Study Rationale:
Apomorphine is a drug that is used to control “off” episodes in people with Parkinson’s disease. At present, the drug is given by injection under the skin and starts to relieve symptoms within 20-30 minutes. APL-130277 is a new formulation of apomoprhine that is given as a thin-strip film that is placed under the tongue. APL-130277 appears to work as quickly as the injection. This study will examine the effect of APL-130277 in people with Parkinson’s disease to determine which dose relieves the symptoms of their off episode.
Hypothesis:
The study will determine what dose is associated with relief of off episodes in people with Parkinson’s disease.
Study Design:
Patients will enter the clinic in an off state. They will start with a dose of 10mg APL-130277. If the off episode is not relieved, the patient will continue up the dose regimen until the off episode is properly relieved as assessed by the study doctor. There are five doses available to be tested, and patients have up to five days to find the dose that relieves the off episode.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Apomoprhine is an effective drug but is limited in its use because it is given as an injection. APL130277 is given as a thin-strip film under the tongue. Such an approach has the potential to allow people to manage their off episodes with an effective and patient-friendly approach.
Next Steps for Development:
After completing this study, APL-130277 will complete the other necessary clinical studies to support its approval by the FDA. These studies will be performed in the United States and include people who have Parkinson’s disease who suffer from off episodes. These studies are planned to be completed in time for APL-130277 to be submitted for FDA approval in late 2015.
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Final Outcome
Efficacy Conclusions: Overall, 15 out of 19 patients dosed with APL-130277 converted from the “off” to the full “on” state. All 15 turned fully “on” within 30 minutes of dosing, and six within 15 minutes. Thirteen of the 15 remained fully “on” for at least 30 minutes and nine remained “on” for at least 60 minutes. A range of doses were used but more than half needed the lowest two doses (10 and 15 mg). Of the four patients who did not achieve a full “on”, two were dosed incorrectly and two reached 30 mg without safety or tolerability concerns. A large, statistically significant improvement in motor function as measured by the MDS-UPDRS Part III absolute and percent change was seen at 15, 30, 45, 60 and 90 minutes after dosing with APL-130277. APL-130277 provided rapid, clinically meaningful improvement in motor function for PD in the “off” state, much of which was sustained through 90 minutes.
Safety Conclusions: Overall, APL-130277 was safe and well tolerated. Most adverse events seen were known adverse events associated with dopaminergic treatment, were mild to moderate in severity, and transient. There was no apparent dose-response relationship in adverse events, and there were no related serious adverse events. Only one out of 19 patients experienced symptomatic orthostatic hypotension. There were no adverse events of dyskinesia or local mucosal irritation, and no patients discontinued due to an adverse event.
September 2015