title: Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson's disease.
abstract: OFF episodes negatively impact quality of life in patients with Parkinson's disease (PD). There remains a need for an acute, effective, noninvasive treatment.
  
  
  
  APL-130277 is a sublingually administered apomorphine oral strip.
  
  
  
  The authors conducted a phase 2, open-label, proof-of-concept study. Patients presented to clinic in the morning in the practically defined OFF state and were dosed with APL-130277 10 mg. Assessments of OFF or ON state and MDS-UPDRS part III were conducted predose and at 15, 30, 45, 60, and 90 minutes. If a full ON was not achieved within 3 hours, the dose was increased in 5 mg increments until a full ON was achieved or to a maximum dose of 30 mg. Patients could be dosed up to two times a day over 3 days. Patients were pretreated with trimethobenzamide for 3 days, which was continued during the study.
  
  
  
  Of 19 patients, 15 (78.9%) achieved a full ON response. All 15 achieved a full ON response within 30 minutes and 6 of the 15 patients (40.0%) achieved a full ON response within 15 minutes. The mean (SD) duration of ON was 50 (19.4) minutes. Of the 15 patients, 9 (60.0%) remained fully ON for ≥90 minutes. There were no discontinuations as a result of an adverse event. The most common adverse events were dizziness (36.8%), somnolence (31.6%), and nausea (21.1%).
  
  
  
  This was the first study of a new sublingual apomorphine formulation in PD patients. In this open-label study, APL-130277 appeared to provide a convenient, rapid, and reliable method for treating OFF episodes. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
authors.affiliation: University of South Florida Health Byrd Parkinson's Disease and Movement Disorders Center of Excellence, Tampa, Florida, USA. rhauser@health.usf.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.affiliation: Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
authors.affiliation: Cynapsus Therapeutics, Inc, Toronto, Ontario, Canada.
authors.forename: Bruce
authors.initials: B
authors.lastname: Dzyngel
authors.affiliation: Cynapsus Therapeutics, Inc, Toronto, Ontario, Canada.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bilbault
authors.affiliation: Barrow Neurological Institute, Phoenix, Arizona, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Shill
authors.affiliation: Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Isaacson
authors.affiliation: Cynapsus Therapeutics, Inc, Toronto, Ontario, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Dubow
authors.affiliation: Cynapsus Therapeutics, Inc, Toronto, Ontario, Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Agro
mesh_terms: D000286:Administration, Sublingual; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001058:Apomorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000188:drug therapy*; D000075082:Proof of Concept Study
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007980:Levodopa; D001058:Apomorphine
keywords: APL-130277; OFF periods; Parkinson's disease; apomorphine; fluctuations; sublingual; treatment