This study is intended to produce information on the pharmacokinetic characteristics (uptake into and elimination from the body) of two new patch formulations of the analgesic buprenorphine as compared to the reference patch Transtec (Registered Trademark) 35 micrograms per hour (μg/h) in order to assess the suitability of the test formulations for a later confirmatory bioequivalence study. In addition to a reduced buprenorphine load, the new patch formulations may potentially provide improved wearing properties. A placebo patch formulation of the respective test or reference patch will be applied simultaneously to explore the skin tolerability and skin adhesiveness of the patch formulations. Furthermore, the safety and tolerability of the treatments will be assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Buprenorphine transdermal patch formulation, containing 9 milligrams buprenorphine in an active surface area of 25 square centimeters.
Buprenorphine transdermal patch formulation, containing 3.8 milligrams buprenorphine in an active surface area of 10 square centimeters.
Transtec (Registered Trademark) transdermal patch containing 20 milligrams buprenorphine in an active surface area of 25 square centimeters, release rate 35 micrograms per hour.
Placebo patch to T1.
Placebo patch to T2.
Placebo patch to R.
Swiss Pharma Contract
Allschwil, Switzerland
Area under the concentration-time extrapolated to infinity (AUC)
For the analysis of buprenorphine in human plasma a liquid chromatography-double quadrupole mass spectrometry (LC-MS/MS)-validated method will be used. AUC is calculated by summation of the partial areas AUC(0-t) and the residual area AUC(t-∞) represents the recalculated plasma concentration at the last sampling time point with a quantifiable concentration. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
Area under the concentration-time curve up the last quantifiable plasma concentration (AUC0-t)
Area under data from administration until the last sampling point (tz) with a quantifiable concentration, calculated by the linear/log trapezoidal method, i.e., the linear trapezoidal rule is applied up to Cmax and then the log trapezoidal rule is applied for the remainder of the curve. If multiple maxima are observed in the concentration-time curve, Cmax is assigned to the first maximum. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
Maximum plasma concentration (Cmax) of buprenorphine
Maximum plasma concentration, highest observed plasma concentration of the measured concentration-time profile. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
Time to attain maximum plasma concentration (tmax)
Time of maximum concentration, time after administration at which Cmax occurs. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration (tlag)
Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
Terminal half-life (t1/2,z)
Apparent terminal elimination half-life. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
Assessment of skin adhesiveness
Reading of skin adhesiveness of the patch will be performed for test/reference and placebo administration sites each on Days 1-5 (every 12 hours following patch application and at 96 hours following patch application immediately before patch removal).
Time frame: Day 1 to Day 5
Assessment of skin irritation
Assessment of skin irritation will be performed (for test/reference and placebo patch each) at baseline, on Days 1-5 (immediately and 20 min following patch removal), and on Days 8-10 (120 hours following patch application).
Time frame: At baseline, on Days 1-5 (immediately and 20 min following patch removal), on Days 8-10 (120 hours following patch application)
Incidence of treatment emergent adverse events
Number of adverse events and participants with adverse events.
Time frame: From Day 1 (patch application) until Day 12 (Final examination)
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