome dyskinesia, OFF-time, and Unified Parkinson's Disease Rating Scale (UPDRS) section III (UPDRS-III). Secondary outcomes included any dyskinesia rating scale (DRS), ON-time with troublesome dyskinesia, UPDRS-II, and Parkinson's Disease Questionnaire 39 (PDQ-39). In order to estimate mean difference (MD) and odds ratios with 95% confidence intervals (CI), generic inverse variance and Mantel-Haenszel methods were used for continuous and dichotomous variables, respectively. Analyses were performed grouping by PD with (PDwMF) or without (PDwoMF) motor fluctuations, safinamide dose, and concomitant dopaminergic treatment. Summary of findings with GRADE were performed.ResultsSix studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa (L-dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = - 1.06 h; 95% CI from - 1.60 to - 0.51), and improved UPDRS-III (MD = - 2.77; 95% CI from - 4.27 to - 1.28) with moderate quality of evidence. Similar results were observed for the 50 mg dose. However, the quality of evidence was moderate only for ON-time without troublesome dyskinesia, whereas for OFF-time and UPDRS-III was low. In PDwoMF patients taking a single dopamine agonist, safinamide 100 mg resulted in little to no clinically significant improvement in UPDRS-III (MD = - 1.84; 95% CI from - 3.19 to - 0.49), with moderate quality of evidence. Conversely, in PDwoMF patients, the 200 mg and 50 mg doses showed nonsignificant improvement in UPDRS-III, with very low and moderate quality of evidence, respectively. In PDwMF patients taking safinamide 100 mg or 50 mg, nonsignificant differences were observed for ON-time with troublesome dyskinesia and DRS, with high and low quality of evidence, respectively. In the same patients, UPDRS-II was significantly improved at the 100 mg and 50 mg dose, with high and moderate quality of evidence. In PDwoMF, UPDRS-II showed a little yet significant difference only at 100 mg, with low quality of evidence. PDQ-39 resulted significantly improved only with the 100 mg dose in PDwMF, with low quality of evidence.ConclusionOverall, safinamide is effective in PDwMF patients taking L-dopa both at 100 and 50 mg daily. Evidence for efficacy in early PD is limited. Further trials are needed to better evaluate the anti-dyskinetic properties of safinamide.
| S-EPMC8004480 | biostudies-literature
Project description:This post-hoc analysis investigated the long-term effects of safinamide on the course of dyskinesia and efficacy outcomes using data from a phase III, open-label 52-week study of safinamide 50 or 100 mg/day in Japanese patients with Parkinson's disease (PD) with wearing-off. Patients (N = 194) were grouped using the UPDRS Part IV item 32: with and without pre-existing dyskinesia (pre-D subgroup; item 32 > 0 at baseline [n = 81], without pre-D subgroup; item 32 = 0 at baseline [n = 113]). ON-time with troublesome dyskinesia (ON-TD) increased significantly from baseline to Week 4 in the pre-D subgroup (+ 0.25 ± 0.11 h [mean ± SE], p = 0.0355) but gradually decreased up to Week 52 (change from baseline: - 0.08 ± 0.17 h, p = 0.6224); ON-TD did not change significantly in the Without pre-D subgroup. UPDRS Part IV item 32 score increased significantly at Week 52 compared with baseline in the Without pre-D subgroup, but no UPDRS Part IV dyskinesia related-domains changed in the pre-D subgroup. Both subgroups improved in ON-time without TD, UPDRS Part III, and Part II [OFF-phase] scores. The cumulative incidence of new or worsening dyskinesia (adverse drug reaction) at Week 52 was 32.5 and 5.0% in the pre-D and Without pre-D subgroups, respectively. This study suggested that safinamide led to short-term increasing dyskinesia but may be not associated with marked dyskinesia at 1-year follow-up in patients with pre-existing dyskinesia, and that it improved motor symptoms regardless of the presence or absence of dyskinesia at baseline. Further studies are warranted to investigate this association in more details.Trial registration: JapicCTI-153057 (Registered: 2015/11/02).
| S-EPMC9468087 | biostudies-literature
Project description:Safinamide is an orally administered α-aminoamide derivative with both dopaminergic and non-dopaminergic properties. Nonlinear mixed effects models for population pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PKPD) analyses were developed using records from, respectively, 623 and 668 patients belonging to two Phase 3, randomized, placebo-controlled, double-blind efficacy studies. The aim was to estimate safinamide population PK parameters in patients with Parkinson's disease (PD) on stable levodopa therapy, and to develop a model of safinamide effect on the PD phase of normal functioning (ON-time). The final models were internally evaluated using visual predictive checks (VPCs), prediction corrected-VPC, and nonparametric bootstrap analysis. Safinamide profiles were adequately described by a linear one-compartmental model with first-order absorption and elimination. CL/F, Vd/F, and KA (95% confidence interval [CI]) were 4.96 (4.73-5.21) L/h, 166 (158-174) L, and 0.582 (0.335-0.829) h-1, respectively. CL/F and Vd/F increased with body weight, while age, gender, renal function, and exposure to levodopa did not influence safinamide PK. The observed ON-time values were adequately described by a linear model, with time in the study period as dependent variable, and rate of ON-time change and baseline plus offset effect as slope and intercept parameters. Safinamide treatment resulted in an increase in ON-time of 0.73 h (week 4), with further ON-time increase with the same slope as placebo. The increase was not influenced by age, levodopa, or safinamide exposure. The population models adequately describe the population PK of safinamide and safinamide effect on ON-time. No dose adjustments in elderly and mild to moderate renally impaired patients are requested.
