A Randomized, Multi-Center, Parallel-Group, Safety and Efficacy Study of Lotemax® Gel 0.5% and Restasis 0.05% for 12 Weeks in Subjects With Mild or Moderate Keratoconjunctivitis Sicca (Dry Eye Disease; DED)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Adverse Events (AEs)
研究概览
简要总结
This study is being conducted to investigate the safety, comfort, and tolerability of 3 treatments: loteprednol etabonate ophthalmic (Lotemax®) gel 0.5 percent (%) administered twice daily (BID) with or without cyclosporine ophthalmic emulsion (Restasis) 0.05% administered BID, and Restasis 0.05% treatment alone for 12 weeks and at a follow-up safety visit 1 week post-treatment. This study will also investigate the relative efficacy of Lotemax gel 0.5% administered BID with or without Restasis 0.05% treatment administered BID and of Restasis 0.05% treatment alone for the reduction of clinical signs or symptoms of keratoconjunctivitis sicca (DED) over the first 4 weeks of a 12-week treatment period and at the end of a 12-week treatment period.
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
- Single (Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have been diagnosed with or treated for keratoconjunctivitis sicca (DED) within 6 months prior to screening visit (Day -14).
- •Have a baseline intraocular pressure (IOP) measurement of greater than or equal to (≥) 5 millimeters of mercury (mmHg) and less than or equal to (≤) 22 mmHg in each eye, with or without anti-glaucoma therapy.
- •Have mild to moderate DED in 1 eye or both eyes at screening visit (Day -14) and randomization visit (Day 0).
排除标准
- •Have a known hypersensitivity to corticosteroids, cyclosporine, fluorescein, lissamine green, topical anesthetic, or any component of either of the study drugs.
- •Have severe DED.
- •Have corneal erosive disease or other conditions suggestive of extensive damage of the cornea.
- •Have a history of elevated IOP, a history of glaucoma, or IOP greater than (>) 22 mmHg in either eye at the screening visit (Day -14).
- •Have had penetrating intraocular surgery in the past 12 months or require penetrating intraocular surgery during the study.
- •Have had eyelid surgery within the 6 months prior to Visit 1 (Day -14) or have DED secondary to surgery.
- •Have visible evidence of anterior lid Demodex spp. infection or infestation.
- •Have had corneal refractive surgery or corneal transplantation.
- •Have congenitally absent lacrimal or meibomian glands or have any obstructive disease of the lacrimal glands, sarcoidosis, or any other lacrimal gland deficiency.
- •Have a diagnosis of on-going ocular infection, active anterior blepharitis, moderate to severe pinguecula, Stevens-Johnson syndrome, ocular cicatricial pemphigoid, significant conjunctival scarring, ocular chemical burn, or ocular neurotrophic keratitis.
- •Have any serious systemic disease or uncontrolled medical condition that in the judgment of the investigator could confound study assessments or limit compliance.
- •Have a history of ocular herpetic keratitis or have had active blepharitis in the 4 weeks prior to the first dose.
- •Have had ocular surgery (including laser) within 6 months prior to the first Treatment Period, or plan or require ocular surgery during the study. Neodymiumdoped:yttrium aluminum garnet (Nd:YAG) laser posterior capsulotomy is allowed.
研究组 & 干预措施
Lotemax Gel 0.5% and Restasis 0.05%
Participants will administer lotemax gel 0.5 % BID in both eyes (OU) for 2 weeks, then administer both lotemax gel 0.5% and restasis emulsion 0.05% BID OU for 2 weeks, then administer restasis emulsion 0.05% BID OU for 8 weeks. Participants will also receive preservative-free Soothe Lubricant Eye Drops as needed (up to 4 times per day).
干预措施: Lotemax (Drug)
Lotemax Gel 0.5% and Restasis 0.05%
Participants will administer lotemax gel 0.5 % BID in both eyes (OU) for 2 weeks, then administer both lotemax gel 0.5% and restasis emulsion 0.05% BID OU for 2 weeks, then administer restasis emulsion 0.05% BID OU for 8 weeks. Participants will also receive preservative-free Soothe Lubricant Eye Drops as needed (up to 4 times per day).
干预措施: Restasis (Drug)
Lotemax Gel 0.5% and Restasis 0.05%
Participants will administer lotemax gel 0.5 % BID in both eyes (OU) for 2 weeks, then administer both lotemax gel 0.5% and restasis emulsion 0.05% BID OU for 2 weeks, then administer restasis emulsion 0.05% BID OU for 8 weeks. Participants will also receive preservative-free Soothe Lubricant Eye Drops as needed (up to 4 times per day).
干预措施: Soothe® Lubricant Eye Drops (Drug)
Lotemax Gel 0.5%
Participants will administer lotemax gel 0.5% BID OU for 12 weeks. Participants will also receive preservative-free Soothe Lubricant Eye Drops as needed (up to 4 times per day).
