Objective: To determine gastric retention (GR) of the Accordion Pill™ (AP) in patients with Parkinson’s disease (PD) and healthy volunteers.

Background: While carbidopa/levodopa (CD/LD) is the gold standard treatment for PD, patients experience progressive motor fluctuations with ongoing treatment. Retaining the dosage form that contains LD in the stomach and gradually release the drug, may facilitate prolonged absorption, improving efficacy and safety while reducing daily dosing. AP-CD/LD is a novel drug delivery system based on GR of multilayer films containing immediate-release CD and both immediate- and controlled-release LD.

Methods: In an open label, randomized, 3-way crossover study (IN-08-004), patients with PD (18–75 y) received the AP following their regular morning PD treatment. Three mechanically unique APs (weak, semi-weak, strong), containing iron oxide, were administered on test days with ≥48 h washout. All meals were standardized, and magnetic resonance imaging (MRI) was conducted post-dose at 3, 5, 7, 9, 11, and 13 hours. In a second open label study, healthy volunteers received the AP following an overnight fast; sequential MRIs were conducted every 1 h for 11 h, with breakfast and lunch standardized. Safety was assessed via adverse event (AE) monitoring.

Results: Of 18 patients enrolled, 83.3% were male and mean (SD) PD duration was 8.9 (4.6) y. Mean GR was 11.8 (7.3), 13.5 (5.8), and 13.9 (6.5) h for weak, semi-weak, and strong AP. In 11 healthy volunteers, the AP remained in the stomach for 8, 9, and 11 h in 100%, 91%, and 73% of participants. One serious AE (IN-08-004: general weakness/worsening of PD) was reported; no serious AEs were reported in healthy volunteers. Mild AEs of headache, nausea, and vomiting were reported in one participant and pain during MRI in another; all resolved.

Conclusions: AP GR was approximately 12 h in PD patients and 8 to 11 h in healthy volunteers. AP-CD/LD formulations were developed based on these demonstrated GR properties. AP-CD/LD, currently in phase 3 development for PD, may improve efficacy and safety of treatment with LD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gastric-retention-of-the-accordion-pill-results-from-mri-studies-with-parkinsons-disease-patients-and-healthy-volunteers/