NCT02622334已完成1 期
A MULTIPLE-CENTER, INVESTIGATOR/SUBJECT MASKED, ADAPTIVE, MULTIPLE ASCENDING DOSE, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF RO5093151 FOLLOWING 7 DAYS ADMINISTRATION IN PATIENTS WITH PRIMARY OPEN ANGLE GLAUCOMA OR OCULAR HYPERTENSION
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 7
- 主要终点
- Changes in vital signs, electrocardiogram (ECG), opthalmologic assessments, and clinical laboratory results
研究概览
简要总结
The purpose of the study is to assess the safety, tolerability, and IOP effects of RO5093151 following 7 days of topical ocular treatment in patients with primary open angle glaucoma or ocular hypertension.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- 否
入选标准
- •Diagnosis of ocular hypertension (OHT) or primary open angle glaucoma (POAG) in at least one eye (qualifying eye) as determined by the Investigator at screening or based on a reliable and documented assessment done within the last 6 months prior to screening provided that no progression of visual field damage is expected
- •At baseline visit, intraocular pressure (IOP) >= 24 mmHg in the morning and >= 21 mmHg in the afternoon measurement in at least one eye (qualifying eye = study eye) and =< 34 mmHg at all time points in both eyes
- •Best corrected logMAR visual acuity score of 0.7 (20/100 Snellen) or better in each eye as measured by ETDRS visual acuity test at screening
- •Central corneal pachymetry measurement 420 to 620 micrometer in qualifying eye at screening
- •Cup-to-disk ratio =< 0.8 (both eyes) at screening
- •Anterior chamber angle is open and non-occludable as confirmed by the Investigator by gonioscopy examination at screening
排除标准
- •History of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease (multiple allergies, seasonal allergy is acceptable), metabolic disorder, cancer or cirrhosis
- •Uncontrolled hypertension (SBP >= 160 mmHg and/or DBP >= 100 mmHg) despite treatment at the time of screening confirmed by the average of >= 3 blood pressure measurements, properly measured with well-maintained equipment
- •Clinically significant abnormalities in laboratory test results at screening
- •Hypersensitivity to RO5093151 or any of the components of its formulation, or hypersensitivity to latanoprost or any of the components of its formulation (Part B only)
- •Donation of blood over 500 mL within three months prior to screening
- •Positive result on hepatitis B (HBV), hepatitis C (HCV), or HIV 1 and 2
- •Presence of narrow angle (=< grade 2 Shaffer gonioscopic classification) or complete or partial closure, as measured by gonioscopy or at risk for angle closure as assessed by the Investigator
- •Other forms of glaucoma than POAG or OHT in the study eye
- •Any abnormality preventing reliable applanation tonometry
- •Any clinically significant corneal scarring, haze or opacity
- •Patient uncooperativeness that restricts adequate examination of IOP, ocular fundus or anterior chamber
- •Evidence of clinically significant blepharitis, concurrent infectious/non-infectious conjunctivitis, keratitis or uveitis
- •History or signs of penetrating ocular trauma. Uneventful (uncomplicated) cataract surgery performed 3 months prior to screening is allowed
- •According to the Investigator's best judgment, risk of visual field or visual acuity worsening in either eye as a consequence of glaucoma progression or consequence of participation in the trial (i.e., during washout of ocular hypotensive medications or treatment with placebo) or any other ocular disease
- •Unable to safely stop ocular hypotension medications prior to randomization according to the required minimum washout periods
- •History of any ocular filtering surgical intervention, previous glaucoma intraocular surgery, or laser trabeculoplasty
- •History of refractive surgery (laser assisted in-situ keratomileusis, laser epithelial keratomileusis, photorefractive keratectomy, phototherapeutic keratectomy)
- •Any other intraocular surgery within 6 months of screening
- •Advanced age-related macular degeneration (wet or dry), vitreous hemorrhage, diabetic retinopathy or any progressive retinal or optic nerve disease from any cause other than glaucoma
研究组 & 干预措施
Part A
Experimental
Participants will receive up to 3 multiple ascending dose levels with the starting dose of 0.1% RO5093151 (topical ocular instillation) and sequentially 0.5% and 1% RO5093151 doses or placebo (3:1, active:placebo) twice a day (BID) on Day 1 and once a day (QD) for 6 days.
干预措施: Placebo (Drug)
Part A
Experimental
Participants will receive up to 3 multiple ascending dose levels with the starting dose of 0.1% RO5093151 (topical ocular instillation) and sequentially 0.5% and 1% RO5093151 doses or placebo (3:1, active:placebo) twice a day (BID) on Day 1 and once a day (QD) for 6 days.
干预措施: RO5093151 (Drug)
Part B
Experimental
Participants will receive highest feasible dose (HFD) or maximum tolerated dose (MTD) of RO5093151 from Part A or 0.005% latanoprost (topical ocular instillation) once daily for 7 days.
干预措施: Latanoprost (Drug)
Part B
Experimental
Participants will receive highest feasible dose (HFD) or maximum tolerated dose (MTD) of RO5093151 from Part A or 0.005% latanoprost (topical ocular instillation) once daily for 7 days.
干预措施: RO5093151 (Drug)
结局指标
主要结局
Changes in vital signs, electrocardiogram (ECG), opthalmologic assessments, and clinical laboratory results
时间窗: Up to 12 weeks
Incidence of adverse events
时间窗: Up to 12 weeks
Change in mean IOP after 7 days treatment vs baseline: change from baseline for RO5093151 and latanoprost and difference in change from baseline between RO5093151 and latanoprost
时间窗: Baseline (Day 1) and Day 8
次要结局
- Maximum observed plasma concentration (Cmax)(Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose)
- Time to maximum observed plasma concentration (Tmax)(Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose)
- Concentration at the end of a dosing interval before the next dose administration (Ctrough)(Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose)
- Area under the plasma concentration versus time curve from zero to 24 h post-dose (AUC0-24)(Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose)
- Change in IOP at matched clock-times after 7 days of treatment vs baseline (diurnal IOP) and between RO5093151 and latanoprost(Baseline and Day 8)
- Area under the plasma concentration versus time curve up to the last measurable concentration (AUClast)(Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose)
- Apparent terminal half-life (T1/2)(Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose)
研究者
研究点 (7)
Loading locations...
相似试验
已完成
1 期
A 2-Part Study to Evaluate the Safety of Supra-Therapeutic Doses of RO4602522 and to Investigate the Effect of RO4602522 on the QTc IntervalHealthy VolunteerNCT02104648Hoffmann-La Roche203
进行中（未招募）
不适用
Efficacy and Safety of Dose Redution of Radotinib as a First Line Treament in Ph+ CMLChronic Phase Ph+ Chronic Myeloid LeukemiaNCT06665412Il-Yang Pharm. Co., Ltd.169
终止
不适用
Safety and Effectiveness Assessment of the MakAir Artificial VentilatorAcute Respiratory Distress SyndromeNCT04475185Nantes University Hospital4
尚未招募
不适用
The Efficacy and Safety of the RCMOP Sequential Therapy as a First-line Treatment for Patients With Intermediate-to-high Risk Diffuse Large B-cell Lymphoma Who Had Incomplete Remission.Diffuse Large B-cell LymphomaNCT05990985The First Hospital of Jilin University20
终止
2 期
A Clinical Study to Assess the Safety and Activity of SRT501 Alone or in Combination With Bortezomib in Patients With Multiple MyelomaMultiple MyelomaNCT00920556Sirtris, a GSK Company24