Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model

SUMMARY

Background: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol*) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat?) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis.

Objective: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model.

Research design and methods: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3?min, 5?min, and 7?min post challenge. Objective redness and chemosis assessments were made at 10?min, 15?min, and 20?min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments.

Main outcome measures; results: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, –0.19 (?p = 0.003) and –0.52 (?p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis –0.24 (?p < 0.001), ciliary redness –0.55 (?p < 0.001), and episcleral redness –0.58 (?p < 0.001) than epinastine treated eyes.

Conclusion: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.

* Patanol is a registered tradename of Alcon Laboratories Inc, Forth Worth, TX, USA     

Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model

OBJECTIVE: To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge. RESEARCH DESIGN AND METHODS: The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0-4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27 min after topical drug administration, such that the first post-challenge assessment was made 30 min post-drug instillation. Allergic signs and symptoms were evaluated at 3 min, 10 min, and 20 min postchallenge and safety and efficacy analyses were performed. RESULTS: Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3 min and 10 min post-challenge (p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge (p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye. CONCLUSION: Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.     

Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model

SUMMARY

Objective: To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge.

Research design and methods: The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0–4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27?min after topical drug administration, such that the first post-challenge assessment was made 30?min post-drug instillation. Allergic signs and symptoms were evaluated at 3?min, 10?min, and 20?min post-challenge and safety and efficacy analyses were performed.

Results: Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3?min and 10?min post-challenge (?p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge (?p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye.

Conclusion: Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.     

Efficacy and comfort of olopatadine 0.2% versus epinastine 0.05% ophthalmic solution for treating itching and redness induced by conjunctival allergen challenge

ABSTRACT

Background: Olopatadine 0.2% (Pataday, Alcon Laboratories Inc., Fort Worth, Texas, USA) and epinastine 0.05% (Elestat, Inspire Pharmaceuticals, Inc., Durham, NC, USA) are topical ocular anti-allergic agents. Both are H₁ antihistamine/mast cell stabilizers indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Objective: To compare the efficacy and comfort of olopatadine 0.2% with epinastine 0.05%, in the prevention of ocular itching associated with allergic conjunctivitis following conjunctival allergen challenge (CAC).

Research design and methods: This was a 7 week, four visit, double-masked, randomized, placebo-controlled CAC study. Visit 1 screened subjects for positive ocular allergic responses and Visit 2 confirmed those responses. At Visit 3, 92 subjects were randomized into one of four treatment groups to receive one drop of study medication in each eye: (1) olopatadine 0.2%/placebo, (2) epinastine 0.05%/placebo, (3) olopatadine 0.2%/epinastine 0.05%, (4) placebo/placebo. Subjects were challenged 12?h after drop instillation to evaluate duration of action. At Visit 4, subjects were challenged 5?min after drop instillation to evaluate onset of action. Drop comfort was assessed at Visit 4.

Main outcome measures; results: This article focuses on the results of the onset-of-action challenge (Visit 4). At Visit 4, ocular itching was assessed at 3, 5, and 7?min and redness was assessed at 7, 15, and 20?min post-challenge. Drop comfort was assessed upon instillation, at 30?s, and at 1, 2, and 5?min post-instillation. Olopatadine 0.2%-treated eyes exhibited significantly lower mean ocular itching scores versus epinastine 0.05%-treated eyes at 5 (?p = 0.024) and 7?min (?p = 0.003) post-challenge. Olopatadine 0.2%-treated eyes exhibited significantly lower mean redness scores versus epinastine 0.05%-treated eyes at all time points post-challenge (ciliary: p ≤ 0.013, conjunctival: p ≤ 0.015, episcleral: p ≤ 0.006). Olopatadine 0.2% was rated as significantly more comfortable than epinastine 0.05% at 1?min post-drop instillation (?p = 0.003). All adverse events were non-serious and unrelated to study medication. Although the CAC model reproduces allergic responses that are not environmentally-induced, patients experience varying severities of responses as are seen in real-world situations.

