The efficacy and safety of fluticasone/salmeterol compared to fluticasone in children younger than four years of age.

BACKGROUND: Fluticasone propionate 50 µg/salmeterol xinafoate 25 µg (FP/SAL) is widely used in adults and children with asthma, but there is sparse information on its use in very young children. METHODS: This was a randomized, double-blind, multicentre, controlled trial conducted in children aged 8 months to 4 years. During a 2-week run-in period, they all received FP twice daily. At randomization, they commenced FP/SAL or FP twice daily for 8 weeks. All were then given FP/SAL only, in a 16-week open-label study continuation. Medications were inhaled through an AeroChamber Plus with attached face mask. The primary end-point was mean change in total asthma symptom scores from baseline to the last 7 days of the double-blind period. Analyses were undertaken in all children randomized to treatment and who received at least one dose of study medication. RESULTS: Three hundred children were randomized 1:1 to receive FP/SAL or FP. Mean change from baseline in total asthma symptom scores was -3.97 for FP/SAL and -3.01 with FP. The between-group difference was not statistically significant (P = 0.21; 95% confidence interval: -2.47, 0.54). No new safety signals were seen with FP/SAL. CONCLUSION: This is the first randomized, double-blind study of this size to evaluate FP/SAL in very young children with asthma. FP/SAL did not show superior efficacy to FP; no clear add-on effect of SAL was demonstrated. No clinically significant differences in safety were noted with FP/SAL usage.

Health Status Progression Measured Using Weekly Telemonitoring of COPD Assessment Test Scores Over 1 Year and Its Association With COPD Exacerbations.

Background: A previous longitudinal study of chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) score changes suggested patients fall into 3 patterns: stable, improving, and worsening. This study assessed the evolution of CAT scores over time and its relationship to exacerbations. Methods: In total, 84 participants used a telemedicine platform to complete CAT weekly for 52 weeks. Completion rates, annualized change in CAT scores, and learning effects were measured, as well as CAT changes of >4 units during look-back periods of 4 and 8 weeks. In a subgroup of participants with at least a 25% completion rate (adherent group, n=68 [81%]), the relationship between change in CAT score and exacerbations at any time during the study was examined post hoc. Results: Linear regression showed that 50%, 22%, and 28% of the adherent subgroup had CAT scores indicating worsening, stable, and improving health status, respectively. In the adherent subgroup, 70% (n=7/10) of participants who had an exacerbation during the study had worsening CAT scores, versus 47% (n=27/58) without an exacerbation. The hazard ratio association between CAT score increase and moderate exacerbation was 1.13 (95% confidence interval: 1.03-1.24). Most participants experienced at least one CAT score change of >4 units, and 7% showed an initial learning effect with a median of 2 weeks. Conclusion: Measuring trends in CAT scores may allow future studies to group patients into 3 defined categories of change over time and quantify CAT change trajectories to assess treatment response and potentially predict medium-term outcomes within individual patients.

A Telemedicine Approach for Monitoring COPD: A Prospective Feasibility and Acceptability Cohort Study.

Background: Telemedicine may help the detection of symptom worsening in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in improved outcomes. This study aimed to determine the feasibility and acceptability of telemedicine among patients with COPD and physicians and facility staff in Japan. Methods: This was a 52-week multicenter, prospective, single-arm, feasibility and acceptability cohort study of Japanese patients ≥40 years of age with COPD or asthma-COPD overlap. Participants underwent training to use YaDoc, a telemedicine smartphone App, which included seven daily symptom questions and weekly COPD Assessment Test (CAT) questions. The primary endpoint was participant compliance for required question completion. The secondary endpoint was participant and physician/facility staff acceptability of YaDoc based on questionnaires completed at Week 52. The impact of the Japanese COVID-19 pandemic state of emergency on results was also assessed. Results: Of the 84 participants enrolled (mean age: 68.7 years, 88% male), 72 participants completed the study. Completion was high in the first six months but fell after that. Median (interquartile range [IQR]) compliance for daily questionnaire entry was 66.6% (31.0-91.8) and 81.0% (45.3-94.3) for weekly CAT entry. Positive participant responses to the exit questionnaire were highest regarding YaDoc ease of use (83.8%), positive impact on managing health (58.8%), and overall satisfaction (53.8%). Of the 26 physicians and facility staff enrolled, 24 completed the study. Of these, the majority (66.7%) responded positively regarding app facilitation of communication between physicians and participants to manage disease. Compliance was similar before and after the first COVID-19 state of emergency in Japan. Conclusion: Daily telemedicine monitoring is potentially feasible and acceptable to both patients and physicians in the management of COPD. These results may inform potential use of telemedicine in clinical practice and design of future studies. Clinical Trial Registration: JapicCTI-194916.

