January 10, 2020
By Reuters Staff
NEW YORK (Reuters Health) - Apomorphine sublingual film significantly reduces off episodes in patients with Parkinson's disease, according to results of a phase 3 study.
As many as 90% of patients with Parkinson's disease receiving chronic levodopa treatment develop motor fluctuations and dyskinesias. Subcutaneous apomorphine is approved for the on-demand management of off episodes in these patients, but the need for a subcutaneous injection and initial titration supervised in clinic, potentially severe dopaminergic side effects, and the frequent development of skin nodules and ulcerations at injection sites have limited its acceptance.
Dr. C. Warren Olanow from Icahn School of Medicine at Mount Sinai, New York and colleagues from 33 centers investigated the safety and efficacy of a novel apomorphine sublingual film as on-demand therapy for off episodes. The randomized, double-blind, placebo-controlled study involved 141 patients with Parkinson's disease (including 109 who entered the double-blind phase of the study).
The mean change from predose to 30 minutes postdose in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3 score at the 12-week visit, the primary endpoint, was significantly greater in the apomorphine sublingual film group (an 11.1-point improvement) than in the placebo group (a 3.5-point improvement), the researchers reported in Lancet Neurology.
Similarly, the percentage of patients with a self-rated full on response within 30 minutes at the 12-week visit, the key secondary endpoint, was significantly greater with apomorphine sublingual film (35%) than with placebo (16%).
During the titration phase of the study, 12 patients (9%) discontinued the study as a result of adverse events, and during the double-blind maintenance phase, an additional 15 patients (28%) discontinued apomorphine sublingual film treatment as a result of adverse events.
Most discontinuations of apomorphine sublingual film were associated with oropharyngeal adverse events (9 patients, 17%). Only one patient treated with placebo discontinued treatment as a result of oropharyngeal adverse events.
"Although nearly a third of patients discontinued treatment primarily because of oropharyngeal side effects, apomorphine sublingual film provided an efficacious, on-demand treatment for off episodes for most patients with Parkinson's disease in this trial," the authors conclude. "The long-term safety and efficacy of apomorphine sublingual film are currently being investigated."
"The availability of this new apomorphine sublingual formulation, along with an inhaled formulation under development, will broaden the treatment options for off periods," writes Dr. Angelo Antonini from University of Padua, Padua, Italy, in an editorial.
"Because oral and inhaled routes of delivery provide rapid but short-term benefit, physicians should be aware that the acute administration of levodopa and apomorphine increases pulsatile stimulation of dopamine receptors and can worsen dyskinesia or be associated with behavioral changes, including dopamine dysregulation syndrome and impulse control disorders," he said.
"The results from Olanow and colleagues' study are encouraging and support the use of sublingual apomorphine film as a therapeutic option to improve fluctuations in most patients with Parkinson's disease," Dr. Antonini concludes. "However, because of the high rate of oropharyngeal adverse events, long-term safety needs to be monitored once the product is registered and available for chronic use in patients with Parkinson's disease."
Dr. Olanow did not respond to a request for comments.
Cynapsus Therapeutics and Sunovion funded the study, employed four authors of this report, and had various relationships with the other eight authors.
SOURCE: http://bit.ly/2TeCH8W and http://bit.ly/2TdunpS Lancet Neurology, online December 6, 2019.
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