The XINDI Study: A Randomized Phase III Clinical Trial Evaluating the Efficacy and Safety of Safinamide as Add-On Therapy to Levodopa in Chinese Patients with Parkinson’s Disease with Motor Fluctuations

Wei, Qianqian; Tan, Yuyan; Cattaneo, C; Chen, Shengdi; Shang, Huifang; Tao, Enxiang; Liu, Chunfeng; Wu, Yuncheng; Geng, Deqin; Lu, Zuneng; Xu, Pingyi; Hu, Xingyue; Luo, Yan; Zhou, Jie; Huang, Wei; Chen, Guoqian; Tian, Yuling; Tuo, Houzhen; Wang, Qianqian; Zhang, Meiyun; Liu, Junyan; Sun, Xin; Jiao, Lei; Jin, Lingjing; Feng, Tao; Liu, Yiming; Zhang, Baorong; Ye, Qinyong; Xu, Yong; Liu, Jian-Ren; Gu, Shaojuan; Xu, Yan; Dong, Xueshuang; Liú, Dan; Pan, Xiaoping

doi:10.1007/s40263-022-00958-6

Cited by 16 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Japanese "ME2125-3 " study confirmed significant benefits of safinamide vs. placebo after 24 weeks in PD patients with wearing-off on levodopa treatment, regarding daily ON time (+ 1.4 h at 50 mg, + 1.7 h at 100 mg) and additional measures including daily OFF time, and the UPDRS subscores for parts I, II, and III (Hattori et al 2020). Recently, data of the Chinese phase III, double-blind, placebo-controlled, pivotal XINDI trial have been published which confirmed a positive effect of safinamide on motor fluctuations and motor symptoms (Wei et al 2022).…”

Section: Safinamidementioning

confidence: 99%

Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations

Regensburger

Kohl

et al. 2023

J Neural Transm

View full text Add to dashboard Cite

Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong its effect in striatal dopaminergic neurotransmission in Parkinson’s disease patients. While selegiline/rasagiline and tolcapone/entacapone have been available on the market for more than one decade, safinamide and opicapone have been approved in 2015 and 2016, respectively. Meanwhile, comprehensive data from several post-authorization studies have described the use and specific characteristics of the individual substances in clinical practice under real-life conditions. Here, we summarize current knowledge on both medication classes, with a focus on the added clinical value in Parkinson’s disease. Furthermore, we outline practical considerations in the treatment of motor fluctuations and provide an outlook on ongoing studies with MAO-B and COMT inhibitors.

show abstract

Section: Safinamidementioning

confidence: 99%

Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations

Regensburger

Kohl

et al. 2023

J Neural Transm

View full text Add to dashboard Cite

show abstract

“…The efficacy of safinamide in reducing motor fluctuations and improving motor symptoms and quality of life has also been demonstrated in a phase III randomized, double‐blind, placebo‐controlled trial conducted in Chinese patients with idiopathic PD orally administered 100 mg of safinamide once daily for 16 weeks as add‐on therapy to L‐dopa 27 . The safety of the study treatment was good and comparable to that observed in the previous studies.…”

mentioning

confidence: 93%

Pharmacokinetic and Safety Study of Single and Multiple Oral Doses of Safinamide in Healthy Chinese Volunteers

Sun

Yuan

Leuratti³

et al. 2023

Clinical Pharm in Drug Dev

Self Cite

View full text Add to dashboard Cite

This randomized, parallel‐group study evaluated the plasma pharmacokinetic profile of safinamide in 24 healthy Chinese men and women, randomly assigned to receive 50 or 100 mg of safinamide as a single dose, followed, after a 7‐day washout, by multiple doses once daily for 7 days. Plasma safinamide was determined up to 96 h after the first single dose (day 1) and the last multiple dose (day 14), and up to 24 h after the first multiple dose (day 8). Following single‐ and multiple‐dose administration, peak concentrations were achieved at a median time of 1.5–2 h. Plasma exposure increased in a dose‐proportional manner. After single dose, mean half‐life was 23–24 h. Area under the concentration‐time curve (AUC) from time zero extrapolated to infinity was only slightly higher than AUC from time zero to the last quantifiable concentration, corresponding for the 2 parameters, respectively, to 12,380 and 11,560 ng • h/mL for the 50 mg and to 22,030 and 20,790 ng • h/mL for the 100‐mg dose. AUC in the dosing interval at steady state was 13,150 and 23,100 ng • h/mL for 50 and 100 mg of safinamide. Steady state was reached in 6 days, accumulation was approximately twofold, and the pharmacokinetics were time independent. The plasma safinamide pharmacokinetic profile observed in this study is in line with the published results in both Chinese and non‐Asian populations.

show abstract

“…Safinamide is a monoamine oxidase B inhibitor that is unique for its reversible monoamine oxidase B inhibition and voltage-dependent sodium channel blockade effect ( 15 ), and its efficacy in reducing wearing-off has been demonstrated by three Phase III trials and a Phase II/III trial ( 16 – 19 ). In these trials, 57.7% to 64.3% of subjects showed a clinical response to 24-week treatment with safinamide 100 mg/day, as defined either by a 1-h or greater increase in ON-time without troublesome dyskinesia or by Clinical Global Impression — Change.…”

Section: Introductionmentioning

confidence: 99%

Sustained response in early responders to safinamide in patients with Parkinson's disease and motor fluctuations: A post hoc analysis of the SETTLE study

et al. 2023

View full text Add to dashboard Cite

Safinamide is a selective, reversible, monoamine oxidase B inhibitor for the treatment of patients with Parkinson's disease (PD) and motor fluctuations. This was a post hoc analysis of the SETTLE study, in which patients with PD and motor fluctuations were randomly assigned to 24-week treatment with safinamide (50 mg/day for 2 weeks, increased to 100 mg/day if tolerated) or placebo. In the present analysis, responders were defined according to their treatment responses at Week 2 and Week 24 based on changes in ON-time without troublesome dyskinesia from baseline with cutoffs of 1 hour. It was found that 81% (103/127) of the responders at Week 2 maintained the response through Week 24 in the safinamide group. Other outcomes did not necessarily coincide with the ON-time response; however, “Early” responders who showed a treatment response at both Week 2 and Week 24 had substantial improvements from baseline in OFF-time, UPDRS Part II and III scores, and PDQ-39 summary index scores through Week 24. The safinamide group had a higher proportion of early responders than the placebo group (39% vs 20%, p < 0.0001). At baseline, early responders in the safinamide group had significantly higher UPDRS Part II and III scores, shorter ON-time, and longer OFF-time than the other responder populations. In conclusion, the results of the present post hoc analysis suggest that patients with a short ON-time, severe motor symptoms, and highly compromised activities of daily living can benefit from safinamide early in treatment and over the long term.

show abstract

The XINDI Study: A Randomized Phase III Clinical Trial Evaluating the Efficacy and Safety of Safinamide as Add-On Therapy to Levodopa in Chinese Patients with Parkinson’s Disease with Motor Fluctuations

Cited by 16 publications

References 37 publications

Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations

Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations

Pharmacokinetic and Safety Study of Single and Multiple Oral Doses of Safinamide in Healthy Chinese Volunteers

Sustained response in early responders to safinamide in patients with Parkinson's disease and motor fluctuations: A post hoc analysis of the SETTLE study

Contact Info

Product

Resources

About