|
Investigators/Authors: Martin Freed, MD, Richard Batycky, PhD, Civitas Therapeutics, Inc.
Objective: Oral levodopa pharmacokinetics (PK) is subject to excessive within- and between-subject variability, reflecting challenges inherent to gastrointestinal (GI) delivery. Aerosol delivery of levodopa (LD) bypasses the GI tract and should significantly reduce the time to onset and improve PK consistency thereby optimizing therapeutic benefit when used with standard oral therapies. CVT-301 is a proprietary dry powder LD formulation that is optimized to deliver a precise dose to the lung for rapid, predictable and consistent LD absorption. Our objective is to demonstrate more rapid and consistent LD exposure and improved motor function following adjunct CVT-301 administration, compared to oral.
Methods/Design: This project is designed to demonstrate the PK attributes of intrapulmonary levodopa delivery compared to standard oral administration and to investigate the pharmacodynamic (Pdyn) benefit of adding intrapulmonary levodopa to a standard oral regimen for Parkinson’s Disease patients. CVT-301 will be investigated first in healthy adult volunteers. In a single ascending dose, cross over design, the safety (including pulmonary safety) and PK of levodopa will be assessed comparing CVT-301 to oral levodopa. Following selection of dose(s), CVT-301 will be studied in Parkinson’s disease patients as an adjunct to their standard oral therapy. In a placebo-controlled, cross-over design, the safety, levodopa PK profile and PDyn effects (i.e., motor responses) will be assessed, comparing CVT-301 to oral levodopa and placebo.
Relevance to Diagnosis/Treatment of Parkinson’s disease: Inconsistent levodopa exposure is a major factor contributing to the development of both motor fluctuations and dyskinesias. As an adjunct to standard oral therapies, CVT-301 may facilitate consistent levodopa exposure and improve therapeutic benefit of the most important anti-parkinsonian drug. Such a product that provides rapid, predictable and consistent levodopa exposure would be a major breakthrough in the Symptoms & Side Effects treatment of Parkinson’s disease.
Anticipated Outcome: Two key outcomes are anticipated from this project which will accelerate future clinical investigation of CVT-301. First, it is expected that the pharmacokinetic attributes of CVT-301 in humans will be consistent with those observed in pre-clinical models. Second, it is expected that adjunct administration of CVT-301 will enable more rapid and consistent levodopa exposure, leading to improved therapeutic benefit to Parkinson’s disease patients.
Back to Top
|