Conclusion: Olopatadine 0.2% was superior to epinastine 0.05% in preventing ocular itching and redness at onset when induced by the CAC model.     

奥洛他定温度敏感眼用原位凝胶的制备

目的:研制奥洛他定温度敏感眼用原位凝胶。方法:采用泊洛沙姆P407和P188为温敏材料,以胶凝温度为指标,通过星点设计-效应面法优化处方。结果:经过优化筛选出的处方在室温条件下是自由流动的液体,在生理条件下发生胶凝形成凝胶。结论:所研制奥洛他定眼用温度敏感原位凝胶符合眼部应用要求,体现出良好的临床应用前景。     

Mast cell stabilization and anti-histamine effects of olopatadine ophthalmic solution: a review of pre-clinical and clinical research

BACKGROUND: Histamine receptor activation and degranulation of mast cells are the mechanisms by which the ocular itching, hyperemia, chemosis, eyelid swelling, and tearing of seasonal allergic conjunctivitis are induced. Some of the topical solutions available as anti-allergy therapies are intended to interfere with these mechanisms, and the body of research regarding the capabilities of these therapeutic molecules continues to expand. OBJECTIVE: To review the currently available literature regarding one topical ophthalmic anti-allergy agent, olopatadine (Patanol), and its anti-histaminic and mast cell stabilizing actions, both in pre-clinical and clinical settings. DESIGN AND METHODS: Relevant research of laboratory, animal model, and clinical trial studies performed using olopatadine was reviewed. MEDLINE literature searches were conducted and supplemented by additional reports which furthered relevant discussion or were necessary to verify the information resulting from original searches. RESULTS: Olopatadine demonstrates unique properties both pre-clinically and clinically which differentiate it from other therapeutic molecules in its class of dual action mast cell stabilizer/anti-histamine. Its non-perturbation of cell membranes, human conjunctival mast cell stabilization in vivo and in vitro, and superior efficacy as compared to other topical anti-allergic medications including mast cell stabilizers, anti-histamines, and dual action agents, all contribute to olopatadine's profile. CONCLUSIONS: Peer-reviewed literature suggests that olopatadine is clinically superior to the other anti-allergic molecules because of its strong anti-histaminic qualities and its unique ocular mast cell stabilizing properties.     

Evaluation of the effects of olopatadine ophthalmic solution, 0.2% on the ocular surface of patients with allergic conjunctivitis and dry eye*

ABSTRACT

Purpose: Olopatadine hydrochloride 0.2% (Pataday^?, Alcon, Fort Worth, USA) is a topical ocular anti-allergic agent that has shown high rates of efficacy in treating ocular itching, the primary symptom of allergic conjunctivitis, and allows for once-daily dosing. Since some patients suffer from signs or symptoms of dry eye in addition to ocular allergy, this study was designed to evaluate the safety of olopatadine 0.2% in a population of patients with both allergic conjunctivitis and dry eye.

Methods: This was a single-center, 3-visit, double-masked, randomized study. Fifty-two patients diagnosed with ocular allergy and mild-to-moderate dry eye were evaluated. After a run-in period, patients were randomized to receive either olopatadine hydrochloride 0.2% or a tear saline, and self-dosed once-daily for 1 week. Outcome measures included tear film break-up time, corneal and conjunctival staining, tear volume and flow as measured by fluorophotometry, Schirmer's test, injection, and symptom evaluations.

Results: No significant differences between the treatment groups were observed (?p > 0.05). No serious adverse events occurred during the trial. Variability in the presentation of dry eye can hinder the observation of treatment effects. Although the study design facilitated the comparison of olopatadine 0.2% against an agent that was certain to not exacerbate dry eye, future comparison of olopatadine 0.2% against other agents in its drug class would provide useful information about relative drug tolerabilities.

