Intec Pharma - Levodopa GR for Parkinson's disease

Levodopa GR for Parkinson's disease

Since its introduction in the 1960s, Levodopa (LD) has been the most widely used and effective drug for the symptomatic therapy of Parkinson's disease (PD).
However, chronic Levodopa therapy becomes problematic with the development of motor complications, which can be disabling, difficult to treat, thus limiting the usefulness of the drug.

These complications include:

”Off periods”
Dyskinesias

Both of these phenomena are believed to be a result of the pulsatile stimulation of striatal dopamine receptors, caused by fluctuations in Levodopa blood concentrations between doses. To date, a satisfactory sustained-release formulation of Levodopa has not been possible because LD is absorbed mainly in the upper intestines and a slow release product that has passed the area of absorption is not effective.

The Accordion Pill Carbidopa/ Levodopa (AP-CD/LD) is a gastric retentive dosage form (GRDF) containing CD/LD with Immediate and controlled release. The IR component is designed to provide a rapid onset, while the CR component's role is to provide true – long-acting properties, due to the prolonged release of the drug towards its absorption site, in the upper GI.

Phase I

AP-CD/LD has demonstrated statistically significant superiority, over the current marketed IR and CR versions of CD/LD.

Phase IIA

Phase IIA was conducted in two leading Israeli medical centers, in 12 early stages PD patients . The objective was to evaluate the pharmacokinetic profiles, during the day, of AP-CD/LD 50/250mg, taken BID, in a crossover fashion with four-times a-day 25/125mg immediate release CD/LD (Dopicar® Teva Pharmaceuticals), each taken for 7 days.

According to Intec's clinical advisors in the field of Parkinson’s disease, the steady-state profile of the Levodopa plasma levels which was achieved in Parkinson's disease patients, treated with the Accordion Pills, is unprecedented, compared to all currently available oral Levodopa formulations.

Phase IIB

Phase IIB was conducted in three leading Israeli medical centers: Sourasky Tel-Aviv Medical Center (Ichilov), Rabin Medical Center (Beilinson) and Sheba Medical Center (Tel Hashomer). 12 advanced stages Parkinson's disease patients participated in this study. The patients were treated with the AP-CD/LD product for a period of one week, and then crossed over for a second week in which they were treated with their currently marketed Levodopa treatment regimen (in a randomized manner). The efficacy of the AP-CD/LD product was tested during 16 hours (waking hours) a day, in comparison to the current treatment regimen. The safety of the AP-CD/LD was also tested during this study.

In 10 patients who completed the study in accordance with the study protocol, a statistically significant decrease in 'OFF time' and statistically significant reduction in the number of doses per day were achieved.

In 80% of these patients an average reduction of about 35% in the OFF time (2.96 hours compared to 4.48 hours with their current treatment) was achieved, which is statistically significant. The number of daily doses in this patient group was reduced by half (from 6.0 times per day to 3.2 times per day). With respect to product safety, the Accordion-Pill-Levodopa product once again proved its good safety profile and no significant adverse effects were reported during the study.

To the Company's knowledge, the intermediate results achieved in this study, with respect to the reduction in the number of daily doses together with the reduction in the duration of motor dysfunction, are unprecedented in comparison to currently marketed orally administered Levodopa products.

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