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Randomized Controlled Trial
. 2019 Apr;7(2):e00473.
doi: 10.1002/prp2.473.

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

Matthew Rosebraugh  1 , Hari V Kalluri  1 , Wei Liu  1 , Charles Locke  1 , Dilraj Sidhu  1 , Jian-Hwa Han  1 , Janet Benesh  1
Affiliations
Randomized Controlled Trial

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

Matthew Rosebraugh et al. Pharmacol Res Perspect. 2019 Apr.

Abstract

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 Cmax geometric mean for the LCIG-HV formulation was 4% higher than that of the LCIG-LV formulation. PEs of levodopa AUCt and AUCinf geometric means were comparable for both formulations. PEs of carbidopa Cmax , AUCt and AUCinf geometric means for the LCIG-HV formulation were 3%-5% higher than those of the LCIG-LV formulation. For both formulations, the median Tmax 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. Cmax , AUCt and AUCinf 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.

Keywords: bioequivalent; carbidopa; intestinal gel; levodopa.

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Conflict of interest statement

All authors are employees of AbbVie and may hold AbbVie stock or stock options.

Figures

Figure 1
Figure 1
Levodopa dissolution profiles for LCIG‐LV commercial and LCIG‐HV formulations
Figure 2
Figure 2
Carbidopa dissolution profiles for LCIG‐LV commercial and LCIG‐HV formulations
Figure 3
Figure 3
Comparison of levodopa and carbidopa pharmacokinetics between the LCIG‐HV formulation and the LCIG‐LV commercial formulation. PK profiles were normalized by dose delivered
See this image and copyright information in PMC

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