Long-term (52 weeks) safety and tolerability of umeclidinium in Japanese patients with chronic obstructive pulmonary disease.

Objective Umeclidinium bromide (UMEC) 62.5 µg is a long-acting muscarinic antagonist (LAMA) that is administered once daily via inhalation for chronic obstructive pulmonary disease (COPD) treatment. The objective of this study was to evaluate the safety and tolerability of long-term treatment with UMEC 125 µg in Japanese patients with COPD. Methods This was a 52 week, multicenter, open-label study to evaluate the safety and tolerability of UMEC 125 µg once daily delivered via a novel dry powder inhaler (nDPI) in Japanese patients with COPD. The primary endpoint was the incidence and severity of all adverse events (AEs) throughout the 52 week treatment period. Clinical trial registration number ClinicalTrials.gov identifier is NCT01702363. Results A total of 153 patients were enrolled in the study. Of these, 131 patients started treatment with UMEC 125 µg, and 111 patients (85%) completed the study. AEs did not differ greatly in incidence over the various time periods (Weeks 0 to 12, 13 to 24, 25 to 36, and 37 to 52 of treatment) and did not increase with continued treatment. The incidence of drug-related AEs associated with the pharmacological effects of LAMAs (including constipation, blurred vision, and thirst) was low. Serious adverse events (SAEs) during the treatment period were reported in 17 patients (13%). SAEs reported in more than one patient were COPD exacerbation and pneumonia (3 patients each, 2%). One SAE of angina pectoris was considered to be drug related. No fatalities were reported during this study. Conclusions No new AEs were identified beyond those attributable to the pharmacological effects of LAMAs. UMEC 125 µg was well tolerated over 52 weeks of treatment in Japanese patients with COPD.

Evaluation of safety and efficacy of intravenous zanamivir in the treatment of hospitalized Japanese patients with influenza: an open-label, single-arm study.

BACKGROUND: Zanamivir is a neuraminidase (NA) inhibitor used for the treatment of influenza. There is an unmet need for a parenteral influenza antiviral therapy to treat hospitalized patients. Therefore the safety and efficacy profile of intravenous zanamivir (IVZ) was examined in Japanese patients with severe influenza. METHODS: The primary objective of this study was to evaluate the safety of IVZ in Japanese patients. Clinical outcome and virological data were also assessed as secondary measures. Patients hospitalized with influenza were treated with IVZ 600 mg twice daily for five days. RESULTS: A total of 21 subjects received IVZ; 17 subjects (81%) were infected with influenza A/H3N2 and 3 (14%) were infected with influenza B. One subject was not laboratory confirmed influenza-positive. Thirteen subjects received the first dose of IVZ within two days of the onset of influenza symptoms and six subjects had been treated with prior influenza antiviral therapy. Overall adverse events (AEs) and serious adverse events (SAEs) were reported in 13 (62%) and 4 (19%) subjects, respectively. There were no patterns of AEs or SAEs. Median time to clinical response and time to virological improvement were approximately 4 days (range 0.5-22) and 3 days (range 2-5), respectively. CONCLUSIONS: In this study there were no new significant safety findings or patterns of AEs related to IVZ and therefore the safety profile was confirmed for a small sample of Japanese hospitalized patients with influenza. In addition, improvements in clinical and virological measures suggestive of the clinical usefulness were also observed. ClinicalTrials.gov NCT01527110; GSK NAI115215.