title: Long-term safety and maintenance of efficacy of levodopa-carbidopa intestinal gel: an open-label extension of the double-blind pivotal study in advanced Parkinson's disease patients.
abstract: BACKGROUND
  Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously via intrajejunal percutaneous gastrostomy tube.
  
  
  OBJECTIVE
  To examine long-term safety, efficacy and quality of life of LCIG in an open-label extension study.
  
  
  METHODS
  Patients received 52 weeks of open-label LCIG treatment following a 12-week double-blind, double-dummy trial in which they were randomized to either LCIG or immediate-release oral levodopa-carbidopa. Patient cohort designation was by receipt of LCIG in the preceding trial randomization (continuing-LCIG vs. LCIG-naïve patients).
  
  
  RESULTS
  Sixty-two of 66 subjects in the double-blind proceeded to the open-label extension. Most subjects (95%) reported ≥1 adverse event (AE); only 3 subjects (4.8%) discontinued due to AEs. AE incidence declined gradually over 52 weeks. Serious AEs were reported by 23%. LCIG-naïve patients (N = 29) showed a decrease in "Off" time and an increase in "On" time without troublesome dyskinesia (change from baseline to final visit in mean [SD] hours = -2.34 [2.78] P < 0.001 and 2.19 [3.70] P = 0.005, respectively), while continuing-LCIG patients (N = 33) showed sustained "Off" time duration and further improvement in "On" time without troublesome dyskinesia (-0.42 [2.67] P = 0.377 and 1.00 [2.58] P = 0.036, respectively). The majority of patients in both groups (LCIG-naïve, continuing-LCIG, respectively) were rated 'Much Improved' or 'Very Much Improved' at final visit on the Clinical Global Impression-Improvement scale (69.0%, 69.7%).
  
  
  CONCLUSIONS
  Continuing-LCIG patients continued to derive benefit from LCIG while the magnitude of improvement among LCIG-naïve patients was similar to that observed for patients on LCIG in the preceding double-blind study. The overall AE profile was consistent with previous phase 3 clinical trials involving the LCIG system.
authors.affiliation: University of Kentucky Medical Center, Lexington, KY, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Slevin
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Fernandez
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Zadikoff
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Coleen
authors.initials: C
authors.lastname: Hall
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Eaton
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Dubow
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Krai
authors.initials: K
authors.lastname: Chatamra
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Benesh
mesh_terms: D000367:Age Factors; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002230:Carbidopa / Q000627:therapeutic use*; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels / Q000627:therapeutic use; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D005782:Gels; D007980:Levodopa; D002230:Carbidopa
keywords: Parkinson's disease; clinical trial; levodopa-carbidopa intestinal gel; motor fluctuations; percutaneous endoscopic gastrostomy