When used as an add-on treatment to carbidopa-levodopa, Nourianz (istradefylline) reduced the duration of “off periods” — when symptoms are not adequately controlled — and increased the duration of “on periods” in Parkinson’s disease patients with and without pre-existing dyskinesia, a pooled analysis of several clinical trials has found.
The findings, “Impact of Baseline Dyskinesia on the Safety and Efficacy of Istradefylline, an Adenosine A2A Receptor Antagonist, in Patients with Parkinson’s Disease: a Pooled Analysis of 8 Clinical Studies,” were presented at the 6th Congress of the European Academy of Neurology (EAN), which took place virtually May 23–26.
Carbidopa-levodopa is one of the mainstay treatments used to alleviate the symptoms of Parkinson’s. The combination therapy works by increasing the levels of dopamine, which is a brain chemical essential for balance and movement coordination whose levels are very low in patients with Parkinson’s.
However, over time and as the disease progresses, treatment may become less effective at preventing symptoms. When that happens, many patients start experiencing so-called “off episodes,” or periods of time when treatment is no longer effective at keeping disease symptoms at bay.
Nourianz, marketed by Kyowa Hakko Kirin Pharma, is an add-on treatment approved by the U.S. Food and Drug Administration (FDA) to treat off episodes in patients receiving carbidopa-levodopa. Involuntary muscle movement, also known as dyskinesia, is the most common side effect of Nourianz.
Investigators at Kyowa now have presented the findings of a pooled analysis of several clinical trials they conducted to evaluate the possible impact of pre-existing dyskinesia (baseline dyskinesia) on the safety and effectiveness of Nourianz.
The analysis was based on data from eight randomized, placebo-controlled trials involving 2,719 patients with Parkinson’s who experienced off episodes while taking levodopa/carbidopa.
During the trials, patients were assigned randomly to receive either Nourianz at a daily dose of 20 mg, or 40 mg, or a placebo, for a period of 12 or 16 weeks.
The analysis included those with baseline dyskinesia, as well as those who did not have dyskinesia before adding Nourianz or a placebo to their treatment regimen.
Data revealed that compared to placebo, Nourianz reduced the duration of off periods and increased the duration of on periods without troublesome dyskinesia, as reported by patients.
This was true for patients with and without baseline dyskinesia, suggesting that pre-existing dyskinesia did not compromise Nourianz’s overall effectiveness.
A post hoc subanalysis also found that troublesome dyskinesia was reported more frequently by patients with baseline dyskinesia, regardless of whether they were being treated with Nourianz or a placebo, compared to those who did not have pre-existing dyskinesia.
“The results being presented at EAN suggest that dyskinesia is observed more often in patients with baseline dyskinesia before [Nourianz] was added to the treatment regimen and that the overall efficacy of [Nourianz] was not affected by patients’ baseline status,” Stuart Isaacson, MD, said in a press release. Issacson is a neurologist at the Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida.
“We believe these data can be helpful to physicians as they make treatment decisions and may provide insight into the appropriate use of Nourianz in the treatment of ‘OFF’ time in patients with PD [Parkinson’s disease],” Isaacson said.