Objective/Rationale:
The objective of this project is to develop gastric retentive controlled-release tablets of levodopa/carbidopa that will result in more constant blood levels of levodopa compared to current levodopa therapy. Maintaining constant blood levels of levodopa should result in a reduction of side effects (dyskinesia, uncontrolled movements involving several joints when blood levels are to high and akinesia, lack of initiation of movement when blood levels are to low) that are caused by current levodopa therapy.
Project Description:
Gastric retentive tablet formulations that release levodopa and carbidopa at a constant rate over times ranging from four to eight hours will be administered to animal models of Parkinson's following a meal. Blood samples will be obtained from the animals for up to 24 hours following administration of the tablets and the concentrations of levodopa and carbidopa will be determined. The concentration data obtained from the gastric retentive tablets will be compared to a formulation of levodopa/carbidopa (Sinemet® CR) that is currently being used in the treatment Parkinson's disease patients.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
As stated above, maintaining constant blood levels of levodopa in the therapeutic range should result in a reduction of side effects (dyskinesia, uncontrolled movements involving several joints when blood levels are to high and akinesia, lack of initiation of movement when blood levels are to low) that are caused by current levodopa therapy. An additionally benefit of providing a constant plasma levels of levodopa is disease progression may be slowed.
Anticipated Outcome:
This preclinical program will result in selection of two to three tablet formulations to be advanced to clinical studies in Parkinson’s disease patients.
Final Outcome
A controlled-release formulation of levodopa was tested in vivo, and demonstrated superior pharmacokinetic properties. Depomed has completed a Phase 1 clinical trial examining two of these formulations. The company is now optimizing one of the formulations and will initiate a second Phase 1 clinical trial.
Results from both the pre-clinical and clinical studies were presented at the World Federation of Neurology World Congress on Parkinson’s Disease and Related Disorders in Miami, Florida, on December 15, 2009.