Healthy Participants
Conditions
Keywords
DM1001, Transdermal Patch, Safety, Tolerability, Pharmacokinetics, Healthy Volunteers
Brief summary
This is a Phase 1 clinical trial to evaluate the safety, tolerability, and pharmacokinetic characteristics of the DM1001 transdermal patch in healthy Chinese participants. Eligible participants will receive DM1001 according to the clinical trial protocol. Safety, tolerability, and pharmacokinetic assessments will be conducted at prespecified time points during the study. The study is intended to provide initial information on the safety, tolerability, and pharmacokinetic characteristics of DM1001 in humans.
Detailed description
This is a Phase 1 registration drug clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic characteristics of the DM1001 transdermal patch in healthy Chinese participants. The investigational product is the DM1001 transdermal patch. The study will be conducted according to the approved clinical trial protocol. In China, the study is classified as a Class 2.2 chemical drug clinical trial. The study will evaluate the safety and tolerability of DM1001 and characterize its pharmacokinetic properties during the clinical trial. Safety, tolerability, and pharmacokinetic assessments will be performed according to the procedures and time points specified in the clinical trial protocol. The study is being conducted by the Phase I Clinical Research Unit of the Third Xiangya Hospital of Central South University. The principal investigators are Guoping Yang and Chengxian Guo.
Interventions
DRUGDM1001 Transdermal Patch
DM1001 transdermal patch containing pramipexole, administered at cohort-specific doses and application sites.
Matching placebo transdermal patch containing 0 mg per 10 cm2, administered in Cohorts 1 and 3 according to the randomized, double-blind study design.
DRUGPramipexole Extended-Release Tablet
Oral pramipexole extended-release tablets administered at 0.375 mg, 0.75 mg, and 1.5 mg once daily during Weeks 1, 2, and 3, respectively.
Sponsors
The Third Xiangya Hospital of Central South University
Fosun Wanbang (Jiangsu) Pharmaceutical Group Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Criterion 1. Healthy male or female participants aged 18 to 55 years, inclusive, at the time of informed consent. * Criterion 2. Body weight of at least 50 kg for males and at least 45 kg for females. * Criterion 3. BMI between 18 and 28 kg/m², inclusive. * Criterion 4. Able to understand the study procedures and potential risks, provide written informed consent, communicate effectively with the investigator, and comply with all study requirements.
Exclusion criteria
* Criterion 1. Clinically significant disease or dysfunction, including neurological, psychiatric, cardiovascular, gastrointestinal, respiratory, renal, metabolic, endocrine, dermatological, hematological, immunological, or malignant disease. * Criterion 2. Any condition or history of surgery that may affect drug absorption, distribution, metabolism, or excretion, or may place the participant at unacceptable risk. * Criterion 3. Significant history of drug or skin allergy, or known allergy to any study intervention component. * Criterion 4. Current or previous psychiatric or brain disorder, suicide risk according to the Columbia-Suicide Severity Rating Scale, or history of self-harm. * Criterion 5. History of drug or substance abuse, positive urine drug screen, alcohol abuse, or positive alcohol breath test. * Criterion 6. Smoking of 5 or more cigarettes per day or consumption of 5 or more cups of coffee or tea per day within the specified period, or inability to discontinue these activities during the study. * Criterion 7. Unhealed skin disease or unsuitable application sites, including excessive hair, sunburn, raised moles, scars, wounds, tattoos, abnormal pigmentation, excessive sweating, or other conditions that may interfere with patch application or skin assessment. * Criterion 8. Pregnancy or breastfeeding, positive pregnancy test, plans for pregnancy during the study or within 6 months after the study, or unwillingness to use effective contraception. * Criterion 9. Clinically significant abnormalities in physical examination, vital signs, laboratory tests, chest imaging, ultrasound, or electrocardiogram, including QTcF of 450 ms or greater in males or 460 ms or greater in females. * Criterion 10. Resting pulse rate below 55 or above 100 beats per minute, systolic blood pressure below 90 or at least 140 mmHg, or diastolic blood pressure below 60 or at least 90 mmHg. * Criterion 11. Positive test results for HBsAg, HCV antibody, HIV antibody, or syphilis testing. * Criterion 12. ALT or creatinine above the upper limit of normal, or serum prolactin greater than twice the upper limit of normal. * Criterion 13. Blood donation or blood loss meeting the protocol-defined limits, recent surgery, use of any medication within 2 weeks before study dosing, participation in another clinical trial within 3 months, or vaccination within 30 days. * Criterion 14. Any other condition, poor compliance, or circumstance that, in the investigator's judgment, makes the participant unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, or Adverse Events Leading to Study Withdrawal | From first administration through the end of safety follow-up, up to Day 11, Day 24, Day 25, or Day 46 depending on the cohort. | Incidence, severity, seriousness, and relationship to study intervention, including changes in vital signs, physical examination, 12-lead ECG, hematology, urinalysis, clinical chemistry, coagulation, and prolactin. |
