Objective: The objective of this study was to evaluate the safety, pharmacokinetic profile, and efficacy of ONO-2160/carbidopa (CD) and to compare them with an immediate-release formulation of levodopa/CD in patients with Parkinson’s disease.

Background: ONO-2160 is an orally-available levodopa prodrug that is passively absorbed throughout the gastrointestinal tract and then rapidly converted to levodopa by esterases. ONO-2160/CD tablet was developed to ameliorate pharmacokinetic limitations of levodopa in Ono Pharmacutical Co.,Ltd, and has been shown to reduce variability in plasma levodopa concentration in rat.

Methods: We performed a single-center, open-label study in 2 groups of 6 patients each with Parkinson’s disease experiencing motor fluctuations on levodopa therapy. Maximum dose of ONO-2160/CD in the first and second group was 600/50 mg and 900/75 mg for 3 times/day, respectively. Patients were treated with levodopa/CD (dosing frequency: 3 to 7 times/day) for 3 days followed by ONO-2160/CD for 7 days. Pharmacokinetic assessments were undertaken on day 3 levodopa/CD treatment and on day 1 and 7 ONO-2160/CD treatment. In order to evaluate motor function, Unified Parkinson’s disease Rating Scale (UPDRS) Part 3 was undertaken at predose and every hour for 10 hours on day 2 levodopa/CD treatment and on day 6 ONO-2160/CD treatment.

Results: Multiple dose data showed ONO-2160/CD was safe, well tolerated, and substantially reduced variability in plasma levodopa concentrations in both groups. The improvement in UPDRS Part 3 score was better at predose and during ONO-2160/CD treatment than levodopa/CD treatment in the second group.

Conclusions: This study indicates that ONO-2160/CD provides more sustained plasma levodopa concentrations than levodopa/CD with a lower peak to trough fluctuation index. ONO-2160/CD administered 3 times daily ameliorated total score of UPDRS Part 3 for 10 hours, suggesting an advantage for this novel prodrug of levodopa. The prolonged stable plasma concentrations with ONO-2160 treatment were associated with improved UPDRS Part 3 total score. The results of this study of PD patients support the potential of ONO-2160/CD to reduce motor fluctuations without increasing dyskinesias, as compared to levodopa/CD treatment.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-pharmacokinetics-and-efficacy-of-levodopa-prodrug-ono-2160cd-a-study-in-patients-with-parkinsons-disease/