Anti-nausea meds not necessary when starting Kynmobi
Researchers share analysis of Phase 3 clinical trial data
Medications to prevent nausea and vomiting usually are not necessary for Parkinson’s disease patients beginning treatment with Kynmobi (apomorphine hydrochloride), according to a recent analysis of Phase 3 clinical trial data.
Nearly 90% of patients who did not use these medications were still able to achieve an optimal Kynmobi dose and tolerate it well, with relatively low rates of nausea and vomiting.
Most cases of these symptoms were mild or moderate, and more than half of people who reported them did not continue to experience them with long-term treatment.
The study, “Dose Optimization of Apomorphine Sublingual Film for OFF Episodes in Parkinson’s Disease: Is the Prophylactic Use of an Antiemetic Necessary?” was published in the Journal of Parkinson’s Disease.
Parkinson’s disease is caused by the progressive loss of dopamine-producing nerve cells in the brain. As such, patients are commonly treated with levodopa or other therapies to replace or mimic the signaling chemical.
Apomorphine is one such treatment that aims to mimic dopamine’s effects. Injectable (Apokyn) and under-the-tongue, or sublingual (Kynmobi) formulations of apomorphine are approved for the prevention of motor symptom re-emergence between doses of levodopa, which are called “off” Â periods.
When starting these treatments, the dose typically is increased slowly until the best-tolerated and effective dose is reached.
As with other dopamine-replacing therapies, nausea and vomiting are common side effects of apomorphine. Antiemetics — medications to prevent nausea and vomiting — are sometimes recommended to prevent these side effects when initiating apomorphine treatment.
Post hoc analysis
Now, researchers in the U.S. conducted a post hoc (after-the-fact) analysis of data from an open-label Phase 3 clinical trial (NCT02542696) of Kynmobi to determine how often antiemetics were needed among patients beginning the under-the-tongue apomorphine therapy.
The study enrolled 449 adults with Parkinson’s, all of whom received Kynmobi — delivered as a thin film that dissolves on the tongue — up to five times per day.
Participants were either newly enrolled or rolled over from previous trials. More than half (60.4%) were using other dopamine-replacing therapies at the time they started Kynmobi.
During an initial dose optimization phase, Kynmobi was increased in 5 mg increments until an optimal dose (10-35 mg) was achieved, or a dose that enabled complete control of symptoms during “off'” periods.
The trial protocol initially required the use of trimethobenzamide, an antiemetic, during dose optimization, but this later became optional.
Overall, 88.4% of participants achieved an effective and tolerable Kynmobi dose. Antiemetic treatments were used at some point during dose optimization by 56.3% of participants.
Among patients who never used an antiemetic, 86.2% were still able to achieve an effective and tolerable dose. Nausea and vomiting were uncommon in this patient subset, occurring in 12.2% and 0.5% of patients, respectively.
For those who did use an antiemetic, 17% experienced nausea and 2.4% experienced vomiting.
In general, these symptoms occurred numerically less frequently among patients who were using other dopamine-replacing therapies at the time of starting Kynmobi, as well as men, smokers, patients with longer disease duration, and those with more severe disease.
Similar rates of these symptoms were observed among patients who had used Kynmobi previously compared with those who had not.
Moreover, the subgroup of patients enrolled in the trial after trimethobenzamide became optional saw similar rates of nausea and vomiting to the broader patient group, suggesting “that prophylactic trimethobenzamide may not be necessary for [Kynmobi] dose optimization,” the researchers wrote.
Across all cases of nausea and vomiting, most were mild or moderate, but one case of each was considered severe. Ultimately, 1.8% of participants stopped using Kynmobi due to nausea.
Of all patients who experienced nausea or vomiting during dose optimization, less than half continued to experience these symptoms during the trial’s maintenance phase, in which patients routinely received their optimized dose.
For those who did not have either symptom during dose optimization, 19% experienced it at some point during maintenance treatment.
Previous results
Consistent with previous analyses, the findings overall indicate that antiemetic treatment when optimizing Kynmobi “is not necessary for most patients,” the researchers wrote.
“Their use should be carefully considered in the context of cost, the burden on patients to take additional medications multiple times daily, and limited access,” the researchers wrote, particularly in light of the fact that trimethobenzamide is not readily accessible in the U.S.
Still, some patients may benefit from the treatments. “[T]he choice to use or not use an antiemetic should be evaluated in the context of anticipated risks and benefits,” the team concluded.
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