Intec Pharma has reported top-line results from the Phase III ACCORDANCE clinical trial of its Accordion Pill-Carbidopa/Levodopa (AP-CD/LD) to treat the symptoms of advanced Parkinson’s disease (PD).
The trial failed to meet the primary endpoint, with no statistical superiority of the investigational therapy in reducing daily OFF time compared to Sinemet (immediate release CD/LD).
Safety analysis showed that treatment-emergent adverse effects (TEAEs) with AP-CD/LD were generally consistent with the established profile of CD/LD formulations, without any new safety issues.
Widely used as a symptomatic therapy for Parkinson’s, levodopa is associated with motor complications such as OFF periods and dyskinesia.
AP-CD/LD is a gastric-retentive drug delivery system with immediate and extended-release of carbidopa and levodopa. Extended-release of levodopa over 8-12 hours is expected to allow the steady absorption of active ingredients.
The multi-centre, global, randomised, double-blind, active-controlled, parallel-group, double-dummy ACCORDANCE trial assessed the safety and efficacy of the therapy at more than 90 sites in the US, Europe, and Israel.
It initially involved two six-week open-label periods, where participants were stabilised and then optimised on Sinemet and subsequently on AP-CD/LD. This was followed by a 13-week randomised, double-blinded portion.
Of the 462 subjects enrolled in the Sinemet titration period, 320 were randomised into the double-blinded portion.
Subjects completing the double-blinded period were eligible for an open-label extension study that provided AP-CD/LD therapy for an additional 12 months.
The primary efficacy endpoint was the change in the percent of daily OFF time during waking hours from baseline to endpoint. A one-hour difference in OFF time was observed between Sinemet and AP-CD/LD, which failed to demonstrate statistical significance.
AP-CD/LD also failed to reach the trial’s secondary endpoints, including a change in ON time without troublesome dyskinesia during waking hours from baseline to endpoint, CGI-I at endpoint, and change in the Unified Parkinson’s Disease Rating Scale (UPDRS) score parts II and III.
Intec Pharma vice-chairman and CEO Jeffrey Meckler said: “We are disappointed that the ACCORDANCE study didn’t meet its target endpoints with statistical significance.
“While the data suggests that the AP CD/LD did achieve an acceptable safety profile and did treat Parkinson’s disease symptoms, it did not achieve a statistically significant superiority to standard immediate-release levodopa therapy.”