Final Visit Completed for Last Patient in Phase 3 Trial Testing Accordion Pill
The last Parkinson’s patient enrolled in Intec Pharma’s Phase 3 ACCORDANCE clinical trial has completed the final required visit, the company announced.
Taking place at approximately 90 clinical sites throughout the United States, Europe, and Israel, the trial (NCT02605434) was designed to test the safety and efficacy of the Accordion Pill-Carbidopa/Levodopa (AP-CD/LD) compared with immediate release Sinemet, an approved combination of levodopa and carbidopa marketed by Merck, and with placebo in the treatment of advanced Parkinson’s disease.
“We are excited to announce that the last patient’s last visit has taken place as it is an important milestone in the development of our Accordion Pill platform. Completion of the ACCORDANCE study brings us closer to potentially providing an enhanced baseline levodopa treatment to advanced [Parkinson’s disease] patients,” R. Michael Gendreau, MD, PhD, chief medical officer of Intec Pharma, said in a press release.
The Accordion Pill is an innovative drug delivery system that helps release the commonly used Parkinson’s therapy carbidopa/levodopa slowly in the stomach over hours. This new system allows the therapy to be released in both immediate- and controlled-release modes.
Controlled release enables a slow discharge of the therapy in the stomach over eight to 12 hours, potentially allowing for more steady absorption in the upper gastrointestinal tract, where levodopa is absorbed.
“By delivering more uniform levodopa plasma concentrations than those provided by currently available orally-administered levodopa products, we expect to improve the duration and consistency of symptom relief provided by levodopa. Assuming successful ACCORDANCE study outcomes, we believe the AP-CD/LD will result in improved motor fluctuation control, reduced symptomology, a simpler dosing regimen and enhanced compliance,” Gendreau said.
Prior to the 13-week randomized part of the study, 462 patients were first stabilized and optimized on Sinemet and then on AP-CD/LD during two open-label periods lasting six weeks.
Then, 320 of these patients were randomized to receive either an AP-CD/LD capsule — containing 50 mg of carbidopa with 400 or 500 mg of levodopa — two or three times a day and a matching Sinemet placebo. Or they were given an immediate-release Sinemet tablet — consisting of 25 mg of carbidopa and 100 mg of levodopa — and a matching AP-CD/LD placebo at least four times a day.
The study’s primary goal is the reduction in the percentage of daily “off” time during waking hours (based on patients’ home diaries), which will be considered statistically significant if it leads to at least a one-hour difference between Sinemet and AP-CD/LD. Off time refers to motor fluctuations when levodopa wears off and Parkinson’s symptoms return.
Secondary goals include the reduction of involuntary movements during “on” periods, and improvement in Clinical Global Impression Scale-Improvement (CGI-I) scores — as recorded by the physician and patient — and the Unified Parkinson’s Disease Rating Scale (UPDRS), which assesses both motor and non-motor symptoms.
To date, a preliminary analysis of the initial clinical data shows that the average age of participants at study enrollment was 63 years (66% males); patients have had a diagnosis of Parkinson’s for an average of 8.7 years; and the average daily off time for the group given Sinemet was approximately five hours.
All participants completing the 13-week randomized period were eligible to enter an open-label extension study where they all receive AP-CD/LD for an additional 12 months. More than 90% of eligible patients have chosen to continue in the extension study.
Clinical data and patient diaries are in the process of being validated, and results are expected to be announced this summer.
“With topline results expected this summer, we are actively making plans for our regulatory submissions. Toward that end, we are encouraged that more than 90% of eligible patients elected to enroll in the AP-CD/LD long-term open-label extension (OLE) study as these data will provide the long-term safety required as part of the registration package. In addition, we have made significant progress with our commercial scale manufacturing plans and expect to initiate the validation, bridging and stability studies in the coming months,” said Jeffrey A. Meckler, CEO of Intec Pharma.
“We look forward to receiving the results from the ACCORDANCE trial and, if successful, having them confirm that treatment with AP-CD/LD reduces motor complications in advanced PD patients in comparison to treatment with standard oral levodopa,” he added.