Gastroretentive carbidopa/levodopa, DM‐1992, for the treatment of advanced Parkinson's disease

Objectives This study was undertaken to compare efficacy, tolerability, and pharmacokinetics of DM‐1992, an extended‐release formulation of carbidopa/levodopa (CD/ l ‐dopa) with immediate‐release (IR) CD/ l ‐dopa in patients with advanced Parkinson's disease. Methods This randomized, open‐label, crossover study included a 3‐d baseline and two 10‐d treatment periods. Patients with daily OFF time of 2.5 h or more taking 400 mg or more l ‐dopa/d in four or more divided doses were titrated to stable regimens of DM‐1992 2 times per day or CD/ l ‐dopa IR 3 times to 8 times per day. Patients were allowed to take rescue CD/ l ‐dopa as needed. Using home diaries, patients recorded OFF time and ON time with or without troublesome dyskinesia during baseline and treatment days 7 through 9. During 12‐h clinic visits on day 10, plasma samples were collected for pharmacokinetics, and motor performance was assessed hourly. Results Thirty‐four patients were enrolled; mean baseline l ‐dopa dosage was 968 mg/d. After titration, CD/ l ‐dopa IR was dosed 4.8 times per day and DM‐1992, 2 times per day. Rescue CD/ l ‐dopa IR was given 1.3 times during the DM‐1992 arm and 0.2 times during the CD/ l ‐dopa IR arm. The reduction from baseline in % OFF time was greater for DM‐1992 compared with CD/ l ‐dopa IR (−5.52% vs. +1.33%; P  = 0.0471). At steady‐state, compared with CD/ l ‐dopa IR, DM‐1992 exhibited a smoother plasma l ‐dopa concentration profile mostly because of a significantly higher (day 10) predose l ‐dopa concentration, associated with enhanced motor performance. Although more patients taking DM‐1992 had one or more adverse events (AEs) than CD/ l ‐dopa IR patients (35% vs. 15%), no pattern to the AEs was seen, nor any resulting discontinuations. Conclusions DM‐1992 was associated with a reduction in %OFF time compared with CD/ l ‐dopa IR despite a reduced dosing frequency. Although the open‐label study design and the greater number of rescue doses during the DM‐1992 arm call for caution in interpreting the results, the elevated predose plasma l ‐dopa concentration (12 h after DM‐1992 administration) lends objective support to our findings, suggesting that phase 3 studies are warranted. © 2015 International Parkinson and Movement Disorder Society