A Study of the Efficacy and Safety of Carbidopa-Levodopa Extended-Release Tablets in Patients With Parkinson's Disease

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) assesses Parkinson's disease impairment. Part II (Motor Experiences of Daily Living) has 13 items; Part III (Motor Examination) has 33 scores from 18 items. Each item is rated 0-4 (0=normal, 1=slight, 2=mild, 3=moderate, 4=severe). Part II total 0-52; Part III total 0-132. Higher scores on both parts indicate greater severity. Combined score = sum of Part II and III totals, range 0-184; higher = worse motor impairment. Change from baseline = Day 14 score minus baseline. Change scores range -184 to +184; negative = improvement, positive = worsening.

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II (Motor Experiences of Daily Living) is a 13-item scale used to assess motor experiences of daily living in Parkinson's disease. Each item is rated on a 0-4 scale (0 = normal, 1 = slight, 2 = mild, 3 = moderate, 4 = severe). The Part II total score ranges from 0 to 52. Higher scores indicate more severe impairment in motor experiences of daily living (worse outcome). Change from baseline is calculated separately for Day 14 and Day 27 as the score at each time point minus the baseline score. Change scores range from -52 to +52. A negative change indicates improvement, while a positive change indicates worsening.

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) contains 33 scores based on 18 items and is used to assess motor impairment in Parkinson's disease. Each item is rated on a 0-4 scale (0 = normal, 1 = slight, 2 = mild, 3 = moderate, 4 = severe). The Part III total score ranges from 0 to 132. Higher scores indicate more severe motor impairment (worse outcome). Change from baseline is calculated separately for Day 14 and Day 27 as the score at each time point minus the baseline score. Change scores range from -132 to +132. A negative change indicates improvement in motor impairment, while a positive change indicates worsening.

Cmax (Maximum Plasma Concentration) of Levodopa and Carbidopa Following WD-1603 Administration.

Cmin (Minimum Plasma Concentration) of Levodopa and Carbidopa Following WD-1603 Administration.

Plasma concentrations of levodopa and carbidopa were measured on Day 28 at pre-dose (0 hour) and 0.5, 1, 2, 3, 4, 5, 6, and 9 hours after the second dose. The area under the plasma concentration-time curve from time 0 to τ (AUC0-τ) was calculated using the linear trapezoidal method, where τ is the dosing interval of 5 hours. The area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) was calculated as AUC0-t + Clast/λz, where AUC0-t is the AUC from time 0 to the last measurable concentration (Clast), and λz is the terminal elimination rate constant. AUC values are presented in ng*h/mL for both levodopa and carbidopa. Higher AUC values indicate greater systemic exposure.

Plasma levodopa concentrations were measured on Day 28 at pre-dose (0 hour) and 0.5, 1, 2, 3, 4, 5, 6, and 9 hours after the second dose. The fluctuation index was calculated as (Cmax - Cmin) / Cavg, where Cmax is the maximum plasma concentration, Cmin is the minimum plasma concentration, and Cavg is the average plasma concentration calculated as AUC0-τ / τ, with τ = 5 hours. A higher fluctuation index indicates greater fluctuation in plasma levodopa concentration.

Adverse events (AEs) refer to any untoward medical occurrence in participants, which may present as symptoms and signs, diseases, or abnormal laboratory findings, and may not necessarily have a causal relationship with the study drug. An event was recorded as an AE if at least one of the following criteria was met: (1) accompanying symptoms and signs; (2) examination results requiring treatment measures (such as surgical intervention); or (3) examination results leading to changes in the dosing schedule of the study drug (such as dose change, dosing delay, or discontinuation). The number and percentage of participants with AEs are reported.

BDI-II scores are collected for safety assessment. BDI-II is a 21-item self-administered survey which is scored on a scale of 0-3 in a list of four statements arranged in increasing severity about a particular symptom of depression. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.