Donald G Grosset1, Rohit Dhall2, Tanya Gurevich3, Jan Kassubek4, Werner H Poewe5, Olivier Rascol6, Monika Rudzinska7, Jennifer Cormier8, Alexander Sedkov8, Charles Oh8. 1. Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK. Electronic address: donald.grosset@glasgow.ac.uk. 2. Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 3. Neurological Institute Tel-Aviv Medical Center, Sourasky School of Medicine and Sagol School of Neuroscience, Tel-Aviv University, Israel. 4. Department of Neurology, University of Ulm, Ulm, Germany. 5. Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. 6. Clinical Investigation Center CIC1436, Department of Clinical Pharmacology and Neuroscience, NS-Park/FCRIN Network; CHU de Toulouse, Université de Toulouse3, INSERM, Toulouse, France. 7. Department of Neurology, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland. 8. Acorda Therapeutics, Inc., Ardsley, NY, USA.
Abstract
INTRODUCTION:CVT-301 is an orally inhaled levodopa therapy approved for the intermittent treatment of OFF episodes in Parkinson's disease patients who are taking a standard oral levodopa regimen. This open-label, randomized, controlled study over 12 months characterizes the safety, including pulmonary safety, of CVT-301 84 mg (nominal respirable levodopa fine-particle dose, 50 mg). METHODS:Patients experiencing motor fluctuations were randomized 2:1 to CVT-301 or an observational cohort (OC) receiving oral standard of care. Pulmonary safety was assessed using spirometry and carbon monoxide diffusion capacity (DLCO). Exploratory efficacy endpoints, assessed only for CVT-301, included change in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), patients achieving ON within 60 min and remaining ON at 60 min, Patient Global Impression of Change (PGIC) scale, and total daily OFF time. RESULTS: Of 408 patients randomized, 310 completed the study (204 in CVT-301 and 106 in OC). Mean 12-month changes from baseline for CVT-301 were -0.105 L (FEV1) and -0.378 mL/min/mm Hg (DLCO), and for OC were -0.117 L and -0.722 mL/min/mm Hg, respectively. Between-group comparisons were not statistically significant. For FEV1/FVC the 12-month change was -0.3 and -1.6, respectively, which was a significant between-group difference. However, between-group differences were not significant at 3 and 9 months and all changes from baseline were small (<2.0%). UPDRS-III scores improved from predose to 60 min postdose at all assessments; 80%-85% of patients switched ON within 60 min and remained ON; and >75% reported improvement in PGIC. OFF time decreased by 1.32-1.42 h/day. CONCLUSION:CVT-301 84 mg induced no clinically significant differences in pulmonary function compared with the OC. Improvements in motor scores, OFF time, and patient-reported outcomes support clinical efficacy for up to 12 months.
RCT Entities:
INTRODUCTION: CVT-301 is an orally inhaled levodopa therapy approved for the intermittent treatment of OFF episodes in Parkinson's diseasepatients who are taking a standard oral levodopa regimen. This open-label, randomized, controlled study over 12 months characterizes the safety, including pulmonary safety, of CVT-301 84 mg (nominal respirable levodopa fine-particle dose, 50 mg). METHODS:Patients experiencing motor fluctuations were randomized 2:1 to CVT-301 or an observational cohort (OC) receiving oral standard of care. Pulmonary safety was assessed using spirometry and carbon monoxide diffusion capacity (DLCO). Exploratory efficacy endpoints, assessed only for CVT-301, included change in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), patients achieving ON within 60 min and remaining ON at 60 min, Patient Global Impression of Change (PGIC) scale, and total daily OFF time. RESULTS: Of 408 patients randomized, 310 completed the study (204 in CVT-301 and 106 in OC). Mean 12-month changes from baseline for CVT-301 were -0.105 L (FEV1) and -0.378 mL/min/mm Hg (DLCO), and for OC were -0.117 L and -0.722 mL/min/mm Hg, respectively. Between-group comparisons were not statistically significant. For FEV1/FVC the 12-month change was -0.3 and -1.6, respectively, which was a significant between-group difference. However, between-group differences were not significant at 3 and 9 months and all changes from baseline were small (<2.0%). UPDRS-III scores improved from predose to 60 min postdose at all assessments; 80%-85% of patients switched ON within 60 min and remained ON; and >75% reported improvement in PGIC. OFF time decreased by 1.32-1.42 h/day. CONCLUSION: CVT-301 84 mg induced no clinically significant differences in pulmonary function compared with the OC. Improvements in motor scores, OFF time, and patient-reported outcomes support clinical efficacy for up to 12 months.