| Maximum Observed Plasma Concentration (Cmax) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | Cmax derived from observed plasma pramipexole concentration-time data following administration of the DM1001 transdermal patch. |
| Time to Maximum Observed Plasma Concentration (Tmax) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | Tmax derived from observed plasma pramipexole concentration-time data following administration of the DM1001 transdermal patch. |
| Terminal Elimination Rate Constant (Lambda z) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | Lambda z is the terminal elimination rate constant of pramipexole estimated from the terminal log-linear portion of the plasma concentration-time curve following administration of the DM1001 transdermal patch. |
| Apparent Terminal Elimination Half-Life (t1/2) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | The apparent terminal elimination half-life is the time required for the plasma concentration of pramipexole to decrease by one-half during the terminal elimination phase following administration of the DM1001 transdermal patch. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Pramipexole Following DM1001 Transdermal Patch Administration. | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | AUC0-t is the area under the plasma pramipexole concentration-time curve from time zero to the time of the last quantifiable plasma concentration following administration of the DM1001 transdermal patch. |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | AUC0-inf is the total area under the plasma pramipexole concentration-time curve from time zero extrapolated to infinity following administration of the DM1001 transdermal patch. |
| Apparent Total Clearance (CL/F) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | CL/F is the apparent total clearance of pramipexole from plasma following administration of the DM1001 transdermal patch. |
| Apparent Volume of Distribution (Vd/F) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | Vd/F is the apparent volume of distribution of pramipexole during the terminal elimination phase following administration of the DM1001 transdermal patch. |
| Mean Residence Time (MRT) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | MRT is the estimated average time that pramipexole remains in the body following administration of the DM1001 transdermal patch. |
| Percentage of AUC Extrapolated to Infinity (AUC%Extrap) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | AUC%Extrap is the percentage of AUC0-inf attributable to extrapolation from the last quantifiable plasma concentration to infinity following administration of the DM1001 transdermal patch. |
| Maximum Observed Steady-State Plasma Concentration (Css,max) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | Css,max is the highest observed plasma concentration of pramipexole during a dosing interval at steady state following administration of the DM1001 transdermal patch. |
| Time to Maximum Observed Steady-State Plasma Concentration (Tss,max) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | Tss,max is the elapsed time from administration to the maximum observed plasma concentration of pramipexole during a dosing interval at steady state following administration of the DM1001 transdermal patch. |
| Minimum Observed Steady-State Plasma Concentration (Css,min) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | Css,min is the lowest observed plasma concentration of pramipexole during a dosing interval at steady state following administration of the DM1001 transdermal patch. |
| Area Under the Plasma Concentration-Time Curve Over a Dosing Interval at Steady State (AUCss) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | AUCss is the area under the plasma pramipexole concentration-time curve over one dosing interval at steady state following administration of the DM1001 transdermal patch. |
| Accumulation Ratio Based on AUC (RAUC) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | RAUC is the accumulation ratio of pramipexole calculated by comparing the area under the plasma concentration-time curve at steady state with the corresponding area under the curve after the initial administration of the DM1001 transdermal patch. |
| Accumulation Ratio Based on Cmax (RCmax) of Pramipexole Following DM1001 Transdermal Patch Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | RCmax is the accumulation ratio of pramipexole calculated by comparing the maximum observed plasma concentration at steady state with the maximum observed plasma concentration after the initial administration of the DM1001 transdermal patch. |
| Maximum Observed Plasma Concentration (Cmax) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From pre-dose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | Cmax derived from observed plasma pramipexole concentration-time data following administration of oral pramipexole extended-release tablets. |
| Time to Maximum Observed Plasma Concentration (Tmax) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | Tmax derived from observed plasma pramipexole concentration-time data following administration of oral pramipexole extended-release tablets. |
| Terminal Elimination Rate Constant (Lambda z) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | Lambda z is the terminal elimination rate constant of pramipexole estimated from the terminal log-linear portion of the plasma concentration-time curve following administration of oral pramipexole extended-release tablets. |