干预措施: Lotemax (Drug)
Lotemax Gel 0.5%
Participants will administer lotemax gel 0.5% BID OU for 12 weeks. Participants will also receive preservative-free Soothe Lubricant Eye Drops as needed (up to 4 times per day).
干预措施: Soothe® Lubricant Eye Drops (Drug)
Restasis 0.05%
Participants will administer restasis emulsion 0.05% BID OU for 12 weeks. Participants will also receive preservative-free Soothe Lubricant Eye Drops as needed (up to 4 times per day).
干预措施: Restasis (Drug)
Restasis 0.05%
Participants will administer restasis emulsion 0.05% BID OU for 12 weeks. Participants will also receive preservative-free Soothe Lubricant Eye Drops as needed (up to 4 times per day).
干预措施: Soothe® Lubricant Eye Drops (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs)
时间窗: Baseline up to Week 13
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Change From Baseline in Corneal Total Fluorescein Staining Score at for the Study Eye at Week 4
时间窗: Baseline (Day 0), Week 4
Fluorescein Corneal Staining indicates the damage to the corneal epithelium (corneal epitheliopathy). Punctate corneal staining with fluorescein was evaluated and graded according to the National Eye Institute (NEI) grading method. The cornea was divided into 5 regions: central, superior, inferior, nasal and temporal. Each of these 5 regions was graded from scores 0 to 3, where 0 indicated no staining (absent) and 3 maximal staining (severe damage). The total score was the sum of all these regions, ranged from 0 (absence of corneal epitheliopathy) to 15 (severe corneal epitheliopathy).
Change From Baseline in Mean Ocular Surface Disease Index (OSDI) Questionnaire Total Score at Week 4
时间窗: Baseline, Week 4
OSDI is a 12-item questionnaire developed to assess severity of DED. There are 3 question types: "Have you experienced any of following (light sensitivity, eye feel gritty, sore eyes, blurred vision, and poor vision) during last week?"(items 1-5); "Have problems with your eyes limited you in performing any of following (reading, driving at night, working with computer, and watching TV) during last week?" (items 6-9); and "Have your eyes felt uncomfortable in any of following situations (windy, low humidity, air conditioned) during the last week?" (items 10-12). Response of each of these questions were graded on a scale (that relate to the frequency of ocular surface disease effects) of 0 (none of the time) to 4 (all of the time).Total OSDI score was calculated using following formula: OSDI=(\[sum of scores for all questions answered\] × 100)/(\[total number of questions answered\] \* 4). Total OSDI score ranged from 0 to 100, with higher scores representing greater disability.
Mean Grade for Participant-Reported Post-Dosing Ocular Comfort Values
时间窗: Week 12
Participants scored their degree of comfort with their assigned study drug on a 4-point scale (0-3 units) within 5 minutes after instillation of study drug. Comfort grade 0 indicated comfortable, discomfort absent; 1 indicated generally comfortable, mild discomfort; 2 indicated some discomfort but tolerable, moderate discomfort; 3 indicated severely uncomfortable or intolerable. The mean global ocular comfort grade was reported.
次要结局
- Number of Participants With Overall Change From Baseline in Dry Symptoms at Week 12 as Assessed Independently by Investigators and Participants(Baseline, Week 12)
- Change From Baseline in Mean OSDI Questionnaire Total Score and Individual Question Scores at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Corneal Total Fluorescein Staining Score for the Study Eye and Averaged for Both Eyes at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Total Combined Lissamine Green (LG) Staining (Nasal Plus Temporal Conjunctival) Score for the Study Eye and Averaged for Both Eyes at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Tear Osmolarity of Participant Worst Eye Value at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Eye Dryness Questionnaire Total and Individual Question Scores at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Tear Film Breakup Time (TFBUT) (by Fluorescein Staining) of the Study Eye and Averaged for Both Eyes of a Participant at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Value of Participant Worst Eye Score for Each Symptom (Including the Pre-Specified Worst Symptom) in the List of Possible Worst Symptoms at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Tear Osmolarity Between Two Eyes of Participant at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Eye Comfort Index Questionnaire Total Score and Individual Question Scores at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Non-Invasive Keratographic Tear Film Breakup Time (NIKBUT) of the Study Eye and Averaged for Both Eyes of a Participant at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Anesthetized Schirmer's Test Values (Distance of Strips Wetting) in the Study Eye and Averaged for Both Eyes of a Participant at Week 13(Baseline, Week 13)
- Averaged Daily Soothe Lubricant Eye Drops Usage(Baseline up to Week 12)
- Change From Baseline in Ocular Redness Score for Study Eye and Averaged for Both Eyes at Week 12, as Assessed by Investigator(Baseline, Week 12)
- Change From Baseline in Non-Invasive Keratographic Limbal and Bulbar Ocular Redness Scores for Study Eye and Averaged for Both Eyes at Week 12, as Assessed by Investigator(Baseline, Week 12)