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A Dose-escalation Clinical Trial After Multiple Dosing of HL217 Eye Drop in Healthy Male Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03648346
Recruitment Status : Completed
First Posted : August 27, 2018
Last Update Posted : March 29, 2019
Sponsor:
Information provided by (Responsible Party):
Hanlim Pharm. Co., Ltd.

Brief Summary:

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:

  • Cohort 1 : two drops of 3 mg/mL of the treatment in one eye twice a day (low dose),
  • Cohort 2 : two drops of 3 mg/mL of the treatment in one eye 4 times a day (high dose).

Condition or disease Intervention/treatment Phase
Healthy Subjects Drug: Cohort 1: HL217 Ophathalmic Solution BID Drug: Cohort 2: HL217 Ophathalmic Solution QID Drug: Placebo Phase 1

Detailed Description:
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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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Dose Block-randomized, Double Blind, Placebo Controlled, Dose-escalation Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics After Multiple Dosing of HL217 Eye Drop in Healthy Male Subjects
Actual Study Start Date : April 4, 2018
Actual Primary Completion Date : July 25, 2018
Actual Study Completion Date : January 25, 2019

Arm Intervention/treatment
Experimental: Cohort 1: HL217 Ophathalmic Solution BID
Low dose: two drops of 3 mg/mL of the treatment in one eye twice a day
Drug: Cohort 1: HL217 Ophathalmic Solution BID
Two drops of 3 mg/mL of the treatment in one eye twice a day
Other Name: 3mg/mL

Experimental: Cohort 2: HL217 Ophathalmic Solution QID
High dose: two drops of 3 mg/mL of the treatment in one eye 4 times a day
Drug: Cohort 2: HL217 Ophathalmic Solution QID
Two drops of 3 mg/mL of the treatment in one eye 4 times a day
Other Name: 3mg/mL

Placebo Comparator: Placebo Ophathalmic Solution
Placebo: two drops of placebo in one eye twice a day or 4 times a day
Drug: Placebo
Placebo eye drops




Primary Outcome Measures :
  1. Clinical parameter: Adverse Events (AE) [ Time Frame: Day 1 (Pre-dose) to Day 22 (End of study visit) ]
    AEs will be coded according to the MedDRA. They will be classified into pre-defined standard categories according to chronological criteria

  2. Clinical parameter: Physical examination [ Time Frame: Day -1, Day 1 (Before administration, 4h, 8h, 12h), Day 2 (24h), Day 3 to 15, Day 22 (End of study visit) ]
    Physical examination recorded during the study will be individually listed and quantitative parameters will be summarized by using descriptive statistics

  3. Clinical parameter: Vital signs [ Time Frame: Day -1, Day 1 (Before administration, 4h, 8h, 12h), Day 2 (24h), Day 3 to 15, Day 22 (End of study visit) ]
    Vital signs recorded during the study will be individually listed and quantitative parameters will be summarized by using descriptive statistics

  4. Clinical parameter: ECG (ElectroCardioGram) [ Time Frame: Day -1, Day 1 (Before administration), Day 2, Day 15, Day 22 (End of study visit) ]
    ECG recorded during the study will be individually listed and quantitative parameters will be summarized by using descriptive statistics

  5. Clinical parameter: Laboratory parameters [ Time Frame: Day -1, Day 2, Day 15, Day 22 (End of study visit) ]
    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)

  6. Local tolerance test [ Time Frame: Day -1, Day 1 (Before administration, 4h, 8h, 12h), Day 2 (24h), Day 3 to 15, Day 22 (End of study visit) ]
    Redness, tingling and others should be checked


Secondary Outcome Measures :
  1. Pharmacokinetic assessments: Cmax [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    observed maximum plasma concentration of HL217

  2. Pharmacokinetic assessments: Tmax [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    first time to reach Cmax

  3. Pharmacokinetic assessments: AUCt [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    area under the plasma concentration curve from administration up to the last quantifiable concentration at time t

  4. Pharmacokinetic assessments: AUCinf [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase

  5. Pharmacokinetic assessments: Kel [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    elimination rate constant

  6. Pharmacokinetic assessments: t1/2 [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    plasma elimination half-life

  7. Pharmacokinetic assessments: %AUCextra [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    percentage of extrapolated AUCinf

  8. Pharmacokinetic assessments: Vd/F [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    volume of distribution

  9. Pharmacokinetic assessments: CL/F [ Time Frame: 0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14 ]
    Clearance



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  10. Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.

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 possibility of contact 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 > 30 grams / day);
  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 an allergy to Fluorescein
  18. Subjects with previous participation in the current study
  19. Subject under administrative or legal supervision
  20. Subject who would receive more than 4500 euros as indemnities for his participation in biomedical research within the 12 last months, including the indemnities for the present study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03648346


Locations
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France
Eurofins OPTIMED
Gières, France
Sponsors and Collaborators
Hanlim Pharm. Co., Ltd.
Investigators
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Principal Investigator: Yves Donazzolo, M.D Eurofins Optimed

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Responsible Party: Hanlim Pharm. Co., Ltd.
ClinicalTrials.gov Identifier: NCT03648346    
Other Study ID Numbers: HL217-102
First Posted: August 27, 2018    Key Record Dates
Last Update Posted: March 29, 2019
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ophthalmic Solutions
Pharmaceutical Solutions