SAN DIEGO -- Parkinson's patients appear to overcome morning akinesia rapidly with subcutaneous injections of apomorphine when compared with taking the first dose of levodopa, researchers reported here.
In a post hoc analysis of the so-called trial, about 65% of patients self-administering apomorphine responded to treatment within 20 minutes -- compared with 1% of patients taking levodopa, reported , professor of neurology at the Keck Medical Center at the University of Southern California Los Angeles.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Post-hoc analysis of a phase IV, multicenter, open-label trial of Parkinson's patients found that subcutaneous injections of apomorphine acted faster and more reliably than levodopa at relieving morning akinesia.
- It should be noted that these results were part of a post-hoc analysis and that administration of apomorphine was open label.
Furthermore, at his poster presentation at the annual , Lew demonstrated that 83% of patients receiving apomorphine responded at 30 minutes compared with 3% of patients during a levodopa baseline periods.
Even at 45 minutes the difference remained substantial with 94% of the apomorphine patients responding compared with 30% of the patients taking levodopa in the baseline period. As a post hoc analysis, statistically calculations were not performed, Lew said.
"Patients with morning akinesia cannot move well and are faced with up to an hour delay before levodopa dosing becomes effective," he told 鶹ý. "Apomorphine was found to provide rapid and reliable turning-ON, bypassing the oral route for patients with morning akinesia."
Apomorphine had been approved for use in Parkinson's disease for more than a decade, but it does not have an indication for treatment of morning akinesia. Lew said he would have no problem prescribing subcutaneous apomorphine for his patients who complained of morning akinesia.
In addition to its ability to act more quickly than levodopa in the morning, the researchers also noted that as an injected agent it bypasses the gastrointestinal route and may prevent some adverse events.
"Apomorphine was also found to provide a more reliable response," Lew said. "Whereas 74% of patients reported that they consistently turned ON within 30 minutes of apomorphine injections, no patient on levodopa in the baseline analysis reported that they consistently turned ON within 30 minutes." Consistency in this context meant they achieved ON status within 30 minutes on at least 75% of diary days.
In commenting on the study, director of the Parkinson's Disease and Movement Disorder Center at the University of South Florida Tampa, said, "This is a reasonable treatment for patients with morning akinesia."
However, Hauser told 鶹ý, "There are many patients who have problems with needles and for them other forms of apomorphine such as sublingual administration may be helpful as well."
Lew and colleagues enrolled 127 patients into the study; 97 completed the study, and 88 patients are included in the analysis. The mean age of the participants was 65.2 years, and 66% of the subjects were men. The mean duration of Parkinson's disease in the patients was 11.63 years; they reported having morning akinesia for about 2 to 3 years.
In the overall study, patients were enrolled in the phase IV, multicenter, open-label trial of patients with morning akinesia due to delayed or unreliable onset of levodopa action. The post hoc analysis used responded analyses to assess the predictability of subcutaneous injections compared with usual levodopa therapy.
In performing the study, patients first completed a 7-day baseline period in which they recorded their daily first morning time to onset of action following their regularly scheduled morning dose of levodopa. At the end of the baseline period, patients returned to the clinic for apomorphine titration over a maximum period of 11 days. The dose of apomorphine was gradually increased from 0.2 mL to a maximum of 0.6 mL.
Once the optimal dose of apomorphine was determined, patients were instructed to self-inject apomorphine at their regularly scheduled levodopa morning does time during a 7-day treatment period. Diaries were maintained for the first hour after administration of the drugs at 5-minute intervals. The diaries were used as the basis for determining when ON status was achieved.
"Responder analyses demonstrated a quicker time to ON with apomorphine versus levodopa," Lew reported. "In addition to being an effective treatment to reduce daily OFF time, apomorphine injection also has clinical utility to treat morning akinesia."
Disclosures
The study was funded by US WorldMeds and Britannia Pharmaceuticals Limited.
Lew disclosed relevant relationships with Teva, US WorldMeds, Merz, UCB, Acadia, Auspex, Lundbeck, AbbVie, Synosia Pharmaceuticals, Ipsen, Pharma two B, Civitas, Biotie, Cynapsus, Amarantus and Pfizer.
Hauser disclosed relevant relationships with Abbott, AbbVie, Addex, Allergan, AstraZeneca, Biotie, Ceregene, Chelsea, Civitas, Eli Lilly, GE, Impax, Intec, Ipsen, Isis, Knopp, Link Medicine, Lundbeck, LZ, Medivation, Merz, Neurocrine, Noven, Pfizer, Schering-Plough, Straken, Targacept, Teva, UCB, Upsher-Smith, US WorldMeds, Vita-Pharm, XenoPort and Zambon.
Primary Source
International Congress on Parkinson's Disease and Movement Disorders
Source Reference: Lew M, et al "Predictability of response to apomorphine subcutaneous injections: Responder analyses from the AM‐IMPAKT trial" MDS 2015; Abstract 259.