Healthy Subject
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability and PK parameters in healthy subjects.
Detailed 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.
Interventions
DRUGCohort 1: HL217 Ophathalmic Solution QD
Cohort 1 (Once a day)
DRUGCohort 2: HL217 Ophathalmic Solution BID
Cohort 2 (Twice a day)
DRUGCohort 3: HL217 Ophthalmic Solution QID
Cohort 3 (Four times a day)
DRUGPlacebo Ophthalmic solution
Placebo
Sponsors
Hanlim Pharm. Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical parameter: Adverse Events (AE) | During 72hours | AEs will be coded according to the MedDRA. They will be classified into pre-defined standard categories according to chronological criteria |
| Local tolerance: Redness, Tingling and Other ophthalmic adverse events | During 72hours | Redness, tingling and others should be checked |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic assessment: AUClast | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | area under the plasma concentration curve from administration up to the last quantifiable concentration at time 72h |
| Pharmacokinetic assessment: AUCinf | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase |
| Pharmacokinetic assessment: Kel | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | elimination rate constant |
| Pharmacokinetic assessment: Cmax | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | observed maximum plasma concentration of HL217 |
| Pharmacokinetic assessment: %AUCextra | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | percentage of extrapolated AUCinf |
| Pharmacokinetic assessment: Cl/F | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | clearance |
| Pharmacokinetic assessment: Vd/F | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | volume of distribution |
| Pharmacokinetic assessment: T1/2 | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | plasma elimination half-life |
| Pharmacokinetic assessment: Tmax | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | first time to reach Cmax |
Outcome results
None listed