Conjunctival Allergen Challenge Test Research Articles

Evaluating the efficacy of epinastine ophthalmic solution using a conjunctivitis allergen challenge model in patients with birch pollen allergic conjunctivitis

BackgroundThe efficacy of epinastine 0.05% ophthalmic solution for pollen allergic conjunctivitis has already been shown in a conjunctival allergen challenge (CAC) test using cedar pollen as a challenge. The present study investigated the efficacy of this solution against birch pollen conjunctivitis in a CAC test. MethodsTen adult subjects (eight males and two females) with asymptomatic birch pollen conjunctivitis were enrolled in this study. The average age of the subjects was 41.1 years. This study was conducted during a period without birch pollen dispersion. In each subject, the epinastine 0.05% ophthalmic solution was instilled in one eye, and an artificial tear fluid was instilled in the fellow eye in a double-blind manner. Five minutes or 4 h after the drug instillation, both eyes were challenged with an optimal concentration of birch pollen, and ocular itching and conjunctival hyperemia were then graded. Tears were collected before the drug instillation and 20 min after the pollen challenge, and the histamine level was measured. ResultsThe ocular itching scores and palpebral conjunctival hyperemia scores of the epinastine-treated eyes were significantly lower than those of the contralateral control eyes when the eyes were pretreated with the drug 4 h before the CAC. There was a significant correlation between the tear histamine level and mean ocular itching score of three time points (3, 5 and 10 min) following the CAC in the control eyes but not the epinastine-treated eyes. ConclusionsEpinastine is effective in suppressing ocular itching and conjunctival hyperemia in birch pollen conjunctivitis.

Efficacy of olopatadine versus epinastine for treating allergic conjunctivitis caused by Japanese cedar pollen: a double-blind randomized controlled trial.

IntroductionThe objective of this study was to compare the efficacy and safety of olopatadine versus epinastine in healthy Japanese adults with a history of allergic conjunctivitis to Japanese cedar pollen.MethodsThis Phase IV double-blind randomized controlled clinical trial comprised three clinical visits over 30 days. Screening tests were performed to identify subjects with a history of allergic conjunctivitis to Japanese cedar pollen in terms of skin sensitivity and positive bilateral reactions to a conjunctival allergen challenge (CAC) with Japanese cedar pollen at Visit 1, and confirmation by a positive bilateral CAC reaction at Visit 2. At Visit 3, the subjects were randomized to receive one drop of olopatadine HCl ophthalmic solution 0.1% (olopatadine) in the left or right eye (1:1 ratio). All subjects received one drop of epinastine HCl ophthalmic solution 0.05% (epinastine) in the contralateral eye as an active control. Five min later, the subjects underwent bilateral CAC tests with one drop of the allergen solution at the concentration that elicited positive reactions at Visits 1 and 2. Efficacy outcomes included the severity of ocular itching at 5, 7, and 15 min and the severity of conjunctival hyperemia at 7, 15, and 20 min after the CAC test, as graded by the investigator by biomicroscopy.ResultsFifty people participated in this study (25 per group). Olopatadine significantly reduced ocular itching at 7 and 15 min (both p < 0.05) and conjunctival hyperemia at 7 and 20 min (p = 0.0010 and p < 0.05, respectively) after allergen exposure compared with epinastine. There were no adverse events for either treatment.ConclusionThe results of this single-dose study suggest that olopatadine is superior to epinastine in terms of suppressing ocular itching and hyperemia induced by Japanese cedar pollen during CAC tests. Further studies are needed to confirm these findings in real-life settings.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0156-2) contains supplementary material, which is available to authorized users.

Efficacy of epinastine hydrochloride ophthalmic solution in allergic conjunctivitis by conjunctival cedar pollen allergen challenge

