A possible cause of motor fluctuations in patients with Parkinson disease is the erratic drug absorption. In a randomized double-blind double-dummy study of melevodopa (levodopa methyl ester), a highly soluble levodopa pro-drug plus carbidopa (CHF 1512) was compared to a standard formulation of levodopa/carbidopa (LD/CD) in 74 fluctuating Parkinson disease patients. The first afternoon, LD/CD tablet was substituted with an equimolar dose of CHF 1512. The study lasted 4 weeks and was followed by an 8-week (optional) open phase. The primary efficacy variable was latency to "on." Patients randomized to receive CHF 1512 had a significative shorter latency to "on" than those randomized to LD/CD and a similar "on" duration. The safety profile of CHF 1512 was also comparable with LD/CD.