Conclusion: As there were no significant changes in the signs and symptoms of dry eye, olopatadine hydrochloride 0.2% is safe to use in ocular allergy patients with mild-to-moderate dry eye.     

奥洛他定治疗过敏性结膜炎临床观察

目的 观察奥洛他定治疗过敏性结膜炎的临床治疗效果.方法 将67例过敏性结膜炎患者,随机分为观察组(34例)和对照组(33例).观察组给予0.1％盐酸奥洛他定滴眼液,每眼1滴/次,2次/d.早晚各1次,眼用;对照组给予2％色甘酸钠滴眼液,每眼1滴/次,4次/d,眼用.均治疗7d.观察两组治疗后1h、7d、30 d的症状改变情况及不良反应的发生情况.结果 观察组治疗7d后各症状的总有效率分别为91.18％ 、91.18％和85.19％,均优于对照组的72.7％、75.76％、85.19％(均P＜0.05).结论 奥洛他定用于治疗过敏性结膜炎起效快、作用时间长、安全性高,值得临床推广使用.     

Effects of a new formulation of olopatadine ophthalmic solution on nasal symptoms relative to placebo in two studies involving subjects with allergic conjunctivitis or rhinoconjunctivitis

BACKGROUND: A new formulation of olopatadine hydrochloride ophthalmic solution (olopatadine 0.2%) was evaluated in two separate, randomized, placebo-controlled, double-masked, hybrid environmental studies intended to determine efficacy and safety in subjects with histories of seasonal allergic conjunctivitis or rhinoconjunctivitis. DESIGN AND METHODS: In these 10- and 12-week trials (conducted April-August 2003 and July-December 2001, respectively), subjects assessed their ocular signs and symptoms. Additionally, subjects in the 10-week trial evaluated the frequency of their nasal symptoms while subjects in the 12-week trial evaluated both the frequency and severity of their nasal symptoms. The two trials had a combined enrollment of 500 subjects (217 males, 283 females) including 44 children aged 10-17 years; the combined population was 81.4% Caucasian, 9.2% Black, 2% Hispanic, and 7.4% other. Daily throughout these studies, either ragweed (fall study) or grass (spring study) pollen counts were obtained from each investigative center. Slope analyses were conducted on the nasal symptom assessments by pollen count. RESULTS: The nasal results from the two clinical trials are presented herein. In the fall study, relative to placebo, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0355) and itchy nose (p = 0.0032), and reduced the severity of pollen effects on sneezing (p = 0.0451), itchy nose (p = 0.0178), and runny nose (p = 0.0327). In the spring study, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0017) and runny nose (p = 0.0031) relative to placebo. In the fall trial, 2 subjects discontinued due to treatment-related adverse events (tachycardia and dry eye), while in the spring study, no subject discontinued due to a treatment-related adverse event. No subject in either study suffered a treatment-related serious adverse event. CONCLUSIONS: For the subjects enrolled in these studies, olopatadine 0.2% appeared to be safe, well-tolerated, and effective in significantly reducing the frequency and/or severity of some effects of pollen on nasal symptoms.     