BackgroundEpinastine hydrochloride is a selective histamine H1 receptor antagonist that also inhibits IgE receptor-mediated histamine release from mast cells. ObjectiveTo show the superiority of epinastine 0.05% ophthalmic solution (epinastine) to placebo ophthalmic solution (placebo) and noninferiority to olopatadine 0.1% ophthalmic solution (olopatadine) for cedar pollen antigen-induced ocular itching and conjunctival hyperemia. MethodsThe study was conducted in ophthalmologically asymptomatic adult volunteers with seasonal allergic conjunctivitis using a conjunctival allergen challenge test. Subjects were randomized into 3 groups (n = 87) to evaluate superiority to placebo (visits 4 to 6) and 2 groups (n = 86) to evaluate noninferiority to olopatadine (visit 7). At each visit, a single administration of the study medication was instilled at 15 minutes (visit 4), 4 hours (visit 5), 8 hours (visit 6), and 4 hours (visit 7) before the conjunctival allergen challenge test. Ocular itching and conjunctival hyperemia of allergic conjunctivitis were assessed after the conjunctival allergen challenge test. ResultsFor the primary end point, epinastine showed superiority to placebo for the inhibition of ocular itching and conjunctival hyperemia induced at 4 hours after the dose (equivalent to 4-times-daily dosing). For the secondary end points, epinastine significantly inhibited itching and conjunctival hyperemia induced at 15 minutes and 8 hours after the dose (equivalent to 2-times-daily dosing) compared with placebo. In addition, epinastine demonstrated noninferiority to olopatadine for ocular itching and conjunctival hyperemia. No adverse drug reactions or serious adverse events were reported throughout the study, indicating that epinastine has a good safety profile. ConclusionEpinastine is effective and safe for the treatment of allergic conjunctivitis. Trial RegistrationClinicaltrials.gov identifier NCT01363700.

Treatment of allergic conjunctivitis with bepotastine besilate ophthalmic solution 1.5%.

PurposeTo examine the pooled per-protocol ocular end points from two conjunctival allergen challenge (CAC) clinical trials of the dual-action antihistamine bepotastine besilate ophthalmic solution (BBOS) 1.5%.MethodsTwo Phase III, placebo-controlled, double-masked, randomized clinical trials were conducted at a total of six separate centers using the CAC model of allergic conjunctivitis. The same study design was employed for both clinical trials, with subjects randomly assigned to either BBOS 1.5% (n=78) or placebo (n=79) treatment. Each subject received one eye drop of the test agent bilaterally at different study visits 15 minutes, 8 hours, or 16 hours prior to a CAC. Primary ocular end points included changes in ocular itching reported at 3, 5, and 7 minutes and conjunctival hyperemia assessed at 7, 15, and 20 minutes following each CAC. Secondary ocular end points included chemosis as well as episcleral and ciliary hyperemia judged by investigators, and tearing (scored as either absent or present) and eyelid swelling judged by subjects.ResultsA statistically significant reduction in ocular itching was observed for BBOS 1.5% treatment compared to placebo at all time points (P<0.0001), while measures for onset and 8-hour persistence of action also reached clinical significance (ie, ≥1.0 unit difference) at a majority of time points. In addition, a significant reduction in conjunctival hyperemia was achieved at a majority of time points during the onset of action CAC test. Secondary end points were also significantly improved compared to placebo, most prominently for reduced tearing at all study visits and reduced eyelid swelling at the onset of action and 8-hour study visits. Adverse events were generally mild and transient.ConclusionBBOS 1.5% rapidly reduced CAC-induced ocular itching with duration of effectiveness of at least 8 hours after dosing. Certain secondary signs of inflammation were also significantly reduced.

Prolonged Effectiveness of Bepotastine Besilate Ophthalmic Solution for the Treatment of Ocular Symptoms of Allergic Conjunctivitis

This clinical trial evaluated the safety and effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo for the treatment of ocular itching and conjunctival hyperemia (redness) using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis when dosed 16 h before a CAC test. Subjects with a history of allergic conjunctivitis were assigned to receive placebo or bepotastine besilate ophthalmic solution 1.0% or 1.5% in a single-center, randomized, placebo-controlled clinical trial. Eligible subjects (n=107) aged 10 years and older with a history of allergic conjunctivitis who had a reproducible positive reaction to a CAC were enrolled and dosed with test agent. The primary trial objectives included assessment of ocular itching and conjunctival redness at 16 h after instillation of test agent. Reductions in several CAC-induced secondary symptoms and signs of allergic conjunctivitis were also evaluated for tearing, ciliary and episcleral redness, eyelid swelling, chemosis, and mucous discharge. Bepotastine besilate ophthalmic solution 1.5% demonstrated clinical effectiveness and statistical significance in comparison to placebo for the reduction in CAC-induced ocular itching 16 h after drug administration. Bepotastine besilate ophthalmic solution 1.0% also achieved statistical significance in comparison to placebo for reducing ocular itching at all time points 16 h after dosing. Statistically significant reduction (P≤0.05) was additionally seen in this CAC test for the secondary ocular efficacy variable of allergen-induced tearing for bepotastine besilate ophthalmic solution 1.5%. No clinical benefit was seen for reducing the coprimary efficacy variable of conjunctival redness with the CAC model of allergic conjunctivitis. Bepotastine besilate ophthalmic solution 1.5% produced predefined clinically meaningful reduction in CAC-induced ocular itching and tearing in a single-site trial and was more effective than bepotastine besilate ophthalmic solution 1.0% and placebo for reducing ocular itching in a CAC test 16 h after dosing.

