Safinamide a safe and miraculous add-on therapy to Levodopa in Parkinson's disease
A new trial from China revealed that Safinamide has significantly reduced motor fluctuations, improved motor symptoms, and also the quality of life in patients with idiopathic Parkinson's disease. It had good tolerability and was found to be clinically safe as per the trial results that were published in the journal CNS Drugs.
Parkinson's disease is a progressive neurodegenerative disorder. The gold standard treatment is Levodopa, but long-term usage of levodopa has motor complications and is quite challenging to treat. Recent literature shows that Safinamide's dual mechanism of action offers a unique approach to managing motor complications as an adjunct to levodopa. Hence researchers conducted a trial to investigate the efficacy and safety of safinamide as an add-on to levodopa in Chinese patients with Parkinson's disease with motor fluctuations.
The XINDI study was a phase III, multicenter, randomized, double-blind, placebo-controlled trial with a 2-week screening and 16-week treatment period. The starting dose of safinamide (or placebo) was 50 mg once daily, increased to 100 mg once daily on day 15. Patients should follow a stable oral levodopa regimen and may receive concomitant treatment with stable doses of other anti-Parkinson drugs, except monoamine oxidase-B inhibitors.
| Inclusion Criteria | |
| Age - ≥ 18 years, | |
Have idiopathic Parkinson's disease of >3 years duration, | |
Hoehn and Yahr stage 1–4, | |
daily OFF time ≥ 1.5 h. | |
| Exclusion criteria | |
severe disabling peak-dose or biphasic dyskinesia, | |
unpredictable or widely swinging fluctuations, | |
other forms of parkinsonism, | |
a history of dementia or severe cognitive dysfunction, | |
major psychiatric illnesses, | |
and/or clinically significant medical illnesses. |
Any change from baseline to week 16 in the mean daily OFF time was considered the primary efficacy endpoint. Secondary efficacy endpoints included the Unified Parkinson's Disease Rating Scale, the Numerical Rating Scale, the Clinical Global Impression scale, and the 39-Item Parkinson's Disease Questionnaire scale.
Analysis of covariance was used for the statistical analysis of the efficacy parameters, except for the Clinical Global Impression scale scores that were assessed using the Wilcoxon–Mann–Whitney test. Safety was evaluated through the frequency of adverse events and serious adverse events, physical examination, vital signs, 12-lead electrocardiograms, and laboratory exams. Descriptive statistics were used to summarize all the safety endpoints.
Results:
- 307 patients were enrolled.
- The difference in the change of the mean total daily OFF time at week 16, between the safinamide and placebo groups, was 1.10 h (p < 0.0001).
- This change was significantly greater in the safinamide group starting from week 2, suggesting a rapid onset of drug efficacy.
- Statistically significant improvements were seen in the ON time, Unified Parkinson's Disease Rating Scale, Clinical Global Impression scale, and the 39-Item Parkinson's Disease Questionnaire.
- There were no significant between-group differences for adverse events or serious adverse events.
Thus, Safinamide worked as a safe, tolerable, and good add-on therapy to levodopa by significantly reducing motor fluctuations and improving motor symptoms and quality of life of Chinese patients with idiopathic Parkinson's disease.
Further reading: Wei, Q., Tan, Y., Xu, P. et al. 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. CNS Drugs 36, 1217–1227 (2022). https://doi.org/10.1007/s40263-022-00958-6