Circadian IOP-lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%

PURPOSE: The primary objective of this study was to determine the intraocular pressure- (IOP) lowering efficacy over two consecutive 24-h periods of travoprost 0.004% ophthalmic solution (Travatan) compared to latanoprost 0.005% (Xalatan) dosed once daily in patients with primary open-angle glaucoma or ocular hypertension. METHODS: This was a double-masked trial conducted at the Hospital Clínico San Carlos, Madrid, Spain. The primary objective of this study was to determine the IOP lowering efficacy of travoprost and latanoprost. During the eligibility visit, patients' IOP was measured throughout two consecutive 24-h periods every 4 h. Patients were then randomized to travoprost or latanoprost (one drop at 8 p.m. daily for 2 weeks). Sixty-two patients were randomized (travoprost n = 32; latanoprost n = 30). IOP was measured at week 2 every 4 h throughout two 24-h periods. All measurements were taken in both supine and sitting positions with the aid of Perkins applanation tonometry. Limitations of the study include a small sample size (due to the difficulty in recruiting patients in a study of this type) which enrolled only Caucasian patients and a short study duration. However, with 25 subjects per group, there was at least 90% power to detect a mean IOP change from baseline of 2.9 mmHg and 80% power to detect a difference of 2.5 mmHg between treatments. RESULTS: Patients on travoprost therapy showed lower mean IOP levels than those on latanoprost. This difference was statistically significant (p < 0.05) at 12, 16, 20, 24, 36, 40, and 48 h after the last dose for the supine position. The mean IOPs in the supine position throughout the first and the second 24-h period of the week 2 visit as well as for the 48-h visit were statistically lower (p < 0.05) for the travoprost group. Adverse events were mild and included hyperemia and corneal staining. Travoprost and latanoprost were both well tolerated. CONCLUSION: Mean IOP values were significantly lower for patients on travoprost for the majority of time points in the supine position.     

Effects of a new formulation of olopatadine ophthalmic solution on nasal symptoms relative to placebo in two studies involving subjects with allergic conjunctivitis or rhinoconjunctivitis

ABSTRACT

Background: A new formulation of olopatadine hydrochloride ophthalmic solution (olopatadine 0.2%) was evaluated in two separate, randomized, placebo-controlled, double-masked, hybrid environmental studies intended to determine efficacy and safety in subjects with histories of seasonal allergic conjunctivitis or rhinoconjunctivitis.

Design and methods: In these 10- and 12-week trials (conducted April–August 2003 and July–December 2001, respectively), subjects assessed their ocular signs and symptoms. Additionally, subjects in the 10-week trial evaluated the frequency of their nasal symptoms while subjects in the 12-week trial evaluated both the frequency and severity of their nasal symptoms. The two trials had a combined enrollment of 500 subjects (217 males, 283 females) including 44 children aged 10–17 years; the combined population was 81.4% Caucasian, 9.2% Black, 2% Hispanic, and 7.4% other. Daily throughout these studies, either ragweed (fall study) or grass (spring study) pollen counts were obtained from each investigative center. Slope analyses were conducted on the nasal symptom assessments by pollen count.

Results: The nasal results from the two clinical trials are presented herein. In the fall study, relative to placebo, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0355) and itchy nose (p = 0.0032), and reduced the severity of pollen effects on sneezing (p = 0.0451), itchy nose (p = 0.0178), and runny nose (p = 0.0327). In the spring study, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0017) and runny nose (p = 0.0031) relative to placebo. In the fall trial, 2 subjects discontinued due to treatment-related adverse events (tachycardia and dry eye), while in the spring study, no subject discontinued due to a treatment-related adverse event. No subject in either study suffered a treatment-related serious adverse event.

Conclusions: For the subjects enrolled in these studies, olopatadine 0.2% appeared to be safe, well-tolerated, and effective in significantly reducing the frequency and/or severity of some effects of pollen on nasal symptoms.     

汉防己甲素滴眼液在兔眼内的药动学

目的:研究汉防己甲素滴眼液(TET)在兔角膜和房水中的药动学。方法:将TET滴入大耳白兔双眼后,分别于不同时间处死家兔,取其房水和角膜组织用高效液相色谱法(HPLC)测定。采用计算机拟合求得药动学参数。结果:TET在角膜组织及房水中均为一室模型,其中角膜组织中于滴药后0.125h时含量最高为(234.9±21.3)μg.g-1,房水中1.5h时的含量最高为(90.3±8.0)μg.L-1。角膜组织中药物质量浓度半衰期为2.2h,房水中为1.0h。结论:汉防己甲素滴眼后能渗透到角膜组织及房水中,为临床应用提供了依据。     

Circadian IOP-lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%*

ABSTRACT

Purpose: The primary objective of this study was to determine the intraocular pressure- (IOP) lowering efficacy over two consecutive 24-h periods of travoprost 0.004% ophthalmic solution (Travatan^?) compared to latanoprost 0.005% (Xalatan^?) dosed once daily in patients with primary open-angle glaucoma or ocular hypertension.

Methods: This was a double-masked trial conducted at the Hospital Clínico San Carlos, Madrid, Spain. The primary objective of this study was to determine the IOP lowering efficacy of travoprost and latanoprost. During the eligibility visit, patients’ IOP was measured throughout two consecutive 24‐h periods every 4?h. Patients were then randomized to travoprost or latanoprost (one drop at 8 p.m. daily for 2 weeks). Sixty-two patients were randomized (travoprost n = 32; latanoprost n = 30). IOP was measured at week 2 every 4?h throughout two 24‐h periods. All measurements were taken in both supine and sitting positions with the aid of Perkins applanation tonometry. Limitations of the study include a small sample size (due to the difficulty in recruiting patients in a study of this type) which enrolled only Caucasian patients and a short study duration. However, with 25 subjects per group, there was at least 90% power to detect a mean IOP change from baseline of 2.9?mmHg and 80% power to detect a difference of 2.5?mmHg between treatments.

Results: Patients on travoprost therapy showed lower mean IOP levels than those on latanoprost. This difference was statistically significant (?p < 0.05) at 12, 16, 20, 24, 36, 40, and 48?h after the last dose for the supine position. The mean IOPs in the supine position throughout the first and the second 24‐h period of the week 2 visit as well as for the 48‐h visit were statistically lower (?p < 0.05) for the travoprost group. Adverse events were mild and included hyperemia and corneal staining. Travoprost and latanoprost were both well tolerated.

Conclusion: Mean IOP values were significantly lower for patients on travoprost for the majority of time points in the supine position.     

国产与进口乌拉地尔的临床疗效观察

目的 :通过国产乌拉地尔与进口同类药物压宁定对高血压患者的临床疗效观察 ,探讨两者疗效差异的异同性和优良特性。方法 :随机双盲对照临床研究。结果 :SBP、SDP、HR在用药后改善明显 ,停药后观察 2 4h血压仍然维持在较低水平。乌拉地尔 (URA)组总有效率为 97.4 % ,压宁定 (EBR)组总有效率为 95 .2 % ,两组比较无显著性差异 (P >0 .0 5 )。结论 :国产乌拉地尔具有与国外同类产品相同的药效机制和作用疗效 ,临床使用降压效果安全、快速、有效 ,降压温和 ,副作用少。     

他克莫司联合奥洛他定治疗过敏性结膜炎的疗效观察

目的探讨他克莫司滴眼液联合盐酸奥洛他定滴眼液治疗过敏性结膜炎的临床疗效。方法选取2015年1月—2016年12月四川大学华西医院眼科收治的过敏性结膜炎患者120例为研究对象,按随机数字法将所有患者分为对照组和治疗组,每组各60例。对照组给予盐酸奥洛他定滴眼液,1~2滴/次,3次/d。治疗组在对照组基础上给予他克莫司滴眼液,1滴/次,2次/d。两组患者均连续治疗1周。观察两组的临床疗效,比较两组的Schirmer试验、泪膜破裂时间(BUT)、角膜荧光素染色评分和症状体征改善时间。结果治疗后,对照组和治疗组的总有效率分别为81.67%、96.67%,两组比较差异具有统计学意义(P0.05)。治疗后,两组Schirmer试验、BUT明显升高,角膜荧光素染色评分、症状评分明显降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组结膜充血、眼痒、流泪改善时间均明显短于对照组,两组比较差异具有统计学意义(P0.05)。结论他克莫司滴眼液联合盐酸奥洛他定滴眼液治疗过敏性结膜炎具有较好的临床疗效,可改善临床症状,缩短症状体征改善时间,具有一定的临床推广应用价值。