Efficacy and safety of levodopa-carbidopa intestinal gel from a study in Japanese, Taiwanese, and Korean advanced Parkinson's disease patients

Abstract

In a previous multinational, randomized, double-blind, double-dummy study, levodopa-carbidopa intestinal gel (LCIG) was tolerable and significantly improved 'off' time in advanced Parkinson's disease (PD) patients. However, efficacy and safety in the Asian population has not yet been demonstrated. In this open-label study, efficacy and safety of LCIG were assessed in Japanese, Korean, and Taiwanese advanced PD patients with motor complications not adequately controlled by available PD medication. The patients were treated with LCIG monotherapy for 12 weeks. The primary end point was the mean change from baseline to week 12 in 'off' time, as reported in the PD Symptom Diary, normalized to a 16 h waking day and analyzed by a mixed-model repeated-measures analysis. Adverse events (AEs) were recorded. Thirty-one patients were enrolled (23 Japanese, 4 Taiwanese, 4 Korean) and 28 (90%) completed the study. For those who completed the study, the mean (s.d.) total daily levodopa dose from LCIG was 1,206.3 (493.6) mg/day at final visit (n=28); last observation carried forward (n=30) was 1,227.6 (482.8) mg/day. There was a significant mean change (s.d.) of -4.6 (3.0) hours of 'off' time from baseline (mean (s.d.)=7.4 (2.3)) to week 12 (n=29), P<0.001. All the patients had an AE, with the most frequently reported being incision site pain (42%); 1 (3.2%) discontinued treatment because of an AE and later died because of sepsis, which the investigator considered unrelated to LCIG treatment. These results suggest that LCIG is efficacious and tolerable in Japanese, Taiwanese, and Korean advanced PD patients.

Figure 1

(a) Patient disposition and (b) study design. The NJ period was expected to be 5 days, but could vary. Patients who prematurely discontinued the study and did not continue into the separate extension study had a follow-up visit 7 days after discontinuation. NJ, nasojejunum; PEG-J, percutaneous endoscopic gastronomy-jejunum.

Figure 2

Mean daily hours of ‘off’ time at baseline and final visit in (a) all patients and ethnic subgroups and (b) age and gender subgroups. Daily totals were normalized to a 16 h waking day and the 3 days before the visit were averaged. Error bars indicate standard deviation. P values from a two-sided one-sample t-test indicate statistically significant mean change from baseline of *P⩽0.05, **P⩽0.01, and ***P⩽0.001.

Figure 3

Change from baseline for PD diary measures. Daily totals were normalized to a 16 h waking day and the 3 days before the visit were averaged. ‘On’ time without troublesome dyskinesia is the sum of ‘on’ time without dyskinesia and ‘on’ time with non-troublesome dyskinesia. At baseline, the mean (s.d.) daily hours of PD Symptom Diary measures were: ‘off’ time=7.4 (2.3), ‘on’ time with TSD=1.1 (2.3), and ‘on’ time without TSD=7.5 (2.5). Error bars indicate standard error. P values indicate statistically significant mean change from baseline of *P⩽0.05 and ***P⩽0.001. At baseline, weeks 1–6, and final, the sample size was 29; and at week 8, it was 27 for all the measures. At weeks 10 and 12, the sample size was 28 for ‘on’ time with and without TSD and 27 for ‘off’ time. PD, Parkinson's disease; TSD, troublesome dyskinesia.

Figure 4

Mean PDQ-39 domain scores at baseline and final visit. N=30. Error bars indicate standard deviation. P values from a two-sided one-sample t-test indicate statistically significant mean change from baseline; ***P⩽0.001, ^aP=0.059, ^bP=0.070. PDQ, Parkinson’s Disease Questionnaire.