Xadago Shows Potential in Small Study to Ease Urinary Problems

Xadago (safinamide) — approved as an add-on therapy to ease “off periods” that can accompany levodopa — may also help with urinary symptoms in people with Parkinson’s disease, a small study reports.

These early findings support previous studies showing that Xadago may be addressing Parkinson’s non-motor symptoms.

Larger studies are needed to confirm these results, the researchers noted.

The study, “SURINPARK: Safinamide for Urinary Symptoms in Parkinson’s Disease,” was published in the journal Brain Sciences.

While motor problems are the hallmark of Parkinson’s, patients often experience non-motor symptoms, including those of the urinary tract.

Urinary symptoms, such as nocturia (excessive urination at night), increased urinary frequency and urgency, and incontinence, are estimated to affect one-quarter to nearly all Parkinson’s patients. They negatively weigh on daily activities, quality of sleep, and are a source of social stigma, ultimately affecting patients’ quality of life.

Given the likely multifactorial nature of urinary symptoms in Parkinson’s, their treatment remains challenging.

Xadago is an oral, once a day add-on therapy to levodopa in Parkinson’s patients experiencing “off” episodes — the reappearance or worsening of motor symptoms before a new levodopa dose can be taken.

Levodopa, the mainstay treatment of Parkinson’s, is a precursor of dopamine, the brain signaling molecule (neurotransmitter) gradually lost in Parkinson’s, leading to motor problems.

Developed by Newron Pharmaceuticals and marketed by Zambon, Xadago raises dopamine levels by blocking the activity of both the enzyme that normally breaks down dopamine, and the transporters responsible for its absorption and retention. At higher doses (100 mg), the therapy was also shown to suppress the excessive release of glutamate, another neurotransmitter.

Notably, previous studies suggested that Xadago may lessen Parkinson’s non-motor symptoms, such as pain and mood fluctuations. However, its effects on urinary symptoms remain unclear.

A team of researchers at Hospital Universitario Ramon y Cajal, in Madrid, set out to assess whether Xadago would have a beneficial effect on urinary problems in Parkinson’s patients.

They retrospectively analyzed the clinical data of 114 patients followed at the Movement Disorder Unit of their hospital: 35 treated with 100 mg of Xadago as an add-on levodopa therapy, and 79 given other treatment options.

Patients had no history of previous treatment with Xadago, and no cognitive difficulties or severe urinary incontinence or retention. Urinary symptoms were assessed through the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms-urinary (SCOPA-AUT-U) at a routine visit, and then through a telephone call at least one month later (after at least one month of Xadago treatment among the group using it).

At first assessment, clinical and demographic features were similar between both treatment groups, and urinary problems common to both. However, patients given Xadago as an adjunct therapy showed a trend toward longer disease duration, more advanced disease, and significantly higher SCOPA-AUT-U scores — meaning more severe urinary symptoms.

During follow-up, three Xadago group patients discontinued the treatment due to adverse events (mild to moderate confusion and drowsiness), and one patient in the other group left the study, leaving 110 people for the final analysis.

Results showed that patients treated with Xadago had a significant, 27% drop in SCOPA-AUT-U total scores, mainly driven by reductions in the scale’s frequency, nocturia, urgency, and incontinence domains.

Notably, the number of nocturia episodes dropped by 56% in these patients after one month of treatment, which “probably had a more global functional improvement in these patients through sleep quality improvement,” the researchers wrote.

No significant changes in urinary symptoms were found between the two assessments among patients on treatments other than Xadago.

These findings suggest “a possible benefit of the addition of [Xadago] 100 mg to [patients’ treatment] regimes, with overall good tolerability and consistent [lessening] of the different [urinary] symptoms, especially the irritative and nocturnal,” the team wrote.

While the underlying mechanisms of Xadago’s benefits on urinary problems remain unknown, the researchers hypothesized that they are likely associated with its non-dopaminergic effects.

Future, controlled studies are needed to clarify these findings, the researchers noted.

This study’s publication was sponsored by Zambon, but the company had no role in the collection, analysis, and interpretation of the data, according to its authors.