Carbidopa and Levodopa Extended Release Capsules in Patients with and without Troublesome and Non-Troublesome Dyskinesia

J Parkinsons Dis. 2020;10(3):915-925. doi: 10.3233/JPD-202010.


Background: Carbidopa (CD) and levodopa (LD) extended release (CD-LD ER) capsules are designed to combine both immediate and extended release pharmacokinetics. In the phase 3, randomized, double-blind, ADVANCE-PD trial, patients randomized to CD-LD ER experienced a 1.17-hour greater reduction in OFF time compared to patients randomized to CD-LD IR (p < 0.0001).

Objective: To compare CD-LD IR optimization to CD-LD ER conversion based on patient dyskinesia status at baseline using data from the ADVANCE-PD trial.

Methods: This was a retrospective analysis of the ADVANCE-PD study. Patients were categorized by dyskinesia status at baseline into 1) those who had No Dyskinesia (ND), 2) those who had Non-Troublesome Dyskinesia Only (NTDO), and 3) those who had Troublesome Dyskinesia (TD).

Results: Comparative reductions in OFF time favoring CD-LD ER over CD-LD IR were similar for the ND (-1.08 h, p = 0.0071, n = 183) and NTDO (-1.12 h, p = 0.0104, n = 131) groups, and smaller for the TD group (-0.82 h, p = 0.2382, n = 79). Reductions in OFF time for both CD-LD ER conversion and CD-LD IR adjustment were largest within the ND group and smallest within the TD group (CD-LD ER: ND -2.86 h, NTDO -2.11 h, TD -1.36 h; CD-LD IR: ND -1.78 h, NTDO -0.99 h, TD -0.55 h).

Conclusion: Responses to both CD-LD IR adjustment and CD-LD ER conversion depended on baseline dyskinesia status. Significant reductions in OFF time with CD-LD ER compared to CD-LD IR were observed in the ND and NTDO groups. In the TD group, comparing CD-LD ER conversion to CD-LD IR optimization, benefits were still observed, but there was less reduction in OFF time, less reduction in troublesome dyskinesia, and fewer patients self-rated themselves much or very much improved than in the ND and NTDO groups. These data suggest that in clinical practice, the best chances for success with conversion from CD-LD IR to CD-LD ER are in patients without TD.

Keywords: Levodopa; OFF; Parkinson’s disease; dyskinesia; extended release; treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / therapeutic use*
  • Capsules / therapeutic use
  • Carbidopa / therapeutic use*
  • Delayed-Action Preparations / therapeutic use
  • Drug Administration Schedule
  • Drug Combinations
  • Dyskinesias / drug therapy*
  • Female
  • Humans
  • Levodopa / therapeutic use*
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*


  • Antiparkinson Agents
  • Capsules
  • Delayed-Action Preparations
  • Drug Combinations
  • carbidopa, levodopa drug combination
  • Levodopa
  • Carbidopa