These complications include:

• ”Off periods”
• Dyskinesias

Both of these phenomena are believed to be associated with fluctuations in Levodopa plasma concentrations. To date, a satisfactory sustained-release formulation of Levodopa has not been possible because LD is absorbed mainly in the upper intestines and hence a slow release product that has passed the area of absorption is not effective. 

The Accordion Pill Carbidopa/Levodopa (AP-CD/LD) is a designated oral delivery platform developed by Intec Pharma Ltd. which contains Carbidopa and Levodopa in different doses, for the treatment of the various stages of the disease. The AP-CD/LD is designed to stabilize Levodopa plasma levels and thereby bring about, for the first time, a dramatic reduction in motor complications and reduce the frequency of daily dosing, using oral treatment. 

Phase IIb

Group 1

This study 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 AP-CD/LD 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 motor complications, are unprecedented in comparison to currently marketed orally administered Levodopa products.

Group 2

This study was conducted in six medical centers: Sourasky Tel-Aviv Medical Center (Ichilov), Rabin Medical Center (Beilinson), Sheba Medical Center (Tel Hashomer), Rambam Medical Center in Haifa, The Hadassah University Medical Center and Brazilai Medical center. 17 advanced Parkinson's disease patients participated in this study. The patients were treated with the Accordion-Pill-Carbidopa/Levodopa (AP-CD/LD) product for a period of three weeks, and then crossed over (randomized) for a second three week period in which they were treated with their personal currently marketed Carbidopa/Levodopa treatment regimen.  The efficacy of the AP-CD/LD product was tested, in comparison to the current treatment regimen, during 24-hour periods. The primary end-point of the trial was the reduction of Total OFF Time compared to the current treatment regimen. In addition, the safety of the AP-CD/LD was also tested.

In 16 patients who completed the study in accordance with the study protocol, a statistically significant decrease in Total Off Time of 1.9 hours (44%) was achieved. With the AP-CD/LD treatment, the Total OFF Time was 2.4 hours compared to 4.3 hours with the current treatment regimen. This result was of statistical significance (P<0.0001). Total Good On Time was increased by 2.1 hours, with the AP-CD/LD treatment (P=0.0001). In addition, a significant reduction (of statistical significance), in the total number of Levodopa daily doses from 6.3 to 3.4 was achieved.

In 12 of these 16 patients (75%), an average reduction of 2.9 hours (55%) of Total OFF Time, over 24-hour period, was achieved. With the AP-CD/LD treatment, Total  Off Time was 2.3 hours compared to 5.2 hours with the current treatment regimen  (P<0.0001). Total Good On Time was increased by 2.8 hours, with the AP-CD/LD treatment (P<0.0001).

With respect to the AP-CD/LD safety, the product once again proved its good safety profile and no significant adverse effects were reported during the study.

The rate of the reduction of Total Off Time, achieved in this group, was twice the rate achieved in the first group of Phase IIb (a reduction of 2.9 hours in comparison to 1.5 hours). The improvement resulted from the extension of the use of the AP-CD/LD from one week to three weeks, which indicates the potential of the AP-CD/LD to dramatically improve the efficacy of the drug following a long term use. 

To the Company`s best knowledge, the aforesaid intermediate results are unprecedented, in comparison to the oral Levodopa products which are marketed today. The Company has developed three different strengths of the AP-CD/LD, two of which have been tested so far. The third strength is being tested in the third and last group of Phase IIb, whose results are expected to be published during the fourth quarter of this year.

According to Dr. Peter LeWitt, a Key Opinion Leader for Parkinson Disease, Director of the Parkinson’s disease and Movement Disorders Program at Henry Ford Hospital, Detroit, Michigan USA and the Company's clinical advisor, "These clinical results are consistent with pharmacokinetic evidence that the AP-CD/LD formulation extends anti-Parkinsonian effect of Levodopa in patients with wearing-off. The extent of improvement in “OFF” time (without an increase of troublesome dyskinesias) obtained in this study, indicates a substantial clinically-meaningful effect, with considerable promise for helping a common problem for the advanced Parkinson’s disease patient".

The Company estimates that the highly statistically significant results achieved so far shall improve the chances of success in the next phases and may have significant positive implications on the scope, cost and duration of the Phase III clinical trial.

The Company's estimations for future development, expected clinical trials and sales forecasts, with respect to the Company's products, is forward looking information that is based on information in the Company's hands today with respect to drugs development potential and the indications it has received from relevant health care authorities. These estimates may not be realized, in whole or in part, and/or may be realized differently than estimated, as a result of different factors, including failure to reach the objectives of the studies and/or schedules and/or necessary funding for further drug development and failure to obtain regulatory approvals required for further development, failure to reach collaboration with international companies and other factors which are not within the Company's control and the materialization of any of the risk factors that relate to the Company's activities.