To Örebro University

Objective: The aim of this study was to characterize the levodopa and carbidopa plasma concentration in relation to blinded motor function ratings. This is a part of a study where a Multimodal motor Symptoms Quantification (MuSyQ) platform consisting of three different types of sensors were tested while evoking motor fluctuations with levodopa/car-bidopa (LD/CD) microtablets in fluctuating Parkinson’s disease (PD) patients.

Background: Today, dose titration and chronic treatment largely relies on the patient’s subjective assessment of symptoms and clinicians’ assessment of patient status during a visit at the clinic.

Methods: This was a single-center, open-label, single dose study in patients experiencing motor fluctuations. Patients were given 150% of their individual levodopa equivalent morning dose. Blood sampling and motor function testing were conducted for up to 6.5 hours at prepecified time points. The patients performed standardized motor activities for clinical rating in accordance with parts of the Unified Parkinson’s disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS). Each test cycle was video recorded, and the video sequences were presented to three movement disorder specialists in a randomized order for blinded rating of UPDRS items and the treatment response scale (TRS). Concentration versus time profiles and the pharmacokinetics were compared with a study previously conducted in healthy subjects.

Results: Nineteen patients, 14 male and 5 female, were included in the study. The individual LD/CD doses ranged between 110/27.5 mg to 410/102.5 mg. The concentration time profiles are similar to the LD/CD microtablet profiles reported in healthy subjects. The blinded video ratings managed to capture the most distinctive movements.

Conclusions: This is the first pharmacokinetic study where patients received LD/CD microtablets. For patients fluctuating from ‘off’ to dyskinetic, the relationship between the plasma concentration and motor function was clearer compared to the patients that fluctuated to a lesser extent.