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

NCT03648346 | Completed Phase 1

• 1 other identifier: HL217-102
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (6)

• 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

  Day -1, Day 1 (Before administration, 4h, 8h, 12h), Day 2 (24h), Day 3 to 15, Day 22 (End of study visit)

Secondary Outcomes (9)

• Pharmacokinetic assessments: 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: Tmax

  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

  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

  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

  0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14

Study Arms (3)

Cohort 1: HL217 Ophathalmic Solution BID

EXPERIMENTAL

Low dose: two drops of 3 mg/mL of the treatment in one eye twice a day

Drug: Cohort 1: HL217 Ophathalmic Solution BID

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

Drug: Cohort 2: HL217 Ophathalmic Solution QID

Placebo Ophathalmic Solution

PLACEBO COMPARATOR

Placebo: two drops of placebo in one eye twice a day or 4 times a day

Drug: Placebo

Interventions

Cohort 1: HL217 Ophathalmic Solution BID DRUG

Two drops of 3 mg/mL of the treatment in one eye twice a day

Also known as: 3mg/mL

Cohort 1: HL217 Ophathalmic Solution BID

Cohort 2: HL217 Ophathalmic Solution QID DRUG

Two drops of 3 mg/mL of the treatment in one eye 4 times a day

Also known as: 3mg/mL

Cohort 2: HL217 Ophathalmic Solution QID

Placebo DRUG

Placebo eye drops

Placebo Ophathalmic Solution

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• mmHg ≤ Systolic Blood Pressure (SBP) ≤ 140 mmHg,
• mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 90 mmHg,
• bpm ≤ HR ≤ 100 bpm,
• Or considered NCs by investigators;
• Normal ECG recording on a 12-lead ECG:
• \< PR \< 200 ms,
• QRS \< 120 ms,
• QTcf ≤ 430 ms,
• No sign of any trouble of sinusal automatism,
• Or considered NCs by investigators;

You may not qualify if:

• Any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic, infectious or ocular disease
• Frequent headaches and / or migraine, recurrent nausea and / or vomiting
• 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
• Blood donation (including in the frame of a clinical trial) within 2 months before administration or apheresis within 20 days before administration
• General anaesthesia within 3 months before administration
• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician (including allergy to fluorescein)
• Inability to abstain from intensive muscular effort;
• No possibility of contact in case of emergency;
• 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
• Subjects who have taken drug metabolizing enzyme inducing agents and inhibitors such as barbitals within a month prior to the first administration
• History or presence of drug or alcohol abuse (alcohol consumption \> 30 grams / day);
• Excessive consumption of beverages with xanthine bases (\> 5 cups or glasses / day) and not able to stop 24h prior to admission until discharge
• Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2
• Major surgery (general or ocular) within 28 days prior to randomization or major surgery planned during the next 6 months
• 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

Sponsors & Collaborators

• Hanlim Pharm. Co., Ltd.: lead

Study Sites (1)

Eurofins OPTIMED

Gières, France

Location

Study Officials

• Yves Donazzolo, M.D

  Eurofins Optimed

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: August 27, 2018
• Study Start: April 4, 2018
• Primary Completion: July 25, 2018
• Study Completion: January 25, 2019
• Last Updated: March 29, 2019

Record last verified: 2018-08

Locations

FR (1)