A phase 2b double-masked, randomized, active-controlled, dose-response study assessing the safety and ocular hypotensive efficacy of AR-12286 in patients with elevated intraocular pressure for 3 months
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 195
- 试验地点
- 6
- 主要终点
- The primary efficacy outcome will be the mean IOP across subjects within treatment group.
研究概览
简要总结
Title of the study: A phase 2b double-masked, randomized, active-controlled, dose-response study assessing the safety and ocular hypotensive efficacy of AR-xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" /12286 in patients with elevated intraocular pressure for 3 months.xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /
Research Hypothesis: AR-12286 Ophthalmic Solution 0.5%, or 0.7% (q.d., PM) or timolol maleate Ophthalmic Solution, 0.5% (b.i.d.) will be administered to both eyes for 3 months. The null hypothesis is that the ocular hypotensive efficacy of each concentration of AR-12286 ophthalmic solution is inferior to that of a positive control. The alternative hypothesis is that the ocular hypotensive efficacy of each concentration of AR-12286 is not inferior to that of a positive control, using a non-inferiority limit of -1.5mm Hg. With a sample size of 65-70 in each group, each pair wise comparison of test to control will have >80% power to conclude non-inferiority assuming a common standard deviation of 3.5 mm Hg and using one-sided 95% confidence interval around the difference (control – test) in IOP.
Primary objective:
To evaluate the ocular hypotensive efficacy of 2 doses of AR-12286.
Secondary Objective:
To evaluate the ocular and systemic safety of 2 doses of AR-12286.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •1.18 year of age or greater.
- •2.Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT).
- •3.Unmedicated (post-washout) IOP greater than or equal to 24 mm Hg at 2 eligibility visits (0800 hr), 2-7 days apart, and greater than or equal to 22 mm Hg at 1000 and 1600 hrs at the second qualification visit.
- •If only one eye meets the IOP criteria it must be the same eye that met the criteria at all the qualification timepoints.
- •4.Corrected visual acuity in each eye +1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200).
- •5.Able and willing to give signed informed consent and follow study instructions.
排除标准
- •Ophthalmic 1.Glaucoma: pseudoexfoliation or pigment dispersion component, history of angle closure or narrow angles.
- •Note: Previous laser peripheral iridotomy is NOT acceptable.
- •2.IOP greater than 36 mm Hg 3.Current use of more than 1 ocular hypotensive medications (Note: fixed dose combinations are considered multiple medications).
- •4.Known hypersensitivity to any component of the formulation (benzalkonium chloride, etc.), or to topical anesthetics.
- •5.Previous glaucoma intraocular surgery or glaucoma laser procedures in study eye(s).
- •6.Refractive surgery in study eye(s) (e.g., radial keratotomy, PRK, LASIK, etc.).
- •7.Ocular trauma within the past six months, or ocular surgery or laser treatment within the past three months.
- •8.Evidence of ocular infection, inflammation, clinically significant blepharitis or conjunctivitis at baseline (Visit 1), or a history of herpes simplex keratitis 9.Ocular medication of any kind within 30 days of Visit 1, with the exception of a) ocular hypotensive medications (which must be washed out according to the provided schedule), b) lid scrubs (which may be used prior to, but not after Visit 1) or c) lubricating drops for dry eye (which may be used throughout the study).
- •10.Clinically significant ocular disease (e.g. uveitis, severe keratoconjunctivitis sicca) which might interfere with the study, including glaucomatous damage so severe that washout of ocular hypotensive medications for one month is not judged safe.
- •11.Central corneal thickness greater than 600 µm.
- •12.Any abnormality preventing reliable applanation tonometry of either eye.
- •Systemic: 13.Clinically significant abnormalities (as determined by the treating physician) in laboratory tests at screening.
- •14.Known hypersensitivity or contraindication to Beta adrenoceptor antagonists including chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood pressure or heart rate; second or third degree heart block or congestive heart failure; severe diabetes).
- •15.Clinically significant systemic disease (e.g., myasthenia gravis, hepatic, renal, endocrine or cardiovascular disorders) which might interfere with the study.
- •17.Changes of systemic medication that could have a substantial effect on IOP within 30 days prior to screening, or anticipated during the study.
- •18.Due to the current status of the preclinical safety program, women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.
- •An adult woman is considered to be of childbearing potential unless she is one year post-menopausal or three months post-surgical sterilization.
- •All females of childbearing potential must have a negative urine pregnancy test result at the screening examination and must not intend to become pregnant during the study.
结局指标
主要结局
The primary efficacy outcome will be the mean IOP across subjects within treatment group.
时间窗: Timepoints of measuring primary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).
次要结局
- Mean diurnal IOP on month 3.(Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).)
- Mean percent change from diurnally adjusted baseline IOP at each post-dose timepoint of month 3(Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).)
- Mean change from diurnally adjusted baseline IOP at each post-dose timepoint of month 3(Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).)
- Mean change from the baseline mean diurnal IOP on month 3(Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).)
- An additional analysis of within treatment group paired tests with baseline will be performed using a paired t-test at each post-dose timepoint(Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).)