The purpose of this study is to characterize the pharmacokinetics (PK), safety and tolerability of topically applied umeclidinium following single dose topical administration. The results from this study will be used to 1) improve our understanding of the risk of systemic accumulation upon chronic administration, 2) support dosing recommendations in a 2a/2b study for axillary administration and, potentially, a separate combined 2a/2b study for palmar administration, and 3) confirm whether the same formulation can be used for axillary and palmar application for the next studies.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Umeclidinium will be supplied as clear, colorless solution, free from visible particulates, single dose, topical solution in clear glass jars. Dosage of 18.5 mg of Umeclidinium per gram is equivalent to 22 mg per gram of the bromide salt.
GSK Investigational Site
Zuidlaren, Netherlands
PK Assessment (Cmax) for [14C] umeclidinium and total radioactivity
Blood sample will be collected for PK assessment including maximum observed plasma concentration (Cmax).
Time frame: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
PK Assessment (tmax) for [14C] umeclidinium and total radioactivity
Blood sample will be collected for PK assessment including time to Cmax (tmax).
Time frame: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
PK Assessment (AUC) for [14C] umeclidinium and total radioactivity
Blood sample will be collected for PK assessment including area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable sample (AUC0-last), AUC from time zero to 12 hrs or 24 hrs (AUC0-12 and AUC0-24, respectively), AUC from time zero to time infinity \[AUC (0-infinity)\].
Time frame: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
PK Assessment (t1/2) for [14C] umeclidinium and total radioactivity
Blood sample will be collected for PK assessment including apparent terminal phase half-life (t1/2).
Time frame: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
Compartmental modeling of absorption rate for [14C] umeclidinium
Compartmental modeling may be conducted to characterize the absorption rate constants.
Time frame: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
Compartmental modeling of elimination rate for [14C] umeclidinium
Compartmental modeling may be conducted to characterize the elimination rate constants.
Time frame: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
Determine the amount of Umeclidinium absorbed in the skin
Evaluations will be determined by subtracting the amount of drug recovered from skin and tape strips
Time frame: Day 1 (and Day 2 if required)
Safety Assessment for AEs
Safety evaluations will be based on the incidence, intensity and type of adverse events (AEs)
Time frame: From first dose up to Follow-up (Day 14)
Safety Assessment for ECGs, and telemetry
Safety evaluations will be based on the 12-lead electrocardiograms (ECGs) and Lead II ECG monitoring.
Time frame: From Screening up to Follow-up (Day 14)
Safety Assessment for hematology laboratory parameters
Safety evaluations will be based on hematology laboratory results
Time frame: From Screening up to Follow-up (Day 14)
Safety Assessment for measurement of blood pressure
Safety evaluations will be based on the clinically significant changes in vital signs includes systolic and diastolic blood pressure
Time frame: From Screening up to Follow-up (Day 14)
Number of subjects with application site skin irritation
Safety evaluations will be based on application site skin irritation. The number of subjects with application site skin irritation (as measured by the Skin Tolerability Assessment Scale) will be summarized.
Time frame: From Day 1 up to Follow-up (Day 14)
Safety Assessment for clinical chemistry laboratory parameters
Safety evaluations will be based on the clinical chemistry laboratory results
Time frame: From Screening up to Follow-up (Day 14)
Safety Assessment for measurement of pulse rate
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Safety evaluations will be based on the clinically significant changes in vital signs includes pulse rate
Time frame: From Screening up to Follow-up (Day 14)