Bepotastine besilate ophthalmic solution for the relief of nonocular symptoms provoked by conjunctival allergen challenge

Bepotastine besilate is a selective histamine1-receptor antagonist and mast cell stabilizer with inhibitory effects on eosinophilic activity. To evaluate the safety and efficacy of 1.5% bepotastine besilate ophthalmic solution in alleviating nonocular symptoms induced by a conjunctival allergen challenge (CAC), a clinical model of allergic conjunctivitis. This was a single-center, double-masked, randomized, placebo-controlled clinical trial performed from March 1 to April 4, 2007. Patients 10 years or older with a history of allergic conjunctivitis and a reproducible, positive, clinical response to a CAC were eligible. Patients received either placebo or 1.5% bepotastine besilate, 1 drop in each eye. After 15 minutes, 8 hours, or 16 hours after dosing, a CAC was performed and patients evaluated nonocular symptoms using standardized grading scales. Seventy-one patients were enrolled in the study, and 66 comprised the per protocol population. A clinically meaningful reduction (> or = 1.0 unit) compared to placebo was achieved for rhinorrhea and nasal congestion at most time points after 1.5% bepotastine besilate instillation at 8 hours before a CAC test. Significant reductions (P < or = .05) in mean values were seen with 1.5% bepotastine besilate at 15 minutes and 8 hours after dosing for CAC-induced nasal congestion, rhinorrhea, ear or palate pruritus, nasal pruritus, and summed nonocular composite symptom (NOCS) scores and also at 16 hours after dosing for nasal congestion and rhinorrhea. The 1.5% bepotastine besilate formulation produced statistically significant reductions after a CAC in individual nonocular symptoms and NOCS scores at onset of allergic response and for at least 8 hours after instillation, with the greatest reduction seen for nasal congestion and rhinorrhea.

Multicenter Clinical Evaluation of Bepotastine Besilate Ophthalmic Solutions 1.0% and 1.5% to Treat Allergic Conjunctivitis

To evaluate the effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo at reducing ocular itching and conjunctival hyperemia in the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Prospective, double-masked, randomized, placebo-controlled, phase 3 CAC clinical trial. This multicenter trial enrolled 130 subjects with a clinical history of allergic conjunctivitis who were randomized to bepotastine besilate ophthalmic solution 1.0%, 1.5%, or 0.0% (placebo). One drop of test agent was instilled bilaterally before a CAC test evaluating responses at 15 minutes, 8 hours, or 16 hours after test agent instillation. Primary efficacy outcomes were unit improvements relative to placebo in mean scores for ocular itching and conjunctival hyperemia, each graded on 0- to 4-unit scales. Reductions of 1.2 units or more in mean ocular itching scores at all time points for both bepotastine besilate ophthalmic solutions 1.0% and 1.5% were observed at onset of action and 8-hour duration-of-action CAC tests (P < .0001). Statistically significant reductions in conjunctival hyperemia (P < or = .0125) were observed for bepotastine besilate ophthalmic formulations only at the onset of action CAC test. Bepotastine besilate ophthalmic solutions 1.0% and 1.5% both substantially decreased CAC-induced ocular itching for at least 8 hours after dosing. Reductions in conjunctival hyperemia after a CAC, although statistically significant for bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo when assessed at 15 minutes after dosing, were modest.

