Indirect comparison of apomorphine sublingual film and levodopa inhalation powder for Parkinson's disease ‘OFF’ episodes

Abstract

Aim: To compare efficacy of apomorphine sublingual film (APL) and levodopa inhalation powder (CVT-301) for ‘on-demand’ treatment of Parkinson's disease ‘OFF’ episodes. Patients & methods: Patient-level data from an APL pivotal study were re-weighted to match average baseline characteristics from a CVT-301 study (SPAN-PD). Placebo-adjusted treatments were compared at week 12. Results: Improvements in predose Unified Parkinson's Disease Rating Scale Part III scores were significantly larger for APL versus CVT-301 at 60 min postdose (least squares mean difference-in-difference: -8.82; p = 0.002); difference at 30 min favored APL but was not statistically significant (-4.46; p = 0.103). Total daily ‘OFF’ time reductions were significantly larger for APL versus CVT-301 (-1.31 h; p = 0.013). Conclusion: Results suggest APL treatment may lead to improved efficacy versus CVT-301.

Intermittent Apomorphine Use for off Period Rescue in Parkinson's Disease: A Pragmatic Review of over Three Decades of Clinical Experience

“…Recently, an indirect analysis of data from separate studies showed that sublingual apomorphine was superior to the recent introduced inhaled levodopa, improving UPDRS III scores at 30 and 60 minutes. 12 Unlike SC apomorphine which is available worldwide, sublingual apomorphine is only available in the United States and Canada, where it is licensed for sale in 10, 15, 20, 25, or 30 mg film strips. The starting dose recommended is 10 mg, followed by 5 mg increases after 72 hours, and the maximum single dose is 30 mg.…”

“…Renewed interest in use of sublingual and intranasal apomorphine as an alternative to the SC route, is further supported by promising results from recent high‐quality trials, 54–56,66,67 especially for individuals with needle phobia. Recently, an indirect analysis of data from separate studies showed that sublingual apomorphine was superior to the recent introduced inhaled levodopa, improving UPDRS III scores at 30 and 60 minutes 12 . Unlike SC apomorphine which is available worldwide, sublingual apomorphine is only available in the United States and Canada, where it is licensed for sale in 10, 15, 20, 25, or 30 mg film strips.…”

“…Although direct comparative trials with dispersible or inhaled forms of levodopa as a rescue agent are lacking, indirect comparisons suggest apomorphine's speed of action and reliability to be superior. 12 In the last 10-years, there has been a resurgence of interest in alternative routes of apomorphine administration for off-period rescue therapy. We therefore set out to review and summarize published evidence on intermittent apomorphine use for offperiod rescue by conducting a structured literature search, in order to highlight its usefulness in clinical practice.…”

“…In clinical practice, prompt and effective reversal of disabling off periods during the waking day, and nocturnal and early morning akinesia are necessary. Although direct comparative trials with dispersible or inhaled forms of levodopa as a rescue agent are lacking, indirect comparisons suggest apomorphine's speed of action and reliability to be superior 12 …”

Drugs to the Rescue: Comparison of On-Demand Therapies for OFF Symptoms in Parkinson’s Disease

“…In a comparison of the pivotal trials for inhaled LD and sublingual apomorphine Thach et al [ 42 ] compared placebo-adjusted treatments at week 12 from the SPAN-PD trial [ 43 ] and the CTH-300 trials [ 41 ]. There was no significant difference in the UPDRS part III score at the 15–20 minutes or the 30 minutes time points.…”