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Sublingual Apomorphine Improves Symptoms of Parkinson’s Disease in Early Trials
Data from early clinical studies, presented at the 19th International Congress of Parkinson’s Disease and Movement Disorders (MDS) in San Diego, California, have shown that APL-130277 (Cynapsus Therapeutics) significantly improved symptoms of Parkinson’s disease (PD), rapidly turned patients from the “off” state to the “on” state, and was generally safe and well tolerated.
In the “on–off” phenomenon associated with PD, patients receiving sustained levodopa treatment fluctuate between a state of mobility (“on”) and one of immobility or “freezing” (“off”) as the effects of therapy slowly dissipate.
APL-130277 is a sublingual apomorphine thin film under development for the on-demand treatment of “off” episodes associated with PD.
Study CTH-105 was a phase II, open-label, multicenter trial in which sublingual APL-130277 was assessed in 19 patients with PD who experienced “off” episodes, with a total duration of at least 2 hours of “off” episodes daily. Of the 19 patients dosed, 15 (79%) achieved a full “on” response. Of the four nonresponders, two were dosed incorrectly, and two were dosed up to the maximum available dose (30 mg). The patients were rapidly converted from the morning “off” state to the full “on” state, with 100% of responders turning fully “on” within 30 minutes and 40% within 15 minutes.
Study CTH-104 was a phase I, single-center trial that evaluated the pharmacokinetic (PK) profile, safety, and tolerability of a single dose of sublingual APL-130277 (25 mg) in healthy volunteers. Eleven subjects were dosed with APL-130277 and two with placebo. The 25-mg dose demonstrated a favorable PK profile to support a rapid and sustained effect for acute relief of “off” episodes in PD patients. The time to reach the known minimum efficacious plasma apomorphine concentration was achieved in less than 10 minutes, and apomorphine levels were maintained above this concentration for more than 2.5 hours.
Study CTH-103 was a phase I, single-center, crossover trial that evaluated the PK profile, safety, and tolerability of two doses of sublingual APL-130277 (10 mg and 15 mg) compared with that of subcutaneous apomorphine (2 mg and 3 mg) in healthy volunteers. Sublingual APL-130277 reached known therapeutic apomorphine plasma levels comparable with those of subcutaneous apomorphine, with a longer duration over the minimum efficacious plasma concentration. Sublingual APL-130277 also demonstrated a lower maximal concentration and a less-steep rise to the maximal concentration compared with subcutaneous apomorphine, leading to fewer dopaminergic adverse events.
Source: Cynapsus Therapeutics; June 25, 2015.