Time to onset and duration of action of the antihistamine bepotastine besilate ophthalmic solutions 1.0% and 1.5% in allergic conjunctivitis: A phase III, single-center, prospective, randomized, double-masked, placebo-controlled, conjunctival allergen challenge assessment in adults and children

Background: Bepotastine besilate is a highly selective histamine H 1-receptor antagonist with antihistaminic, mast cell stabilizing, and anti-inflammatory activity. Based on a history of clinical effectiveness and tolerability of oral bepotastine besilate in the treatment of allergic symptoms, bepotastine besilate is being tested as a potential ophthalmic medication for allergic conjunctivitis. Objective: The aim of this study was to assess the effects of bepotastine besilate ophthalmic solution 1.0% and 1.5% for the treatment of ocular itching and conjunctival hyperemia in a conjunctival allergen challenge (CAC) model in adults and children. Methods: This Phase III, single-center, prospective, randomized, double-masked, placebo-controlled, CAC clinical trial enrolled patients ≥10 years of age with a history of allergic conjunctivitis, skin-test reaction, and CAC response. Patients received bepotastine besilate ophthalmic solution 1.0%, bepotastine besilate ophthalmic solution 1.5%, or placebo, 1 drop on each eye on days 14 ± 3 and 28 ± 3. The primary efficacy end points, patient-assessed ocular itching (at 3, 5, and 7 minutes) and investigator-assessed conjunctival hyperemia (at 7, 15, and 20 minutes), were determined after CAC according to standardized 5-point scales (0 = none to 4 = severe). Clinical significance was defined in the protocol as ≥1.0-U between-group difference in mean ocular itching scores at the majority of time points at a study visit and also a ≥0.5-U difference at all time points. Tolerability of the test agent was assessed by visual acuity, slit-lamp biomicroscopy, intraocular pressure, dilated funduscopy, and adverse events. Results: A total of 107 patients (male, 54%; age range, 11–73 years; white race/ethnicity, 93%) received investigational product and comprised the intent-to-treat (ITT) population (bepotastine besilate ophthalmic solution 1.0%, 36 patients; bepotastine besilate ophthalmic solution 1.5%, 35; and placebo, 36). All 107 patients received investigational product at visit 3A (day 0) and were included in the ITT population. Of the 107 patients who were enrolled, 103 completed the study without a protocol deviation or violation. The 1.0% and 1.5% solutions were associated with clinically and statistically significant reductions in mean ocular itching scores compared with placebo on the 15-minute onset-of-action and 8-hour duration-of-action CAC tests (reductions, 1.3–1.5 U and 1.0–1.7 U respectively; all, P < 0.001). Statistically significant reductions in conjunctival hyperemia were achieved with both bepotastine besilate concentrations. Overall, 13 patients experienced a treatmentemergent adverse event considered related to the study drug (bepotastine besilate ophthalmic solution 1.0%, 6 patients; bepotastine besilate ophthalmic solution 1.5%, 4; and placebo, 3). Conclusions: In this CAC model of allergic conjunctivitis in adults and children, bepotastine besilate ophthalmic solutions 1.0% and 1.5% were associated with clinically and statistically significant reductions in ocular itching, but not conjunctival hyperemia, within 15 minutes that were maintained for at least 8 hours after administration. Both solutions were well tolerated. ClinicalTrials.gov identifier: NCT00424398.

Do skin prick and conjunctival provocation tests predict symptom severity in seasonal allergic rhinoconjunctivitis?

In the investigation of seasonal allergic rhinoconjunctivitis (SAR), quantitative skin and conjunctival allergen challenge tests are used to measure individual allergen sensitivity. These tests are reproducible and relate well to prevalence but their relationship to symptom severity is less well established. We wished to determine if quantitative skin prick tests (QSPT) and conjunctival provocation tests (CPTs) using a single grass pollen allergen extract are reproducible and predict symptom severity in SAR. We retrospectively analysed data from 91 participants in a previously published randomized placebo controlled study of low dosage allergen immunotherapy who were randomized to receive placebo treatment. We examined the relationship between pre-seasonal QSPT, CPT and SAR symptoms. We found a high level of reproducibility when repeated measures were compared for both the QSPT (P < 0.001) and the CPT (P < 0.001) and moderate correlation (0.49) between the standard skin prick test (SPT) and the QSPT (P < 0.001). We found weak negative correlation (-0.27) between the QSPT and the CPT (P < 0.001). We found no correlation between seasonal symptom, use of rescue medication or quality of life (QOL) scores and pre-seasonal QSPT or CPT. Conclusion In the assessment of seasonal rhinoconjunctivitis, quantitative skin and conjunctival allergen challenge tests are strongly reproducible, although there is no correlation between these tests and seasonal symptom, use of rescue medication or QOL scores.

