JERUSALEM—Intec Pharma Ltd. has announced that data collected from two Phase 1 studies of its proprietary Accordion Pill Carbidopa/Levodopa (AP-CD/LD) for Parkinson's disease were highlighted in a poster presentation at the American Academy of Neurology 2018 annual meeting (AAN 2018), underway in Los Angeles. The poster, entitled “Optimizing Delivery of Carbidopa/Levodopa via the Accordion Pill: Comparative PK and Safety From 2 Randomized Crossover Studies in Healthy Volunteers,” was presented yesterday evening by R. Michael Gendreau, M.D., Ph.D., Chief Medical Officer of Intec Pharma.
According to Intec’s website, “Levodopa is the most widely used therapy for Parkinson’s disease (PD). However, Levodopa treatment is associated with motor complications, mainly wearing “OFF” periods and LD-induced dyskinesia. PD patients experience wearing off between LD doses, due to the Short Term Duration of effect from each dose of LD. This phenomenon occurs roughly in parallel with the drug’s peripheral PK profile. Therefore, improving consistency in LD’s plasma levels becomes the major factor for improving anti-Parkinsonian control. Current formulations of LD provide only limited efficacy because LD’s absorption is confined to the upper part of the GI tract (narrow absorption window). The AP-CD/LD is a gastric-retentive dosage form containing carbidopa and levodopa in both immediate and controlled-release ways.”
The Phase 1 studies evaluated the pharmacokinetics (PK) and safety of AP-CD/LD versus immediate-release (IR) CD/LD (Sinemet) and under different meal conditions in healthy adults. IN 11 005 was a randomized, two-way crossover study in which healthy adults received a single dose of AP-CD/LD 50mg/500mg and two consecutive doses of IR-CD/LD 25mg/250mg (0 h and 4 h) following an overnight fast, with a 7-day washout between treatments. IN 14 001 was a randomized three-way crossover food-effect PK study in which healthy adults received a single dose of AP-CD/LD 50mg/500mg following high-calorie, low/medium calorie or fasting conditions. A total of 18 and 30 healthy volunteers were enrolled in IN 11 005 and IN 14 001, respectively.
In study IN 11 005, AP-CD/LD produced more consistent mean LD plasma concentrations overtime, with attenuated peak-trough differences compared with IR-CD/LD. The mean plasma concentration of CD was similar between IR-CD/LD and AP-CD/LD. Apparent half-life was increased from 1.8 hours with IR-CD/LD to 5.2 hours with AP-CD/LD, while peak plasma concentration (Cmax) was decreased from 4,062 ng/mL to 1,951 ng/mL.
LD plasma Cmax concentrations were similar in study IN 14 001, following either a low/medium calorie or high-calorie meal; under fasting conditions, more variability was seen, including significantly shorter retention time versus either fed condition. Likewise, mean CD plasma Cmax concentrations were comparable between the low/medium and high-calorie meals, but significantly greater at nearly all collection times with fasting.
“These data are supportive of our clinical development program for AP-CD/LD and demonstrated that our technology provided more consistent LD plasma levels and less peak trough fluctuation when compared to IRCD/LD. In addition, these data suggest that AP-CD/LD should be taken with meals, which is consistent with the current dosing regimen in our ongoing Phase 3 clinical trial of AP-CD/LD to treat advanced Parkinson's disease patients,” said Dr. Gendreau. “The poster generated considerable interest among neurologists in attendance, which is key to enhancing awareness of our AP-CD/LD, as we expect to complete enrollment of the Phase 3 program later this year.”