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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Local tolerance test
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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:
- •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;
- •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;
- •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.
排除标准
- •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
- •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)
- •Subjects with an allergy to Fluorescein
- •Subjects with previous participation in the current study
- •Subject under administrative or legal supervision
- •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
研究组 & 干预措施
Placebo Ophathalmic Solution
Placebo: two drops of placebo in one eye twice a day or 4 times a day
干预措施: Placebo (Drug)
结局指标
主要结局
Local tolerance test
时间窗: 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
Clinical parameter: Adverse Events (AE)
时间窗: 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
Clinical parameter: Physical examination
时间窗: 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
Clinical parameter: Vital signs
时间窗: 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
Clinical parameter: ECG (ElectroCardioGram)
时间窗: 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
Clinical parameter: Laboratory parameters
时间窗: 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)
次要结局
- 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: t1/2(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: 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: Kel(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(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(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: 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(0h, 12h, 12h05min, 12h15min, 12h30min, 12h45min, 13h, 14h, 15h, 16h, 18h, 20h, 24h, 28h and 32hours after the last administration at Day 14)