Efficacy of Levocabastine Hydrochloride Ophthalmic Suspension in the Conjunctival Allergen Challenge Test in Japanese Subjects with Seasonal Allergic Conjunctivitis

This study was conducted to investigate the efficacy and safety of 0.025% levocabastine hydrochloride in Japanese subjects with seasonal allergic conjunctivitis and its duration of action using the conjunctival allergen challenge (CAC) test. Twenty-four asymptomatic subjects were randomized to instill 0.025% levocabastine ophthalmic suspension in one eye and vehicle in the other eye 10 minutes before the CAC test. Signs and symptoms of allergic conjunctivitis were scored 10, 15, and 25 minutes after the CAC test. The duration of drug effects was also evaluated by allergen rechallenge 4 hours after levocabastine administration. The itching score for each eye as the primary efficacy endpoint was assessed 15 minutes after the CAC test using a 5-point scale. The mean itching score in the levocabastine-treated group was 0.08 +/- 0.06, which was significantly lower than the mean score of 1.98 +/- 0.16 in the vehicle group (P < 0.0001). The redness and chemosis of the conjunctiva were also improved significantly compared with the vehicle group. Levocabastine showed prolonged efficacy in inhibiting itching (0.42 +/- 0.12 vs 0.94 +/- 0.17, P < 0.0002) and redness (1.04 +/- 0.18 vs 1.42 +/- 0.22, P < 0.01) of the conjunctiva upon the rechallenge test. No significant topical or systemic adverse safety findings were observed in the levocabastine group. The results indicate that 0.025% levocabastine ophthalmic suspension is effective and safe in the treatment of allergic conjunctivitis with a duration of action of at least 4 h.

A randomized, double-blind, parallel-group comparison of olopatadine 0.1% ophthalmic solution versus placebo for controlling the signs and symptoms of seasonal allergic conjuctivitis and rhinoconjunctivitis

Background: The most common form of allergic ocular disease is seasonal allergic conjunctivities, coinciding with the pollen season and generally associated with rhinitis. Symptoms of allergic conjunctivitis include ocular itching, hyperemia, tearing, mucus production, foreign body sensation, chemosis, and lid edema. Similarly, the primary symptoms of allergic rhinoconjunctivitis are nasal itching, irritation, sneezing, watery rhinorrhea, and congestion combined with ocular itching, tearing, and swelling. Objective: This study compared olopatadine 0.1% ophthalmic solution with placebo eyedrops (over-the-counter artificial tear product), instilled in the eye, with regard to the prevention and relief of the ocular and nasal symptoms of seasonal allergic conjunctivitis and rhinoconjunctivitis. Methods: This was a randomized, double-blind, parallel-group study, conducted at 7 US centers, to instill either olopatadine 0.1% ophthalmic solution or placebo eyedrops (artificial tears) in both eyes twice daily for 10 weeks. Patients were evaluated for efficacy (intent-to-treat) and safety. Only patients with proven grass pollen allergy (dermal and conjunctival allergen challenge tests) were selected; all patients were studied during the same period, historically shown to be grass season; and grass pollen counts were obtained. Results: A total of 131 patients (64 olopatadine; 67 placebo) were assessed for efficacy (intent-to-treat); 132 patients were assessed for safety. The mean (SD) age of participants was 38.53 (11.61) years (range, 18 to 87 years), and 58.0% were women ( 76 131 ), with no significant differences between groups for age or sex. In the olopatadine group, 1.6% of patients were black ( 1 64 ), compared with 14.9% of the placebo group ( 10 67 ) ( P = 0.005). Mean scores of ocular itching and hyperemia were lower at all assessment times with olopatadine than placebo. The difference was statistically significant ( P < 0.05) for itching on days 7, 14, 35, 63, and 70, and for hyperemia on days 14, 28, 42, and 63, after correction for multiplicity. Linear regression slopes predicting ocular itching and hyperemia from the pollen count were significantly lower ( P < 0.003 and P < 0.035, respectively) with olopatadine than with placebo. Similar results were obtained for rhinorrhea, sneezing, and nasal itching ( P < 0.006, P < 0.012, and P < 0.034, respectively). With placebo, the proportion of patients with frequent ocular itching and hyperemia increased as a function of pollen level; however, with olopatadine, the proportions remained low and virtually constant. Conclusion: In the population studied, olopatadine 0.1% ophthalmic solution controlled ocular and nasal symptoms of allergic conjunctivitis and rhinoconjunctivitis and was well tolerated when administered twice daily for 10 weeks.