C Warren Olanow1, Fabrizio Stocchi2, Elizabeth L Peckham3, Maria Francesca De Pandis4, Ken Sciarappa5, Bradford Navia5. 1. Mount Sinai School of Medicine, New York, NY, USA; Clintrex, Research Corporation, Sarasota, FL, USA. Electronic address: warren.olanow@clintrex.com. 2. University and Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy. 3. Central Texas Neurology Consultants, Round Rock, TX, USA. 4. San Raffaele Cassino, Tosinvest Sanità, Cassino, Italy. 5. Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
Abstract
INTRODUCTION: Apomorphine sublingual film is approved for the "on-demand" treatment of "OFF" episodes in Parkinson's disease (PD). Patients must undergo dose titration to determine their most effective and tolerable dose. We assessed whether higher doses than those that provide an initial "ON" response could yield more effective treatment. METHODS: Patients with PD were assessed in the "OFF" state and the apomorphine sublingual film dose was titrated to a level that provided a tolerable "ON" response. The dose was then increased by up to two dose levels, if tolerated. A comparison in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III scores was made following administration of the dose that provided the initial "ON" response and following the higher dose. Treatment-emergent adverse events were also reported. RESULTS: Thirty-five patients were titrated to higher apomorphine sublingual film doses than those that provided an initial "ON" response. A mean improvement in MDS-UPDRS Part III score was observed compared with the initial dose of 5.6 points (P = 0.034), 4.4 points (P = 0.009), and 3.7 points (P = 0.018) at 30, 60, and 90 min postdose, respectively. Adverse events were mild or moderate and resolved with dose reduction without concomitant treatment. CONCLUSION: Higher doses of apomorphine sublingual film than those initially perceived to provide an "ON" response can be tolerated and provide additional improvement in motor function in many patients.
INTRODUCTION: Apomorphine sublingual film is approved for the "on-demand" treatment of "OFF" episodes in Parkinson's disease (PD). Patients must undergo dose titration to determine their most effective and tolerable dose. We assessed whether higher doses than those that provide an initial "ON" response could yield more effective treatment. METHODS: Patients with PD were assessed in the "OFF" state and the apomorphine sublingual film dose was titrated to a level that provided a tolerable "ON" response. The dose was then increased by up to two dose levels, if tolerated. A comparison in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III scores was made following administration of the dose that provided the initial "ON" response and following the higher dose. Treatment-emergent adverse events were also reported. RESULTS: Thirty-five patients were titrated to higher apomorphine sublingual film doses than those that provided an initial "ON" response. A mean improvement in MDS-UPDRS Part III score was observed compared with the initial dose of 5.6 points (P = 0.034), 4.4 points (P = 0.009), and 3.7 points (P = 0.018) at 30, 60, and 90 min postdose, respectively. Adverse events were mild or moderate and resolved with dose reduction without concomitant treatment. CONCLUSION: Higher doses of apomorphine sublingual film than those initially perceived to provide an "ON" response can be tolerated and provide additional improvement in motor function in many patients.
Authors: Fabrizio Stocchi; Elizabeth L Peckham; Maria Francesca De Pandis; Ken Sciarappa; Robert Kleiman; Felix Agbo; C Warren Olanow; David Blum; Bradford Navia Journal: Clin Pharmacol Drug Dev Date: 2022-07-28