Safety, Tolerability, and Pharmacokinetics of DM1001 Transdermal Patch in Healthy Chinese Participants

Participants receive DM1001 transdermal patch in Cohorts 1, 3, 4, 5, and 6. Doses include 2.8 mg, 5.6 mg, and 11.2 mg according to the cohort-specific schedule. The patch is applied to the upper arm, upper back, or outer thigh according to the cohort. Cohorts 1 and 3 are randomized in a 3:1 ratio to DM1001 or matching placebo, whereas Cohorts 4, 5, and 6 are open-label.

DM1001 transdermal patch containing pramipexole, administered at cohort-specific doses and application sites.

Participants in Cohorts 1 and 3 receive matching placebo transdermal patch according to the randomized, double-blind, placebo-controlled design. Participants are randomized in a 3:1 ratio to DM1001 or matching placebo.

Matching placebo transdermal patch containing 0 mg per 10 cm2, administered in Cohorts 1 and 3 according to the randomized, double-blind study design.

Participants in Cohort 2 receive oral pramipexole extended-release tablets at 0.375 mg once daily during Week 1, 0.75 mg once daily during Week 2, and 1.5 mg once daily during Week 3.

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.

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.

Cmax derived from observed plasma pramipexole concentration-time data following administration of the DM1001 transdermal patch.

Tmax derived from observed plasma pramipexole concentration-time data following administration of the DM1001 transdermal patch.

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.

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.

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.

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.

CL/F is the apparent total clearance of pramipexole from plasma following administration of the DM1001 transdermal patch.

Vd/F is the apparent volume of distribution of pramipexole during the terminal elimination phase following administration of the DM1001 transdermal patch.

MRT is the estimated average time that pramipexole remains in the body following administration of the DM1001 transdermal patch.

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.

Css,max is the highest observed plasma concentration of pramipexole during a dosing interval at steady state following administration of the DM1001 transdermal patch.

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.

Css,min is the lowest observed plasma concentration of pramipexole during a dosing interval at steady state following administration of the DM1001 transdermal patch.

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.

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.

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.

Cmax derived from observed plasma pramipexole concentration-time data following administration of oral pramipexole extended-release tablets.

Tmax derived from observed plasma pramipexole concentration-time data following administration of oral pramipexole extended-release tablets.

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.

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.

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.

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.

CL/F is the apparent total clearance of pramipexole from plasma following administration of oral pramipexole extended-release tablets.

Vd/F is the apparent volume of distribution of pramipexole during the terminal elimination phase following administration of oral pramipexole extended-release tablets.

MRT is the estimated average time that pramipexole remains in the body following administration of oral pramipexole extended-release tablets.

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.

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.

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.

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.

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.

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.

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.

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.

Patch adhesion assessed at 0, 12, and 24 hours after application and every 24 hours thereafter until patch removal.

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.