Objective/Rationale:
The objective of this project is to develop an extended-release capsule of levodopa/carbidopa (IPX066) that will result in constant blood levels of levodopa compared to current extended release 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.
Project Description:
Investigational extended-release capsule and commercially available extended release tablet formulations that deliver levodopa and carbidopa with different release profiles will be administered to Parkinson’s disease patients. An objective Parkinson’s disease measurement (OPDM) will be conducted to compare the effectiveness of the two treatments. In addition, researchers will collect UPDRS data every hour. The OPDM system ratings will be correlated to the classic rating scales and validate OPDM rating scales. Blood samples will be obtained for up to six hours following administration of the tablets and capsules, and the concentrations of levodopa and carbidopa will be determined. Another aspect of this research will provide comparison between two controlled release levodopa products.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
As stated above, maintaining constant blood levels of levodopa in the therapeutic range for treating Parkinson’s disease symptoms should have an added benefit of reducing dyskinesia and akinesia that are caused by current levodopa therapy.
Anticipated Outcome:
This study shall provide comparative information about two oral extended-release products and help validate some new objective rating scales.
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Final Outcome
Similar to other levodopa products, further adjustment of IPX066 doses for individual patients is necessary to maximize the effects. The conversion ratios were slightly lower for the three patients who were treated with extended-release levodopa (ER LD) alone (median 1.6 vs. 1.7). In the OPDM subset (IPX066 vs. ER LD), “on” time without troublesome dyskinesia was significantly longer with IPX066 than with ER LD treatment (4.29 vs. 2.63 hours), and the “off” state was correspondingly shorter during IPX066 treatment (1.67 vs 3.17 hours. Similar relationships were observed between plasma levodopa concentrations and the UPDRS Part III scores as well as mobility scores; however, no apparent relationship was observed between plasma levodopa concentrations and dexterity scores. No statistically significant differences were noted between IPX066 and ER LD for both mobility and dexterity assessments in this small sub-study. Consistent with the results of other adequate and well-controlled IPX066 trials, majority of the subjects (>79%) preferred IPX066 treatment over their previous treatments at all assessed study visits.
May 2014