The goal of this clinical trial is to to evaluate the safety, tolerance, and pharmacokinetic profiles of Timolol Maleate Gel in healthy Chinese adult subjects. The main questions aim to answer are: • The pharmacokinetic endpoints: Single dose:Tmax, Cmax, etc. Multiple doses:AUC0-t, AUC0-inf, λz, t1/2, etc. • The safety and tolerance endpoints: Physical examination, vital signs, 12-lead ECG, laboratory tests (hematology, blood biochemistry and urinalysis), adverse events, local tolerance. Researchers will compare TM gel to a placebo (a look-alike substance that contains no drug) to see if TM gel works to treat IH.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
28
A 2-day washout phase follows 1 dose on Day 1, the subjects are applied with 0.5% timolol maleate gel one time a day during Day 3-Day 12.
A 2-day washout phase follows 1 dose on Day 1, the subjects are applied with placebo one time a day during Day 3-Day 12.
A 2-day washout phase follows 1 dose on Day 1, the subjects are applied with 0.5% timolol maleate gel 2 times a day during Day 3-Day 12.
A 2-day washout phase follows 1 dose on Day 1, the subjects are applied with placebo 2 times a day during Day 3-Day 12.
A 2-day washout phase follows 1 dose on Day 1, the subjects are applied with 0.5% timolol maleate gel 3 times a day during Day 3-Day 12.
A 2-day washout phase follows 1 dose on Day 1, the subjects are applied with placebo 3 times a day during Day 3-Day 12.
Shanghai Xuhui District Central Hospital
Shanghai, Shanghai Municipality, China
Local tolerance
Local tolerance will be evaluated by an investigator or designated evaluator (e.g., dermatologist) using the blinding method.The intensity (e.g., No evidence of irritation;Minimal erythema that is barely perceptible;Definite erythema that is readily visible and minimal edema or minimal papular response;Erythema and papules, et al) of the skin response is assessed on a 8 point scale.Other response score is assessed from "A" to "H".
Time frame: 13 Days
Adverse events
Frequency, severity and relatedness of adverse events
Time frame: Throughout study completion, an average 13 days
Vital signs (blood pressure)
Number of participants with clinically significant changes in vital signs (blood pressure)
Time frame: the screening phase, Day -1, Day 1, 3, 6, 9, 12, and Day 13.
Vital signs (temperature)
Number of participants with clinically significant changes in vital signs (temperature)
Time frame: the screening phase, Day -1, Day 1, 3, 6, 9, 12, and Day 13.
Vital signs (pulse rate)
Number of participants with clinically significant changes in vital signs (pulse rate)
Time frame: the screening phase, Day -1, Day 1, 3, 6, 9, 12, and Day 13.
Laboratory tests
Number of participants with clinical laboratory abnormalities (including hematology, blood biochemistry and urinalysis).
Time frame: the screening phase, the baseline phase, and on Days 6 and 13.
Physical examinations
Number of participants with clinically significant changes in physical examinations.
Time frame: the screening phase, baseline phase and on Day 13
12-lead ECG
Number of participants with clinically significant changes in 12-lead ECG.
Time frame: the screening phase, baseline phase, Day 1, 3, 6, 9, 12, and Day 13.
Tmax
The pharmacokinetics of single and multiple dose levels in participants will include peak time.
Time frame: Day1 to Day13
Cmax
The pharmacokinetics of single and multiple dose levels in participants will include peak concentration.
Time frame: Day1 to Day13
AUC0-t
The pharmacokinetics of single and multiple dose levels in participants will include area under drug concentration-time curve.
Time frame: Day1 to Day13
AUC0-inf
area under drug concentration-time curve (AUC0-t) from 0 to t for the last accurately measurable concentration, area under drug concentration-time curve from 0 to infinity
Time frame: Day1 to Day13
λz
The pharmacokinetics of single and multiple dose levels in participants will include elimination rate constant.
Time frame: Day1 to Day13
t1/2
The pharmacokinetics of single and multiple dose levels in participants will include elimination half-life.
Time frame: Day1 to Day13
%AUCex
The pharmacokinetics of single and multiple dose levels in participants will include AUC extrapolation percentage.
Time frame: Day1 to Day13
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