A Three Part, First-in-human, Randomized, Double-masked, Placebo-Controlled, Safety, Tolerability and Early Efficacy Study of MGV354 in Healthy Subjects and in Patients With Ocular Hypertension or Glaucoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 191
- 主要终点
- Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8
研究概览
简要总结
The purpose of this study is to determine if the clinical profile of topical-ocular MGV354 merits further development for the indication of lowering intraocular pressure (IOP).
详细描述
Part 1 will evaluate the safety and tolerability of single ascending doses of MGV354 compared to placebo in healthy male and female subjects. Part 2 will evaluate the safety and tolerability of MGV354 in a multiple ascending dose design (two highest tolerated doses from Part 1) compared to placebo when administered for 7 days to patients with ocular hypertension or glaucoma. Part 3 will explore the safety, tolerability and efficacy of a single dose level of MGV354 (maximum tolerated dose) compared to placebo when administered for 7 days in patients with ocular hypertension or glaucoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Documented informed consent.
- •Part 1: 18 to 70 years of age;
- •Parts 2 and 3: 18 years of age or older;
- •Able to communicate well with the investigator and understand and comply with the requirements of the study;
- •Body Mass Index (BMI) between 18 and 39;
- •In case of contact lens wear, willing to remove lenses 30 minutes before the first assessment until the end of the study. Corrective spectacles may be worn as needed.
- •Sitting vital signs (systolic and diastolic blood pressure and pulse rate) within normal ranges as specified in the protocol;
- •Part 1 (Healthy Volunteers): In good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- •Parts 2 and 3 (Patients): Diagnosed with open-angle glaucoma or confirmed ocular hypertension; mean IOP measurements in at least one eye after washout as specified in the protocol
- •Other protocol-specified inclusion criteria may apply.
- •Exclusion criteria:
- •History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes;
- •History of or current presence of clinically significant ECG abnormalities or arrhythmias;
- •History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical or breast cancer), treated or untreated, within the past 5 years;
- •Known clinical history of heart failure, myocardial infarction, or stroke;
- •Exposure during the four weeks preceding the Screening visit to any topical, inhaled, or systemic corticosteroids;
- •Angle grade less than Grade 2 in either eye;
- •Any abnormality, including corneal thickness > 620 microns, preventing reliable applanation tonometry;
- •Pregnant or lactating women and women of child-bearing potential;
- •Sexually active males must agree to use a condom during intercourse while taking drug and for 6 days after stopping MGV354 medication and should not father a child in this period;
- •Positive HIV, Hepatitis B Ag or Hepatitis C Ab test result at Screening;
- •Abnormal liver function tests;
- •History or presence of impaired renal function;
- •Part 1 (Healthy Volunteers): Use of any NEW prescription drugs or herbal supplements within four (4) weeks prior to initial dosing, and/or NEW over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing.
- •Parts 2 and 3 (Patients): Patients with related disease condition(s) including any form of glaucoma other than open-angle glaucoma and pseudoexfoliation and/or pigment dispersion components; patients who cannot safely discontinue use of all topical ocular and/or systemic IOP-lowering medication according to protocol-specified Washout Schedule; patients with ocular diseases or conditions as specified in the protocol; patients taking certain medications as specified in the protocol;
- •Other protocol-specified exclusion criteria may apply.
排除标准
- 未提供
研究组 & 干预措施
MGV354
Part 3: MGV354 ophthalmic suspension, 1 drop in both eyes once per day for 7 days
干预措施: MGV354 ophthalmic suspension (Drug)
Placebo
Part 3: MGV354 placebo, 1 drop in both eyes once per day for 7 days
干预措施: MGV354 placebo (Drug)
结局指标
主要结局
Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8
时间窗: Baseline, Day 8
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the five time points measured (8 AM, 10 AM, noon, 4 PM, and 8 PM). Baseline diurnal IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8 and averaging the available changes. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM
时间窗: Baseline, Day 8
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Baseline IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
次要结局
- Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration(Baseline, up to Day 9)
- Part 1: Maximum Observed Concentration [Cmax (ng/mL)](Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose)
- Part 1: Time to Reach Maximum Concentration [Tmax (h)](Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose)
- Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)](Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose)
- Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to 120 Hours Post Dose [AUC0-120 (ng*h/mL)](Pre-dose to 120 hours post-dose)
- Part 1: Area Under the Concentration-time Curve From 0 to Infinity [AUCinf (ng*h/mL)](Pre-dose to 120 hours post-dose)
- Part 1: Terminal Elimination Half-life [t1/2 (h)](Pre-dose to 120 hours post-dose)
- Part 2: Maximum Observed Concentration [Cmax (ng/mL)](Up to Day 7)
- Part 2: Time to Reach Maximum Concentration [Tmax (h)](Up to Day 7)
- Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)](Up to Day 7)
- Part 2: Accumulation Ratio (Racc)(Day 7)
- Part 3: Observed Concentration at 12 Hours Following Drug Administration [C12 (ng/mL)](Up to Day 8)