| S-EPMC5045937 | biostudies-literature
Project description:Background: Safinamide, a recently developed drug with several mechanisms of action has been investigated as an add-on therapy for Parkinson's disease patients suffering from motor complications due to the usage of anti-Parkinson's medications such as levodopa and dopaminergic drugs. The aim of the study is to investigate the efficacy and safety of Safinamide as add-on therapy for Parkinson's disease patients. Methods: A computerized literature search was conducted of PubMed, EMBASE, ClinicalTrial.gov and Cochrane Library until August 2019. We selected relevant randomized controlled trials comparing safinamide groups to placebo groups. Relevant outcomes were pooled as mean difference (MD) and risk ratio (RR) using Review Manager 5.3. Results: We found that the overall MD of changes in "off-time" and "on time without troublesome dyskinesia" favored the safinamide group over the placebo group (MD -0.72 h, 95% CI -0.89 to -0.56 and MD 0.71 h, 95% CI 0.52 to 0.90, respectively). Additionally, the overall MD of change in Unified Parkinson's Disease Rating Scale part three (UPDRS III) favored the safinamide group (MD -1.83, 95% CI -2.43 to -1.23). In case of adverse events, the pooled meta-analysis did not favor the safinamide group over the placebo group. Conclusions: In this study, we provide class I evidence about the potential role of safinamide as an add-on therapy for Parkinson's disease patients suffering from motor fluctuations. However, a few included studies did not mention the data of important outcomes. Also, we report high risk of bias in individual studies. Future randomized controlled trials with different doses are recommended to provide more evidence for the efficacy and safety of safinamide as a treatment for motor complications of anti-Parkinson's medications.
| S-EPMC7205357 | biostudies-literature
Project description:ObjectivesOne in 5 people in the United States lives with chronic pain. Many patients with chronic pain experience a subset of specific co-occurring pain conditions that may share a common pain mechanism and that have been designated as chronic overlapping pain conditions (COPCs). Little is known about chronic opioid prescribing patterns among patients with COPCs in primary care settings, especially among socioeconomically vulnerable patients. This study aims to evaluate opioid prescribing among patients with COPCs in US community health centers and to identify individual COPCs and their combinations that are associated with long-term opioid treatment (LOT).Study designRetrospective cohort study.MethodsWe conducted analyses of more than 1 million patients 18 years and older based on electronic health record data from 449 US community health centers across 17 states between January 1, 2009, and December 31, 2018. Logistic regression models were used to assess the relationship between COPCs and LOT.ResultsIndividuals with COPCs were prescribed LOT 4 times more often than individuals without a COPC (16.9% vs 4.0%). The presence of chronic low back pain, migraine headache, fibromyalgia, or irritable bowel syndrome combined with any of the other COPCs increased the odds of LOT prescribing compared with the presence of a single COPC.ConclusionsAlthough LOT prescribing has declined over time, it remains relatively high among patients with certain COPCs and for those with multiple COPCs. These study findings suggest target populations for future interventions to manage chronic pain among socioeconomically vulnerable patients.
| S-EPMC10516299 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:To assess the long-term safety and efficacy of pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). METHODS:In two double-blind (DB) studies of early PD and one of advanced PD,active-treatment arms received pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375-4.5 mg q.d.). RESULTS:Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ?10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ?10.0%were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) PartsII + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to pramipexole introduction, at -6.6 and -6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of pramipexole (33 DB plus 80 OL) in early PD, and -11.5 and -9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. CONCLUSIONS:These results support the long-term safety and efficacy of pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.
| S-EPMC4282380 | biostudies-literature
Project description:Rasagiline is a monoamine oxidase type-B inhibitor in development in Japan for Parkinson's disease (PD). This open-label study evaluated the long-term safety and efficacy of rasagiline in Japanese patients with PD receiving levodopa. Patients were aged 30-79 years and had wearing-off or weakened effect. Patients received rasagiline 1 mg/day for 52 weeks. The primary objective was to evaluate safety. Secondary endpoints included MDS-UPDRS Part II and Part III total scores (ON-state) and change from baseline in mean daily OFF-time. An additional endpoint was the Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index (SI) score. In total, 222 patients were enrolled; 52.3% had wearing-off phenomena. Treatment-emergent adverse events (TEAEs) were mostly mild or moderate and occurred in 83.3% of patients; 63.1% had drug-related TEAEs; and 21.2% had TEAEs resulting in discontinuation. Fall (16.7%), nasopharyngitis (14.0%), and dyskinesia (10.8%) were the most frequent TEAEs. Serious TEAEs were reported in 17.6% of patients, and led to discontinuation in 9.5%. At week 52 (last-observation-carried forward), the mean change from baseline in MDS-UPDRS Part III total score (ON-state) was - 7.6; the mean change from baseline in daily OFF-time was - 0.89 h in patients with wearing-off phenomena at the start of the run-in period. The mean change from baseline in PDQ-39 SI was - 0.64. No major safety issues were observed during this 52-week trial of rasagiline as an adjunct to levodopa in Japanese patients. Mean changes in MDS-UPDRS scores and daily OFF-time suggested that adjunctive rasagiline treatment with levodopa was efficacious, with efficacy maintained for at least 52 weeks.
| S-EPMC6449487 | biostudies-literature