| Apparent Terminal Elimination Half-Life (t1/2) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | The apparent terminal elimination half-life is the time required for the plasma concentration of pramipexole to decrease by one-half during the terminal elimination phase following administration of oral pramipexole extended-release tablets. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration. | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | AUC0-t is the area under the plasma pramipexole concentration-time curve from time zero to the time of the last quantifiable plasma concentration following administration of oral pramipexole extended-release tablets. |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | AUC0-inf is the total area under the plasma pramipexole concentration-time curve from time zero extrapolated to infinity following administration of oral pramipexole extended-release tablets. |
| Apparent Total Clearance (CL/F) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | CL/F is the apparent total clearance of pramipexole from plasma following administration of oral pramipexole extended-release tablets. |
| Apparent Volume of Distribution (Vd/F) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | Vd/F is the apparent volume of distribution of pramipexole during the terminal elimination phase following administration of oral pramipexole extended-release tablets. |
| Mean Residence Time (MRT) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | MRT is the estimated average time that pramipexole remains in the body following administration of oral pramipexole extended-release tablets. |
| Percentage of AUC Extrapolated to Infinity (AUC%Extrap) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through the last pharmacokinetic sample: Day 11 for Cohorts 1, 5, and 6; Day 24 for Cohort 2; Day 25 for Cohort 3; and Day 46 for Cohort 4. | AUC%Extrap is the percentage of AUC0-inf attributable to extrapolation from the last quantifiable plasma concentration to infinity following administration of oral pramipexole extended-release tablets. |
| Maximum Observed Steady-State Plasma Concentration (Css,max) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | Css,max is the highest observed plasma concentration of pramipexole during a dosing interval at steady state following administration of oral pramipexole extended-release tablets. |
| Time to Maximum Observed Steady-State Plasma Concentration (Tss,max) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | Tss,max is the elapsed time from administration to the maximum observed plasma concentration of pramipexole during a dosing interval at steady state following administration of oral pramipexole extended-release tablets. |
| Minimum Observed Steady-State Plasma Concentration (Css,min) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | Css,min is the lowest observed plasma concentration of pramipexole during a dosing interval at steady state following administration of oral pramipexole extended-release tablets. |
| Area Under the Plasma Concentration-Time Curve Over a Dosing Interval at Steady State (AUCss) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | AUCss is the area under the plasma pramipexole concentration-time curve over one dosing interval at steady state following administration of oral pramipexole extended-release tablets. |
| Accumulation Ratio Based on AUC (RAUC) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | RAUC is the accumulation ratio of pramipexole calculated by comparing the area under the plasma concentration-time curve at steady state with the corresponding area under the curve after the initial administration of oral pramipexole extended-release tablets. |
| Accumulation Ratio Based on Cmax (RCmax) of Pramipexole Following Oral Pramipexole Extended-Release Tablet Administration | From predose through completion of steady-state pharmacokinetic sampling: Day 24 for Cohort 2 and Day 46 for Cohort 4. | RCmax is the accumulation ratio of pramipexole calculated by comparing the maximum observed plasma concentration at steady state with the maximum observed plasma concentration after the initial administration of oral pramipexole extended-release tablets. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Skin Irritation at the Application Site Assessed Using the Predefined Skin Reaction Score | Before patch application and at 1, 24, and 48 hours after patch removal; assessment may be extended to Day 7 or Day 14 if necessary. | Number of participants with skin irritation at the patch application and control sites, assessed using the predefined skin reaction score (range 0-7) and other effect categories (A-H). The number and percentage of participants in each score category will be reported. |
| Mean DM1001 Patch Adhesion Score at Each Scheduled Assessment | Within 1 hour after each patch application and at 12, 24, and every 24 hours thereafter through patch removal at 168 hours. | Patch adhesion assessed at 0, 12, and 24 hours after application and every 24 hours thereafter until patch removal. |
| Mean Transdermal Absorption Percentage of Pramipexole From DM1001 Patches Based on Residual Drug Content | Assessed at each scheduled patch removal (168 hours after application): Day 8 for Cohorts 1, 5, and 6; Days 8, 15, and 22 for Cohort 3; and Days 8, 15, 22, 29, 36, and 43 for Cohort 4. | Used DM1001 patches will be collected at each scheduled patch removal. The transdermal absorption percentage of pramipexole from each patch will be derived from the residual drug content measured in the used patch using the prespecified calculation method. |
Outcome results
None listed