A Study of Atropine Sulfate in Healthy Chinese Volunteers

Study Overview
=================
Brief Summary
-----------------
To evaluate the systemic pharmacokinetics and the safety of atropine sulfate eye drops in healthy volunteers.

Detailed Description
-----------------
This is a randomized, open-label, phase I clinical study evaluating the systemic pharmacokinetics and safety of atropine sulfate eye drops in healthy Chinese volunteers.Three concentrations will be investigated, each concentration group must contain both male and female subjects, and each subject receives only one concentration of atropine sulfate eye drop in this study. The three treatment arms are: Atropine sulfate dose A (low concentration) Atropine sulfate dose B (medium concentration) Atropine sulfate dose C (high concentration)

Official Title
-----------------
A Randomized, Open-label Phase I Clinical Study to Evaluate the Systemic Pharmacokinetics and Safety of Atropine Sulfate Eye Drops in Healthy Chinese Volunteers

Conditions
-----------------
Pharmacokinetics

Intervention / Treatment
-----------------
* Drug: Atropine sulfate eye drops


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy subject is a male or female Chinese with his/her biological parents and grandparents are of Chinese ethnicity, aged 18-45 (including cut-off value) at screening; Subject with a body mass index (BMI) between 19.0-26.0kg/m2 (including cut-off value), male weight ≥50.0kg, female weight ≥45.0kg at screening and D0; Subject is in good health, as determined by the investigator, based on medical history, no findings of clinical significant abnormalities at physical examination, vital signs, electrocardiogram and clinical laboratory tests at screening and D0; Exclusion Criteria: Subject with any eye with corrected visual acuity <1.0, clinically significant abnormal intraocular pressure, slit lamp and fundus examination. Subject with history of eye diseases, including the history of internal eye surgery or laser surgery. Subject with clinically significant history of the central nervous system, mental, cardiovascular, kidney, liver, respiratory, metabolic, and musculoskeletal system diseases etc., which may endanger the safety of the subject or affect the results of the study, as judged by the investigator. Subject with clinically significant history of allergies, such as drug allergies, especially those who are allergic to any component of atropine sulfate eye drops. On average, subject smokes more than 5 cigarettes per day or that who ex-smokes less than 3 months. Subject has used any topical or systemic antimuscarinic/anticholinergic drugs (e.g., atropine, 1-hyoscyamine, tropicamide, chlorpheniramine, diphenhydramine, oxytropine, cyclic antidepressants, etc.) within 3 weeks before screening. Subject has used any local or systemic drugs (including any prescription or over-the-counter drugs) within 2 weeks before screening. Subject has participated in interventional clinical trials within 3 months before screening. Subject who has worn contact lenses or cosmetic contact lenses within 1 weeks before screening. Subject who is pregnant or breastfeeding. The investigator believes that the subject is not suitable to participate in the trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atropine sulfate Concentration A<br>Subjects will be treated with atropine sulfate eye drop (at dosage Concentration A), administered once daily (QD). | Drug: Atropine sulfate eye drops<br>* One drop once daily<br>* Other names: Atropine sulfate;|
| Experimental: Atropine sulfate Concentration B<br>Subjects will be treated with atropine sulfate eye drop (at dosage Concentration B), administered once daily (QD). | Drug: Atropine sulfate eye drops<br>* One drop once daily<br>* Other names: Atropine sulfate;|
| Experimental: Atropine sulfate Concentration C<br>Subjects will be treated with atropine sulfate eye drop (at dosage Concentration C), administered once daily (QD). | Drug: Atropine sulfate eye drops<br>* One drop once daily<br>* Other names: Atropine sulfate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Time of Cmax (Tmax) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Time of half-life (t1/2) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Area Under time-concentration Curve from 0 to last draw time (AUC0-t) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Area Under time-concentration Curve from 0 to infinity time (AUC(0-∞)) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Minimum concentration (Cmin) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Volume of distribution (Vd) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Elimination rate constant (Kel) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Clearance (CL) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 
| Apparent Clearance (CL/F) | Measure the concentration of analyte in the blood to evaluate drug pharmacokinetics | From 1 hour before administration to 24 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slit-lamp eye examination results change from baseline to Day 7 | Evaluate the anterior segment of the eye, including the eyelids, cornea, conjunctiva, anterior chamber, iris and lens, and record abnormalities | on Day 0 and Day 7 | 
| Fundoscopy eye examination results change from baseline to Day 7 | Evaluate the condition of the fundus, including the vitreous body, optic disc, macula, peripheral retina and retinal blood vessels | on Day 0 and Day 7 | 
| Intraocular pressure change from baseline to Day 7 | Use non-contact tonometer to measure intraocular pressure | on Day 0 and Day 7 | 
| Vision acuity change from baseline to Day 7 | Using Best-corrected LogMAR scale | on Day 0 and Day 7 | 
| The mean change of pupil diameter from baseline to Day 7 | Use ophthalmic biometry equipment to measure pupil diameter | on Day 0 and Day 7 | 
| The mean change of accommodation amplitude from baseline to Day 7 | Use a Phoropter to measure the accommodation amplitude using the negative lens method | on Day 0 and Day 7 |