Despite the absence of double-blind trials, levodopa-carbidopa intestinal gel is approved for use in 43 countries. This study aimed to assess its safety and efficacy in patients with advanced Parkinson’s disease in a 12 week prospective, double-blind, placebo-controlled setting.
The study randomised 71 patients (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo, of which 66 completed the study. The primary endpoint was change from baseline to final visit in motor off -time.
The following findings were reported from baseline to 12 weeks in the full-analysis set:
• Mean off -time decreased by 4.04 h for 35 patients allocated to the levodopa-carbidopa intestinal gel group vs. decrease of 2.14 h for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference –1.91 h; p=0.0015).
• Mean on-time without troublesome dyskinesia increased by 4.11 h in the intestinal gel group and 2.24 h in the immediate-release oral group (difference 1.86; p=0.0059).
• In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (5 [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (7 [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube.
The researchers note that the benefits found for intestinal gel delivery were of a greater magnitude than those obtained with medical therapies to date, and to their knowledge, this is the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. They acknowledge several limitations to their study such as the large number of sites with few participants; the lack of a formal assessment of masking; and the small size and short duration of the study, which precludes an assessment of the complications associated with levodopa-carbidopa intestinal gel, as well as problems that the jejunostomy tube might develop after this time period. The short duration also prevents an assessment of the potential of levodopa-carbidopa intestinal gel to reduce established dyskinesia, and to determine what level of expertise is required to manage patients who have this procedure.
Long-term studies will be needed to determine whether continuous levodopa infusion reduces dyskinesia in addition to off -time. In addition, head-to-head comparisons are needed versus the two main alternatives for management of severe problems with refractory off -time complications: continuous subcutaneous apomorphine infusion and functional surgery.
Currently levodopa-carbidopa intestinal gel is not routinely funded for use in Parkinson’s disease in NHS England.