Healhty
Conditions
Keywords
multiple-dose, open-label, pharmacokinetic
Brief summary
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.
Detailed description
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.
Interventions
DRUGCarbidopa and Levodopa Controlled-Release Tablets (25 mg/150 mg)
Administered twice daily for one day with a 5-hour interval between doses.
Sponsors
Shanghai WD Pharmaceutical Co., Ltd.
Shanghai Xuhui Central Hospital
BalGenSource Medical Technology Co. Ltd.
Shanghai Xihua Scientific Co., Ltd.
Shanghai BioGuider Medical Technology Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult male or female participants aged 18 to 55 years (inclusive) at the time of signing the informed consent form (ICF). * Body weight: male ≥ 50 kg, female ≥ 45 kg; body mass index (BMI) between 18 and 27 kg/m² (inclusive) (BMI = weight \[kg\] / height² \[m²\]). * Medical history inquiry, physical examination, vital signs, laboratory tests (complete blood count, urinalysis, blood biochemistry, serological virology tests, coagulation function), 12-lead ECG, intraocular pressure measurement, abdominal ultrasound, and chest X-ray during the screening period are all within normal ranges or clinically insignificant if outside normal ranges. * Participants (including their spouses or partners) have no plans for conception or for donating sperm/eggs from the time of signing the ICF (for females)/first dosing (for males) until 3 months after the last dose, and voluntarily agree to use effective non-pharmacological contraception during the trial period. * Fully understand the trial content, procedures, and potential adverse reactions, voluntarily agree to participate, and sign the ICF before any trial-related procedures begin. * Able to communicate well with the investigators and capable of understanding and complying with the requirements of this trial.
Exclusion criteria
* Allergy-prone constitution, history of allergic diseases, or known severe allergic reaction or allergy history to levodopa/carbidopa or related medications. * Drug use within 3 months prior to screening, history of drug abuse, or positive urine drug abuse screening (morphine, methamphetamine, ketamine, methylenedioxymethamphetamine, tetrahydrocannabinol acid, cocaine). * History of glaucoma, cancer, diabetes mellitus, bronchial asthma, or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, hematological, dermatological, endocrine, neuropsychiatric diseases, or other significant conditions. * Dysphagia or any condition that may affect drug absorption (e.g., gastrectomy, cholecystectomy, gastric bypass, duodenotomy, colectomy), or gastrointestinal diseases causing clinically significant symptoms such as nausea, vomiting, diarrhea, or malabsorption syndrome. * History of orthostatic hypotension. * Any relevant medical history, surgical history, or trauma within 3 months prior to the first dose that may affect trial safety or drug pharmacokinetics, or planned surgery during the trial period. * Use of prescription drugs, over-the-counter medications, health products, Chinese herbal medicines, or dietary supplements within 4 weeks prior to the first dose, especially monoamine oxidase inhibitors (e.g., phenelzine, rasagiline, selegiline, brofaromine, toloxatone, isocarboxazid, etc.). * Participation in any clinical trial and receipt of investigational drugs within 3 months prior to the first dose. * Blood donation (including component blood) or significant blood loss (≥400 mL), blood transfusion, or use of blood products within 3 months prior to the first dose. * Difficulty with venous access, unsuitability or unwillingness to use intravenous catheters, or history of needle/blood phobia. * Heavy smokers or average daily cigarette consumption of more than 10 cigarettes within 3 months prior to screening. * Alcohol consumption exceeding 21 standard units per week within 3 months prior to screening (1 standard unit contains 14g of alcohol, e.g., 360 mL of beer, 45 mL of 40% spirits, or 150 mL of wine), positive alcohol breath test, or unwillingness to abstain from alcohol from 48 hours before the first dose of each period until the completion of blood sampling for that period. * Estimated glomerular filtration rate (eGFR) \< 90 mL/min·1.73m² during the screening period. * During screening: systolic blood pressure \< 90 mmHg or ≥ 140 mmHg, diastolic blood pressure \< 60 mmHg or ≥ 90 mmHg, pulse rate \> 100 beats/min or \< 50 beats/min. * History of prolonged QT interval or other clinically significant cardiac diseases, or QTcF ≥ 450 ms on ECG during screening. * Symptoms of acute infection (e.g., influenza) or acute gastroenteritis within 2 weeks prior to screening, or history of vomiting or diarrhea within 1 week prior to screening. * Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or Treponema pallidum antibody. * Currently pregnant (including positive pregnancy test) or lactating female. * Poor compliance as judged by the investigator, or other factors deemed unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Plasma Concentration (Cmax) of Carbidopa and Levodopa | 24 hours after the first dose. | 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. |
| Area under the Concentration versus Time Curve from 0 to Time t (AUC0-t) of Carbidopa and Levodopa | 24 hours after the first dose. | 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. |
| Area under the Concentration versus Time Curve from 0 Extrapolated to Infinity (AUC0-∞) of Carbidopa and Levodopa | 24 hours after the first dose. | 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 to Maximal Plasma Concentration (tmax) of Carbidopa and Levodopa | 24 hours after the first dose. | 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. |
| Elimination Half-life (t1/2) of Carbidopa and Levodopa | 24 hours after the first dose. | 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. |
| Terminal Elimination Rate Constant (λz) of Carbidopa and Levodopa | 24 hours after the first dose. | 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. |
| Apparent Clearance (CL/F) of Carbidopa and Levodopa | 24 hours after the first dose. | 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. |
| Apparent Volume of Distribution (Vd/F) of Carbidopa and Levodopa | 24 hours after the first dose. | 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. |
| Cmax of Levodopa and Carbidopa for Each Dose | 24 hours after the first 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. |
| AUC0-τ of Levodopa and Carbidopa for Each Dose | 24 hours after the first 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. |
| Ratio of ΔC0.5 between the Two Doses | 24 hours after the first dose. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants for Each Type of Adverse Events (AEs) | Throughout the study, about 21 days. | 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. |
| Number and Percentage of Participants with Abnormal Findings in Laboratory Tests, Physical Examinations, Vital Signs and 12-lead Electrocardiogram (12-lead ECG) | Baseline, 1 week, 2 weeks and 3 weeks. | 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. |
Countries
China
Contacts
CONTACTDanyong Zhang, Master
CONTACTYan Jiao, Master
PRINCIPAL_INVESTIGATORYanmei Liu, Master
Shanghai Xuhui Central Hospital
Outcome results
None listed