A Clinical Trial to Evaluate Tolerability and Pharmacokinetics of HL217 Eye Drop in Healthy Male Subjects

Healthy Subject Clinical Trial

Official title:

A Dose Block-randomized, Double-blind, Placebo Controlled, Dose-escalation Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics After Single Dosing of HL217 Eye Drop in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03650608
• Other study ID #: HL217-101
• Status: Completed
• Phase: Phase 1
• Start date: August 2016
• Est. completion date: August 2017

Study information

• Verified date: August 2018
• Source: Hanlim Pharm. Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability and PK parameters in healthy subjects.

Description:

The purpose of this study is to evaluate the safety, tolerability and PK parameters of HL217 after single eye drop administration at different doses in healthy subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Healthy male subject, aged between 18 and 50 years inclusive

2. Non-smoker subject or smoker of not more than 10 cigarettes a day and able to stop smoking 24 hour prior to admission until discharge

3. Body weight = 50 kg and BMI between 18 and 30 kg/m²

4. Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination) including complete ocular examination

5. Normal Blood Pressure (BP) and Heart Rate (HR) after 10 minutes in supine position:

• 90 mmHg = Systolic Blood Pressure (SBP) = 140 mmHg

• 45 mmHg = Diastolic Blood Pressure (DBP) = 90 mmHg

• 40 bpm = HR = 100 bpm

• Or considered NCS by investigators

6. Normal ECG recording on a 12-lead ECG:

• 120 < PR < 200 ms

• QRS < 120 ms

• QTcf = 430 ms

• No sign of any trouble of sinusal automatism

• Or considered NCS by investigators

7. Laboratory parameters within the normal range of the laboratory (haematological, blood chemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator

8. Normal dietary habits

9. Signing a written informed consent prior to selection

Exclusion Criteria:

1. Any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic, infectious or ocular disease

2. Frequent headaches and / or migraine, recurrent nausea and / or vomiting

3. Symptomatic hypotension whatever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in SBP or DBP equal to or greater than 20 mmHg within two minutes when changing from the supine to the standing position

4. Blood donation (including in the frame of a clinical trial) within 2 months before administration or apheresis within 20 days before administration

5. General anaesthesia within 3 months before administration

6. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician (including allergy to fluorescein)

7. Inability to abstain from intensive muscular effort

8. No next of kin, easily accessible, in case of emergency

9. Any drug or herbal medicine intake (except paracetamol) during the last 14 days prior to the first administration, any over the counter medicine or vitamin during the last 7 days prior to the first administration

10. Subjects who have taken drug metabolizing enzyme inducing agents and inhibitors such as barbitals within a month prior to the first administration

11. History or presence of drug or alcohol abuse (alcohol consumption > >21 units per week)

12. Excessive consumption of beverages with xanthine bases (> 5 cups or glasses / day) and not able to stop 24h prior to admission until discharge

13. Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2

14. Major surgery (general or ocular) within 28 days prior to randomization or major surgery planned during the next 6 months

15. Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development

16. Subjects within an exclusion period of a previous study or subjects who have taken any investigational product from other clinical trials within 60 days from the start of the study (from the administration of investigational product)

17. Subjects with previous participation in the current study

18. Subject under administrative or legal supervision

19. Subjects with an allergy to Fluorescein

20. History of any ocular surgery within the past 6 months prior to study participation

21. Subject who have intraocular pressure > 21 mmHg

22. Subject with acute or chronic eye problems that require eye drop at the time of screening

23. Best-corrected ETDRS visual acuity score = 85 (Snellen equivalent 20/20)

24. Subject who need to wear contact lens during the study.

Related Conditions & MeSH terms

• Healthy Subject

Intervention

Drug:
• Cohort 1: HL217 Ophathalmic Solution QD
Cohort 1 (Once a day)
• Cohort 2: HL217 Ophathalmic Solution BID
Cohort 2 (Twice a day)
• Cohort 3: HL217 Ophthalmic Solution QID
Cohort 3 (Four times a day)
• Placebo Ophthalmic solution
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hanlim Pharm. Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical parameter: Adverse Events (AE)	AEs will be coded according to the MedDRA. They will be classified into pre-defined standard categories according to chronological criteria	During 72hours
Primary	Local tolerance: Redness, Tingling and Other ophthalmic adverse events	Redness, tingling and others should be checked	During 72hours
Secondary	Pharmacokinetic assessment: Cmax	observed maximum plasma concentration of HL217	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour
Secondary	Pharmacokinetic assessment: Tmax	first time to reach Cmax	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour
Secondary	Pharmacokinetic assessment: AUClast	area under the plasma concentration curve from administration up to the last quantifiable concentration at time 72h	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour
Secondary	Pharmacokinetic assessment: AUCinf	area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour
Secondary	Pharmacokinetic assessment: Kel	elimination rate constant	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour
Secondary	Pharmacokinetic assessment: T1/2	plasma elimination half-life	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour
Secondary	Pharmacokinetic assessment: %AUCextra	percentage of extrapolated AUCinf	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour
Secondary	Pharmacokinetic assessment: Cl/F	clearance	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour
Secondary	Pharmacokinetic assessment: Vd/F	volume of distribution	0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour