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The study is a single center, double-blind, randomized, parallel group, multiple ascending dose study in 16 healthy male volunteers. Subjects will receive multiple eye drop doses during 14 days of the treatment (HL217 or placebo according to the randomization). There will be 2 cohorts of 8 subjects (6 HL217 vs 2 placebo) receiving the following doses:
The purpose of this study is to evaluate the safety and tolerability of HL217 after multiple eye drop administrations at different doses in healthy subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: HL217 Ophathalmic Solution BID | Experimental | Low dose: two drops of 3 mg/mL of the treatment in one eye twice a day |
|
| Cohort 2: HL217 Ophathalmic Solution QID | Experimental | High dose: two drops of 3 mg/mL of the treatment in one eye 4 times a day |
|
| Placebo Ophathalmic Solution | Placebo Comparator | Placebo: two drops of placebo in one eye twice a day or 4 times a day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cohort 1: HL217 Ophathalmic Solution BID | Drug | Two drops of 3 mg/mL of the treatment in one eye twice a day |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Day 1 (Pre-dose) to Day 22 (End of study visit) |
| Clinical parameter: Physical examination | Physical examination recorded during the study will be individually listed and quantitative parameters will be summarized by using descriptive statistics | Day -1, Day 1 (Before administration, 4h, 8h, 12h), Day 2 (24h), Day 3 to 15, Day 22 (End of study visit) |
| Clinical parameter: Vital signs | Vital signs recorded during the study will be individually listed and quantitative parameters will be summarized by using descriptive statistics | Day -1, Day 1 (Before administration, 4h, 8h, 12h), Day 2 (24h), Day 3 to 15, Day 22 (End of study visit) |
| Clinical parameter: ECG (ElectroCardioGram) | ECG recorded during the study will be individually listed and quantitative parameters will be summarized by using descriptive statistics | Day -1, Day 1 (Before administration), Day 2, Day 15, Day 22 (End of study visit) |
| Clinical parameter: Laboratory parameters | All laboratory values recorded during the study will be individually listed and flagged for values outside reference ranges and for clinical relevance (assessed by investigator) | Day -1, Day 2, Day 15, Day 22 (End of study visit) |
| Local tolerance test | Redness, tingling and others should be checked |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic assessments: Cmax | observed maximum plasma concentration of HL217 | 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |
| Pharmacokinetic assessments: Tmax |
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Inclusion Criteria:
Healthy male subject, aged between 18 and 50 years inclusive
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
Body weight ≥ 50 kg and BMI between 18 and 30 kg/m²
Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination) including complete ocular examination
Normal Blood Pressure (BP) and Heart Rate (HR) after 10 minutes in supine position:
Normal ECG recording on a 12-lead ECG:
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
Normal dietary habits
Signing a written informed consent prior to selection
Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yves Donazzolo, M.D | Eurofins Optimed | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eurofins OPTIMED | Gières | France |
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| Cohort 2: HL217 Ophathalmic Solution QID | Drug | Two drops of 3 mg/mL of the treatment in one eye 4 times a day |
|
|
| Placebo | Drug | Placebo eye drops |
|
| Day -1, Day 1 (Before administration, 4h, 8h, 12h), Day 2 (24h), Day 3 to 15, Day 22 (End of study visit) |
first time to reach Cmax |
| 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |
| Pharmacokinetic assessments: AUCt | area under the plasma concentration curve from administration up to the last quantifiable concentration at time t | 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |
| Pharmacokinetic assessments: AUCinf | area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase | 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |
| Pharmacokinetic assessments: Kel | elimination rate constant | 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |
| Pharmacokinetic assessments: t1/2 | plasma elimination half-life | 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |
| Pharmacokinetic assessments: %AUCextra | percentage of extrapolated AUCinf | 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |
| Pharmacokinetic assessments: Vd/F | volume of distribution | 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |
| Pharmacokinetic assessments: CL/F | Clearance | 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 |