Promising Outcomes of Original Grant:
Intrapulmonary delivery of levodopa results in rapid, consistent and predictable augmentation of plasma levodopa levels in both healthy volunteers and subjects with Parkinson’s disease. The unique pharmacokinetic profile translates into rapid and durable improvement in motor function without worsening dyskinesia in Parkinson’s patients. Results from prior clinical studies enabled dose selection for this, Phase IIb study of CVT-301, Civitas’ proprietary inhaled levodopa, which is being developed as a treatment to provide rapid relief of intermittent "off" episodes.
Objectives for Supplemental Investigation:
The objective of this study is to demonstrate that inhaled levodopa safely provides rapid symptomatic relief of "off" episodes during chronic, at-home use. The clinical benefit of adjunct CVT-301 use will be quantified both in the clinic, by evaluation of time course of change in UPDRS motor score following drug administration, and “at-home” by evaluation of the time to "on" following drug administration upon the emergence of "off" symptoms. This work is part of the continued clinical development of CVT-301 and will investigate, for the first time, its use at home as an adjunct to a patient’s standard combination levodopa and decarboxylase inhibitor (for example, carbidopa) oral regimen.
Importance of This Research for the Development of a New PD Therapy
This study is part of an integrated project plan to develop a new treatment for Parkinson’s patients to address an unmet medical need. Successful results should enable the study of CVT-301 in pivotal Phase III studies.
CVT-301 is a dry powder, aerosol formulation of levodopa being developed for the treatment of OFF episodes in PD patients already taking a standard oral regimen of levodopa/carbidopa. A Phase IIB study of CVT-301 adjunct to a scheduled daily regimen was designed to investigate the safety and efficacy of CVT-301 when self-administered “as needed” by patients for the treatment of OFF episodes. Patients were permitted to use CVT-301 up to three times a day to treat their emerging OFF episodes over a one-month period of observation. Two doses of CVT-301 were studied; these doses delivered approximately 35mg and 50mg levodopa to the lung, respectively.
86 PD patients who experienced frequent OFF periods were administered CVT-301 or placebo. Clinically significant and statistically significant improvements in motor response, as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) Part 3 motor score, were observed with onset of benefit apparent at about 10 minutes post-dose. In addition, use of CVT-301 resulted in significant improvements in subjective motor response. Significant improvements in OFF time without an increase in time ON with dyskinesia were recorded by patients.
CVT-301 was generally safe and generally well tolerated in both doses. There were no adverse changes in any respiratory endpoints.
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