Levodopa‐carbidopa intestinal gel high concentration formulation is clinically bioequivalent to commercial formulation

A new levodopa‐carbidopa intestinal gel (LCIG) system featuring a higher levodopa/carbidopa (LD/CD) concentration and viscosity, LCIG‐HV, is being developed to reduce the intrajejunal volume of LD/CD that is administered as compared to the current commercial formulation, LCIG‐LV. This study characterizes the LCIG‐HV formulation and compares it to the LCIG‐LV formulation via dissolution testing and a clinical pharmacokinetic bioequivalence study. In vitro release profiles of LD/CD were determined using a USP Dissolution Apparatus 2 with 500 mL of phosphate buffer (pH 4.5) operating at 25 RPM. A single dose, open‐label study was conducted according to a two‐period, randomized, crossover design in 28 healthy subjects. The point estimate (PE) of the levodopa C max geometric mean for the LCIG‐HV formulation was 4% higher than that of the LCIG‐LV formulation. PEs of levodopa AUC t and AUC inf geometric means were comparable for both formulations. PEs of carbidopa C max, AUC t and AUC inf geometric means for the LCIG‐HV formulation were 3%‐5% higher than those of the LCIG‐LV formulation. For both formulations, the median T max for levodopa was 1.0 and 3.0 hours for carbidopa. The levodopa half‐life harmonic mean was 1.6 hour for both formulations. The carbidopa half‐life harmonic mean was 1.9 and 2.0 hour, respectively, for the LCIG‐HV and LCIG‐LV formulations. C max, AUC t and AUC inf of LD/CD carbidopa were comparable for both formulations. The current study demonstrates that the LCIG‐LV and LCIG‐HV formulations are clinically bioequivalent for LD/CD according to FDA guidance. However, the dissolution method was over discriminatory of formulation differences