new research shows.
“The bottom line was that the majority of patients did not have dose-limiting nausea or vomiting,” said coinvestigator William Ondo, MD, from Houston Methodist Neurological Institute. “And although it really did not compare in a prospective, placebo-controlled manner use of [trimethobenzamide antiemetic] ... versus not using [it], anecdotally and based on historic data, nausea really seemed to be about the same even without the antinausea medication.”
The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
This study was the dose-titration phase to determine the effective and tolerable dose of the drug as part of a longer study looking at safety and efficacy.
Only 13% of patients experienced nausea and/or vomiting, and of those, 74% cases were of mild severity and 26% were of moderate severity. These rates of nausea/vomiting were lower than those seen when trimethobenzamide (Tigan, Pfizer) was needed to be administered during the titration period, at the discretion of the investigator.
This multicenter, ongoing, open-label, phase 3 study enrolled 176 patients (mean age, 64.4 years) who had idiopathic Parkinson’s disease for a mean of 8.0 years and had no prior exposure to SL-apo, with modified Hoehn and Yahr stage 1-3 disease (83% stage 2 or 2.5 during “on” time).
Study participants had Mini-Mental State Examination scores greater than 25, were receiving stable doses of levodopa/carbidopa, and had 1 or more (mean, 4.2) “off” episodes per day with a total daily “off” time of 2 hours or more. Patients with mouth cankers or sores within 30 days of screening were excluded.
Open-label dose titration occurred during sequential office visits while patients were “off,” with escalating doses of 10-35 mg in 5-mg increments to determine a tolerable dose leading to a full “on” period within 45 minutes. Patients self-administered this achieved dose of SL-apo for up to five “off” episodes per day with a minimum of 2 hours between doses for the full 48-week study period.
The study protocol prohibited antiemetic use except when clinically warranted at the investigator’s discretion. Of the 176 patients, 31 (18%) received the antiemetic trimethobenzamide and 145 (82%) did not.
Of the 176 patients, 76% received their effective and tolerated dose within the first three doses. Just over half (55%) received 10 mg or 15 mg. Only 24% received the highest doses of 25 mg or 30 mg.
About 52%of patients who received trimethobenzamide experienced treatment-related nausea and 13% experienced vomiting; in comparison, 13% not receiving trimethobenzamide had nausea and 1% had vomiting. About 10%of patients in the former group and none in the latter discontinued the study because of nausea and/or vomiting.
The apomorphine sublingual film has “the advantage of ease of use compared to the injectable form,” Dr. Ondo said. “I think the injectable form, purely based on anecdotal experience, might start to work a minute or 2 faster than the sublingual form, but overall I would say efficacy as far as potency of turning ‘on’ and consistency of turning ‘on’ is comparable.”
In addition to the known adverse effects of nausea, vomiting, and hypotension with the use of any apomorphine, he said that long-term use of the sublingual form can lead to gingival irritation. Two recommendations are to place the film in a different site and to use a more basic toothpaste, such as one containing baking powder, because irritation may result from the acidity of the apomorphine.