The goal of this clinical study is to obtain the bioavailability of the test patch of a generic formulation of Selegiline TDS 6mg/24 hours by Corium Innovations against the comparator (EMSAM), and the systemic and local safety and tolerability will be also observed and evaluated.
This is a pilot, single-dose, single-centre, open-label, randomised, 2-way crossover study (2 treatments, 2 periods and 2 sequences) of a generic test formulation of Selegiline TDS 6 mg/24 hours with the comparator EMSAM® TDS 6 mg/24 hours, with at least 14 days washout period, recruiting around 12 healthy male and female subjects. For each study period, subjects will be admitted and confined in the clinical study site the night before the study day from at least 10 hours before dosing and they will be discharged once all PK, safety and tolerability are completed at 36 hours after dosing. Subjects will be required to return for subsequent PK, safety and tolerability at 48-, 72- and 96-hours post-dosing. The clinic will follow up by telephone 7 ± 3 days after completion of the study. Pharmacokinetic Blood Sampling: PK blood samples will be collected before dosing and at 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 24, 30, 36, 48, 72, 96 hours after dosing. Pharmacokinetics: PK parameters include AUC0-t, AUC0-∞, Cmax, tmax, t½, tlag (if applicable), λz, and Mean residence time (MRT) will be evaluated for Selegiline. Safety: Safety will be assessed on all subjects who participate in the study from the beginning to the end. Adverse events (AEs), abnormal vital signs, abnormal ECG results, abnormal physical examination findings and abnormal clinical laboratory test results will be reviewed on a subject-to-subject basis.
Study Type
OBSERVATIONAL
Enrollment
12
Selegiline concentrations will be measured in blood plasma using a validated liquid chromatography tandem mass spectrometry method from Selegiline TDS (test formulation 6mg/24 hours) and EMSAM (6mg/24 hours). The analytical laboratory will be blinded as to samples which are the test and reference products.
Sarawak General Hospital
Samoran, Sarawak, Malaysia
Hospital Ampang
Ampang, Selangor, Malaysia
Plasma Pharmacokinetic-AUC 0-t
The area under the plasma concentration-time curve from time 0 to the last measurable concentration is calculated by the linear/log trapezoidal method where the liner trapezoidal method is applied up to Tmax and the log trapezoidal method is used after Tmax.
Time frame: 22 days
Plasma Pharmacokinetic-AUC 0-∞
The area under the plasma concentration-time curve from time 0 to infinity is calculated as the sum of AUC0-t and Ct/Kel, where Ct is the last measurable concentration.
Time frame: 22 days
Plasma Pharmacokinetic-Cmax
The maximum plasma concentration following drug administration
Time frame: 22 days
Plasma Pharmacokinetic-Tmax
The time to achieve maximum plasma concentration is determined directly from the individual plasma concentration-time curves
Time frame: 22 days
Plasma Pharmacokinetic-T1/2
The terminal elimination half-life is calculated as 0.693/Kel
Time frame: 22 days
Plasma Pharmacokinetic-Tlag
The time prior to achieving the first measurable plasma concentration (if applicable)
Time frame: 22 days
Plasma Pharmacokinetic-MTR
The mean residence time
Time frame: 22 days
Plasma Pharmacokinetic-λz (Lambda z)
Individual estimate of the terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves
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Time frame: 22 days
Safety-Topic Skin Irritation
Each application site will receive a separate dermal response score and other effect score. Dermal response scores require that at least 25% or more of the patch area demonstrate an observable response. The percentage of the patch area demonstrating an observable response will also be recorded. "Strong" reaction to the transdermal patch is defined as a dermal response score of 3-7 or any dermal response score combined with other effect score of 4 or greater.
Time frame: 22 days