Efficacy, Safety, and Systemic Exposure of Once-Daily Indacaterol Acetate in Pediatric Asthma: A Randomized, Double-Blind, Controlled Dose-Finding Study.

BACKGROUND: Indacaterol acetate (IND), a long-acting ß2-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od) treatment for asthma in children. This study examined the efficacy, safety, and systemic exposure of IND 75 µg and IND 150 µg in children with persistent asthma. METHODS: In this Phase IIb, multicenter, randomized, double-blind, parallel-group study, pediatric patients (aged ≥ 6 to < 12 years) with persistent asthma were randomized (1:1) to receive either IND 75 µg od or IND 150 µg od via Breezhaler® in combination with ICS background therapy. The primary endpoint was change from baseline in pre-dose trough forced expiratory volume in one second (FEV1) after two weeks of treatment. RESULTS: In total, 80 patients received IND 75 µg (n = 39) or IND 150 µg (n = 41). The study met its primary endpoint; both doses demonstrated improvements in pre-dose trough FEV1 from baseline to Day 14 (mean change [Δ]: 212 mL, IND 75 µg; 171 mL, IND 150 µg). The secondary spirometry parameters (post-dose FEV1 after 1-h, post-dose forced vital capacity; morning and evening peak expiratory flow) also improved. Overall, 36.1% in IND 75 µg group and 25% patients in IND 150 µg group achieved a decrease from baseline in Pediatric Interviewer-administered Asthma Control Questionnaire score of ≥ 0.5 units. A dose-dependent increase in plasma IND concentration was noted between the two groups. Both IND doses demonstrated an acceptable safety profile. CONCLUSIONS: Once-daily IND 75 µg and IND 150 µg via Breezhaler® in combination with background ICS therapy provided substantial bronchodilation in children with asthma and were well tolerated. Taken together, these clinical and systemic exposure findings support IND 75 µg as the most appropriate dose for evaluation in Phase III trials in combination with MF in pediatric asthma. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02892019; 08-Sep-2016).

Determinants of COVID-19 vaccine acceptance in a high infection-rate country: a cross-sectional study in Russia.

BACKGROUND: COVID-19 vaccine development is proceeding at an unprecedented pace. Once COVID-19 vaccines become widely available, it will be necessary to maximize public vaccine acceptance and coverage. OBJECTIVE: This research aimed to analyze the predictors of COVID-19 vaccine acceptance in Russia. METHODS: A cross-sectional online survey was conducted among Russian adults from September 26th to November 9th, 2020. Predictors of the intent to take up COVID-19 vaccination were explored using logistic regression. RESULTS: Out of 876 participants, 365 (41.7%) would be willing to receive the vaccine if it became available. Acceptance increased for a vaccine with verified safety and effectiveness (63.2%). Intention to receive the COVID-19 vaccine was relatively higher among males (aOR=2.37, 95% CI 1.41-4.00), people with lower monthly income (aOR=2.94, 95%CI 1.32-6.57), and with positive trust in the healthcare system (aOR=2.73, 95% CI 1.76-4.24). The Russian people were more likely to accept the COVID-19 vaccine if they believed that the vaccine reduces the risk of virus infection (aOR=8.80, 95%CI 5.21-14.87) or relieves the complications of the disease (aOR=10.46, 95%CI 6.09-17.96). Other barriers such as being unconcerned about side-effects (aOR=1.65, 95%CI 1.03-2.65) and the effectiveness and safety of the vaccination (aOR=2.55, 95%CI 1.60-4.08), also affected acceptance. CONCLUSIONS: The study showed the usefulness of the health belief model constructs in understanding the COVID-19 vaccination acceptance rate in the Russian population. This rate was influenced by sociodemographic and health-related characteristics, and health beliefs. These findings might help guide future efforts for policymakers and stakeholders to improve vaccination rates by enhancing trust in the healthcare system.