WD-1603 contains two different drugs called levodopa and carbidopa in one tablet. The goal of this clinical trial is to see if taking the study drug WD-1603 at different time intervals affects how the drug acts in healthy volunteers. We also want to learn about the safety of WD-1603. The main question we want to answer is: * How does the body process WD-1603 when it is taken by different time intervals? What will participants do? * Participants will take one tablet of WD-1603 twice a day on three separate days. * On each dosing day, the two doses will be spaced different hours apart. * Between each dosing day, there will be a rest period of up to 7 days.
This trial is a multiple-dose, open-label, sequential, three-period pharmacokinetic study comparing different dosing intervals of WD-1603 in healthy participants. The purpose of the study is: * To evaluate the effect of different dosing intervals on the pharmacokinetics of twice-daily WD-1603 when administered before meals. * To assess the safety and tolerability of WD-1603 in healthy participants. Each participant will receive the investigational drug in the sequence of Treatment A, Treatment B, and Treatment C. After each dosing period, there will be a washout period of up to 7 days. This Phase I clinical trial is planned to enroll 12 healthy participants, with an appropriate proportion of female participants (at least one quarter, i.e., 3 participants). Pharmacokinetic parameters will be calculated using Phoenix WinNonlin (version 8.3 or higher), and other analyses will be performed using SAS software (version 9.4 or higher). Using PKS, an analysis of variance (ANOVA) is performed on the natural log-transformed Cmax, AUC0-τ, and ΔC0.5. The model includes dosing occasion as a fixed effect and participant as a random effect. The 90% confidence interval for the geometric mean ratio (second dose/first dose) of each parameter is calculated.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Administered twice daily for one day with a 5-hour interval between doses.
Administered twice daily for one day with a 6-hour interval between doses.
Administered twice daily for one day with a 7-hour interval between doses.
Shanghai Xuhui Central Hospital
Shanghai, China
RECRUITINGMaximal Plasma Concentration (Cmax) of Carbidopa and Levodopa
Maximal plasma concentration (Cmax) of carbidopa and levodopa after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
Area under the Concentration versus Time Curve from 0 to Time t (AUC0-t) of Carbidopa and Levodopa
Area under the concentration versus time curve from 0 to time t (AUC0-t) of carbidopa and levodopa after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
Area under the Concentration versus Time Curve from 0 Extrapolated to Infinity (AUC0-∞) of Carbidopa and Levodopa
Area under the concentration versus time curve from 0 extrapolated to infinity (AUC0-∞) of carbidopa and levodopa after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
Time to Maximal Plasma Concentration (tmax) of Carbidopa and Levodopa
Time to maximal plasma concentration (tmax) of carbidopa and levodopa after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
Elimination Half-life (t1/2) of Carbidopa and Levodopa
Elimination half-life (t1/2) of carbidopa and levodopa after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
Terminal Elimination Rate Constant (λz) of Carbidopa and Levodopa
Terminal elimination rate constant (λz) of carbidopa and levodopa after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
Apparent Clearance (CL/F) of Carbidopa and Levodopa
Apparent clearance (CL/F) of carbidopa and levodopa after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
Apparent Volume of Distribution (Vd/F) of Carbidopa and Levodopa
Apparent volume of distribution (Vd/F) of carbidopa and levodopa after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
Cmax of Levodopa and Carbidopa for Each Dose
Cmax of carbidopa and levodopa for each dose after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants.
Time frame: 24 hours after the first dose.
AUC0-τ of Levodopa and Carbidopa for Each Dose
AUC0-τ of carbidopa and levodopa for each dose after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants, where τ is the dosing interval.
Time frame: 24 hours after the first dose.
Ratio of ΔC0.5 between the Two Doses
Ratio of ΔC0.5 of carbidopa and levodopa between the two doses after two doses of WD-1603 administered orally before meals at different dosing intervals in healthy participants, where the ΔC0.5 of the first dose is equal to the concetration at 0.5 hour C0.5; the ΔC0.5 of the second dose is the difference between the concontration at t+0.5 hours (Ct+0.5) and the concentration at t (Ct) (t is the dosing interval).
Time frame: 24 hours after the first dose.
Number and Percentage of Participants for Each Type of Adverse Events (AEs)
All AEs will be coded using MedDRA version 28.1 or higher to provide the System Organ Class (SOC) and Primary Term (PT) for each event. AEs will be summarized by treatment period, including the number and percentage of participants for each event category and for treatment-related adverse events. Additionally, summarize treatment-emergent adverse events (TEAEs) by treatment period for deaths, serious adverse events (SAEs), events leading to discontinuation of study medication, and events leading to early termination of the study.
Time frame: Throughout the study, about 21 days.
Number and Percentage of Participants with Abnormal Findings in Laboratory Tests, Physical Examinations, Vital Signs and 12-lead Electrocardiogram (12-lead ECG)
Summarize measurements recorded at each time point (screening, baseline, each visit, and study completion) along with changes from baseline at each visit and study completion. Use cross-tabulation to summarize baseline values for each indicator and the most clinically significant change determined post-treatment.
Time frame: Baseline, 1 week, 2 weeks and 3 weeks.
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