Six-month Oral Toxicity Study of the Accordion Pill™ of Carbidopa/Levodopa
Research Grant, 2013
The Accordion Pill™ is designated to significantly stabilize the pharmacokinetic profile of drugs with a narrow absorption window, such as levodopa. Regular controlled-release formulations do not provide an optimal solution – once the drug has passed the absorption window, it is no longer absorbed. The Accordion Pill of carbidopa/levodopa (AP-CD/LD) is a gastric-retentive dosage form designed to provide a significantly prolonged absorption of levodopa, for stable plasma levels, resulting in reduction of total "off" time and number of levodopa daily doses.
Following the successful completion of Phase II studies with AP-CD/LD, Intec Pharma intends to move the product forward to enter Phase III after a six-month pre-clinical study. Final report of that study is planned to be issued during Q1 2014. In parallel, the regulatory path of the AP-CD/LD is discussed with the relevant regulatory authorities and, accordingly, Phase III is planned to be initiated in mid-2014.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Phase II study results strongly demonstrate the relevancy of the AP-CD/LD project to the treatment of Parkinson's disease symptoms. Total "off" time over 24 hours was decreased with AP-CD/LD by approximately 45 percent in advanced PD patients. This reduction was achieved without increasing or with decreasing the "on" time of dyskinesia and with fewer levodopa doses per day. These significant improvements are in line with the AP-CD/LD's capability to provide continuous, stable levodopa plasma levels throughout the day with appropriate therapeutic pharmacokinetic levels of the drug.
The study would evaluate the toxicity of AP-CD/LD vs. placebo control or Sinemet (medication combining carbidopa/levodopa), when administered orally two or three times daily for 180 consecutive days, followed by one month of recovery. Intec expects that the study would provide the required toxicity evaluation needed to continue on the product's regulatory path.
The study results showed that pre-clinical models tolerated the Accordion PillTM when administered orally 100/1000 mg per day (50/500 mg b.i.d.) or 150/1200 mg per day (50/400 mg t.i.d.). There were no adverse effects associated with the Accordion Pill or the comparator Sinemet treatment. Overall, the Accordion Pill treatments resulted in fewer clinical signs than the Sinemet comparator.
The Phase III trial is recruiting: https://foxtrialfinder.michaeljfox.org/trial/4260/
VP R&D and Operations at Intec Pharma Ltd.
Location: Jerusalem, Israel