A Study of Atropine Sulfate in Healthy Chinese Volunteers

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

To evaluate the systemic pharmacokinetics and the safety of atropine sulfate eye drops in healthy volunteers.

Study Overview

• Status: Recruiting
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: Atropine sulfate eye drops

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)

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Christopher LEUNG; Phone Number: +852 25181430; Email: cleung21@hku.hk

Study Locations

• China
  • Hong Kong, China
    • Recruiting
    • HKU Eye Centre
    • Contact: Christopher LEUNG; Phone Number: +852 25181430; Email: cleung21@hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 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;
2. 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;
3. 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:

1. Subject with any eye with corrected visual acuity <1.0, clinically significant abnormal intraocular pressure, slit lamp and fundus examination.
2. Subject with history of eye diseases, including the history of internal eye surgery or laser surgery.
3. 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.
4. Subject with clinically significant history of allergies, such as drug allergies, especially those who are allergic to any component of atropine sulfate eye drops.
5. On average, subject smokes more than 5 cigarettes per day or that who ex-smokes less than 3 months.
6. 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.
7. Subject has used any local or systemic drugs (including any prescription or over-the-counter drugs) within 2 weeks before screening.
8. Subject has participated in interventional clinical trials within 3 months before screening.
9. Subject who has worn contact lenses or cosmetic contact lenses within 1 weeks before screening.
10. Subject who is pregnant or breastfeeding.
11. The investigator believes that the subject is not suitable to participate in the trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Zhaoke (Hong Kong) Ophthalmology Pharmaceutical Limited
• Investigators: Principal Investigator: Christopher LEUNG, HKU Eye Centre

Study record dates

Study Major Dates

• Study Start (Anticipated): May 9, 2023
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: April 23, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Estimate): May 11, 2023

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Pharmaceutical Solutions; Mydriatics; Ophthalmic Solutions; Atropine
• Other Study ID Numbers: ZKO(HK)-ATP-202111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No