The objective of this project is to develop a gastric-retentive, extended-release tablet of levodopa/carbidopa (DM-1992) that will result in constant blood levels of levodopa compared to current therapy while reducing dosing frequency and maintaining effectiveness in controlling Parkinson’s symptoms. Additionally, maintaining constant blood levels of levodopa should result in a reduction of side effects (dyskinesia: uncontrolled movements when levels are too high) and symptoms (akinesia: lack of initiation of movement when levels are too low) that are caused by current therapy.
Two different gastric-retentive, extended-release tablet formulations that deliver levodopa and carbidopa with different release profiles over eight hours will be administered to Parkinson’s disease (PD) patients following a meal. Blood samples will be obtained for up to 24 hours following administration of the tablets, and the concentrations of levodopa and carbidopa will be determined. In addition, a finger tapping test will be conducted following each blood sample to determine effectiveness of the treatment. The blood concentration data and finger tapping results obtained after administration of the gastric-retentive tablets will be compared to a marketed non-gastric-retentive, extended-release formulation of levodopa/carbidopa that is currently being used in the treatment of PD patients.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
As stated above, maintaining constant blood levels of levodopa in the therapeutic range for treating PD symptoms should have an added benefit of reducing dyskinesia and akinesia that are caused by current levodopa therapy.
If successful, this study will result in selection of a tablet formulation to be advanced to later stage clinical efficacy and safety studies in PD patients.
This grant was selected by The Michael J. Fox Foundation staff to be highlighted via the Foundation’s Partnering Program.
Two extended-release formulations of levodopa/carbidopa that are retained in the stomach while gradually releasing the drugs were studied in PD patients. One of the formulations also contains an immediate release portion, which may provide a faster onset on action. This may be important in the event a patient misses a dose. Both formulations demonstrated sustained and smoother blood concentrations of levodopa, which in turn resulted in a better movement performance, as judged by a finger tapping test.
Presentations & Publications
Stolyarov ID, Illarioshkin SN, Ivashkova E, Irishina j, Zagorovskaya TB, Ershova MV, Chen C, Cowles, VE, Sweeney, M. Levodopa Pharmacokinetics and Pharmacodynamics Following Administration of Novel Gastric Retentive Extended-Release Formulations in Parkinson’s Disease Patients. Presented at The Movement Disorder Society’s 15th International Congress of Parkinson’s Disease and Movement Disorders, June 8, 2011.
Stolyarov ID, Illarioshkin SN, Ivashkova E, Irishina j, Zagorovskaya TB, Ershova MV, Chen C, Cowles, VE, Sweeney, M. Levodopa Pharmacokinetics and Pharmacodynamics Following Administration of Novel Gastric Retentive Extended-Release Formulations in Parkinson’s Disease Patients. The Movement Disorder Society’s 15th International Congress of Parkinson’s Disease and Movement Disorders, Late Breaking Abstract Program June 5-8, 2011, 4-5.
Chen C, Cowles VE; Sweeney M; Stolyarov D, Illarioshkin SN. Pharmacokinetics and Pharmacodynamics of Gastric Retentive Delivery of Levodopa/Carbidopa in Patients with Parkinson’s Disease. Submitted for publication to Clin Neuropharmacol June 2011.