A Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Multiple-Dose Phase I Clinical Study to Evaluate the Safety, Tolerance, and Pharmacokinetic Profiles of Timolol Maleate Gel in Healthy Chinese Adult Subjects
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Auson Pharmaceuticals Inc.
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Local tolerance
Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy adult male or female subjects aged 18-55 years (including the cut point, subject to the time of signing the ICF);
- •Subjects with the body mass index (BMI) of 19-26 kg/m2 (including the cut point), where the body weight should be ≥ 50 kg for male subjects and ≥ 45 kg for female subjects;
- •Subjects who have no pregnancy plan, voluntarily adopt effective birth controls, and have no sperm donation or egg donation plan during the study until 3 months after the last dose. For specific birth controls, see Appendix 1: Birth Control, Definition of Female Subjects of Childbearing Age, and Contraception Requirements;
- •Subjects fully understand the study objective, nature, methods and possible adverse reactions, voluntarily become subjects, and sign the ICFs;
- •Subjects who have no skin damage or scar or skin disease at the administration site; Subjects who can complete the trial as required in the protocol.
Exclusion Criteria
- •Subjects who are allergic to timolol maleate and similar drugs;
- •Subjects who have any difficulty in venous blood collection;
- •Subjects who have cardiogenic shock, Grade I or Grade III atrioventricular block, cardiac failure, sinus bradycardia, hypotension, and CS as assessed by the study physician;
- •Subjects who have bronchial asthma, airway sensitive disease, ventilation difficult or other pulmonary disorders;
- •Subjects who have had a history of drug abuse in the past five years or used drugs within the 3 months before the study; or subjects who are positive in the drug abuse screening test in the screening phase;
- •Subjects who have smoked more than 5 cigarettes a day within the 3 months before screening;
- •Subjects who have consumed more than 14 units of alcohol (1 unit of alcohol = 360 mL beer or 45 mL 40% spirits or 150 mL wine) weekly within 6 months before the screening or have taken alcohol-containing products 48 h pre-dose, or were or positive in the alcohol breath test in the screening phase and/or the baseline phase;
- •Subjects who have used any drug that induces or inhibits liver metabolic enzymes within 28 days pre-dose in the study;
- •Subjects who have used any Rx, OTC or Chinese herbal medicine within 14 days pre-dose in the study;
- •Subjects who have took food or drink (such as grapefruit) containing enzymes that can induce or inhibit liver metabolism within 7 days pre-dose in the study;
Arms & Interventions
Group 2-0.5%TM
Participants will be randomized to receive 0.5%TM or matching placebo 2 times a day.
Intervention: Timolol Maleate Gel (Drug)
Group 2-0.5%TM
Participants will be randomized to receive 0.5%TM or matching placebo 2 times a day.
Intervention: Placebo (Drug)
Group 3-0.5%TM
Participants will be randomized to receive 0.5%TM or matching placebo 3 times a day.
Intervention: Timolol Maleate Gel (Drug)
Group 3-0.5%TM
Participants will be randomized to receive 0.5%TM or matching placebo 3 times a day.
Intervention: Placebo (Drug)
Group 1-0.5%TM
Participants will be randomized to receive 0.5%TM or matching placebo 1 time a day.
Intervention: Timolol Maleate Gel (Drug)
Group 1-0.5%TM
Participants will be randomized to receive 0.5%TM or matching placebo 1 time a day.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Local tolerance
Time Frame: 13 Days
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".
Adverse events
Time Frame: Throughout study completion, an average 13 days
Frequency, severity and relatedness of adverse events
Vital signs (blood pressure)
Time Frame: the screening phase, Day -1, Day 1, 3, 6, 9, 12, and Day 13.
Number of participants with clinically significant changes in vital signs (blood pressure)
Vital signs (temperature)
Time Frame: the screening phase, Day -1, Day 1, 3, 6, 9, 12, and Day 13.
Number of participants with clinically significant changes in vital signs (temperature)
Vital signs (pulse rate)
Time Frame: the screening phase, Day -1, Day 1, 3, 6, 9, 12, and Day 13.
Number of participants with clinically significant changes in vital signs (pulse rate)
Laboratory tests
Time Frame: the screening phase, the baseline phase, and on Days 6 and 13.
Number of participants with clinical laboratory abnormalities (including hematology, blood biochemistry and urinalysis).
Physical examinations
Time Frame: the screening phase, baseline phase and on Day 13
Number of participants with clinically significant changes in physical examinations.
12-lead ECG
Time Frame: the screening phase, baseline phase, Day 1, 3, 6, 9, 12, and Day 13.
Number of participants with clinically significant changes in 12-lead ECG.
Secondary Outcomes
- Tmax(Day1 to Day13)
- Cmax(Day1 to Day13)
- AUC0-t(Day1 to Day13)
- AUC0-inf(Day1 to Day13)
- λz(Day1 to Day13)
- t1/2(Day1 to Day13)
- %AUCex(Day1 to Day13)