Efficacy of Alcaftadine 0.25% (AGN-229666) for Once-daily Prevention of Cedar-Pollen Allergic Conjunctivitis: A Phase 3 Randomized Study.

Purpose: This study evaluated the efficacy and safety of once-daily Alcaftadine 0.25% (AGN-229666) for prevention of signs and symptoms of Japanese cedar-pollen allergic conjunctivitis.Methods: This was a single-center, placebo-, and comparator-controlled study using the Ora-CAC® model of allergic conjunctivitis. The primary endpoint was ocular itching 16 hours after Alcaftadine 0.25% instillation; efficacy at 16 hours was compared with 0.1% Olopatadine, 4 hours after instillation. Secondary endpoints included conjunctival hyperemia.Results: 263 Japanese subjects were enrolled; 224 completed the trial. Alcaftadine 0.25% was statistically superior to vehicle for relief of ocular itching at 16 hours (p < .0001). Alcaftadine 0.25% at 16 hours was non-inferior to Olopatadine at 4 hours. Alcaftadine 0.25% was significantly better than vehicle for relief of conjunctival hyperemia. All treatments showed a low frequency of ocular adverse events.Conclusion: Once-daily Alcaftadine 0.25% is safe and effective in preventing signs and symptoms of Japanese cedar-pollen allergic conjunctivitis.

Safety and Tolerability of High-Dose Budesonide/Formoterol via Turbuhaler® in Japanese Patients with Asthma : A Randomized, Double-Blind, Crossover, Active Comparator-Controlled, Phase III Study.

BACKGROUND: The use of budesonide/formoterol as both maintenance and reliever therapy in asthma is recommended in many countries; however, there are limited data available for the Asian patient population. OBJECTIVE: This study aimed to evaluate the short-term safety and tolerability of a fixed high-dose combination of the inhaled corticosteroid budesonide and the long-acting ß2-adrenoceptor agonist formoterol with that of the ß2-agonist terbutaline for acute symptom relief in Japanese adults with persistent asthma who were already receiving a combination of budesonide/formoterol maintenance therapy. METHODS: This was a randomized, double-blind, crossover, active comparator-controlled, phase III study. Patients aged 16-65 years with persistent asthma received either budesonide/formoterol 160 mg/4.5 mg ten inhalations daily for 3 days via Turbuhaler® or terbutaline 0.4 mg ten inhalations daily for 3 days via Turbuhaler®, in addition to budesonide/formoterol 160 µg/4.5 mg one inhalation twice daily as maintenance treatment. After a 7- to 14-day washout period, patients crossed over to receive the other medication for a further 3 days. Adverse events (AEs), clinical laboratory variables, 12-lead electrocardiogram (ECG) and vital signs were assessed throughout. RESULTS: Twenty-five patients (mean age 44.3 years, 40% female) were randomized and received at least one dose of study medication. Overall, 14 AEs were reported in 12 out of 25 patients (48%) during high-dose budesonide/ formoterol therapy and 24 AEs were reported in 14 out of 23 patients (61%) during terbutaline therapy. The majority of AEs were mild in intensity and no serious AEs were reported. The most common AEs were tremor (12%) during budesonide/formoterol therapy and tremor (17%), palpitations (13%), tachycardia (13%) and decreased serum potassium (13%) during terbutaline therapy. There were no clinically significant differences from baseline or between groups in laboratory values, vital signs or ECG recordings. CONCLUSION: Budesonide/formoterol 160 µg/4.5 mg ten inhalations daily for 3 days in addition to ongoing budesonide/formoterol 160 µg/4.5 µg one inhalation twice daily maintenance therapy was well tolerated in Japanese adults with persistent asthma.

Safety and tolerability of high-dose budesonide/formoterol via Turbuhaler® in Japanese patients with asthma: a randomized, double-blind, crossover, active comparator-controlled, phase III study.

BACKGROUND: The use of budesonide/formoterol as both maintenance and reliever therapy in asthma is recommended in many countries; however, there are limited data available for the Asian patient population. OBJECTIVE: This study aimed to evaluate the short-term safety and tolerability of a fixed high-dose combination of the inhaled corticosteroid budesonide and the long-acting ß(2)-adrenoceptor agonist formoterol with that of the ß(2)-agonist terbutaline for acute symptom relief in Japanese adults with persistent asthma who were already receiving a combination of budesonide/formoterol maintenance therapy. METHODS: This was a randomized, double-blind, crossover, active comparator-controlled, phase III study. Patients aged 16-65 years with persistent asthma received either budesonide/formoterol 160 µg/4.5 µg ten inhalations daily for 3 days via Turbuhaler® or terbutaline 0.4 mg ten inhalations daily for 3 days via Turbuhaler®, in addition to budesonide/formoterol 160 µg/4.5 µg one inhalation twice daily as maintenance treatment. After a 7- to 14-day washout period, patients crossed over to receive the other medication for a further 3 days. Adverse events (AEs), clinical laboratory variables, 12-lead electrocardiogram (ECG) and vital signs were assessed throughout. RESULTS: Twenty-five patients (mean age 44.3 years, 40% female) were randomized and received at least one dose of study medication. Overall, 14 AEs were reported in 12 out of 25 patients (48%) during high-dose budesonide/formoterol therapy and 24 AEs were reported in 14 out of 23 patients (61%) during terbutaline therapy. The majority of AEs were mild in intensity and no serious AEs were reported. The most common AEs were tremor (12%) during budesonide/formoterol therapy and tremor (17%), palpitations (13%), tachycardia (13%) and decreased serum potassium (13%) during terbutaline therapy. There were no clinically significant differences from baseline or between groups in laboratory values, vital signs or ECG recordings. conclusion: Budesonide/formoterol 160 µg/4.5 µg ten inhalations daily for 3 days in addition to ongoing budesonide/formoterol 160 µg/4.5 µg one inhalation twice daily maintenance therapy was well tolerated in Japanese adults with persistent asthma. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00837967; AstraZeneca study code: D589LC00003.