The safety data described below were based on trials that evaluated BREO ELLIPTA 100/25 mcg in 1,757 patients and BREO ELLIPTA 200/25 mcg in 745 patients. While patients aged 12 to 17 years were included in these trials, BREO ELLIPTA 200/25 mcg is not approved for use in this age group [see Dosage and Administration (2.2)].

One additional 24-week trial enrolled 902 pediatric patients with asthma. In this trial, BREO ELLIPTA 100/25 mcg was studied in 117 patients aged 12 to 17 years and BREO ELLIPTA 50/25 mcg was studied in 337 patients aged 5 to 11 years.

Adult Patients

The safety of BREO ELLIPTA for the maintenance treatment of asthma in adult patients was based on the data from Trials 8, 9, 10, 11, and 12 [see Clinical Studies (14.2)]. Trial 8 was a 12-week trial that evaluated the efficacy of BREO ELLIPTA 100/25 mcg in patients with asthma compared with fluticasone furoate 100 mcg and placebo. The incidence of adverse reactions associated with BREO ELLIPTA 100/25 mcg is shown in Table 3.

Trial 9 was a 12-week trial that evaluated the efficacy of BREO ELLIPTA 100/25 mcg, BREO ELLIPTA 200/25 mcg, and fluticasone furoate 100 mcg in patients with asthma. This trial did not have a placebo arm. The incidence of adverse reactions associated with BREO ELLIPTA 100/25 mcg and BREO ELLIPTA 200/25 mcg is shown in Table 4.

24-Week Trial

Trial 10 was a 24-week trial that evaluated the efficacy of BREO ELLIPTA 200/25 mcg once daily, fluticasone furoate 200 mcg once daily, and fluticasone propionate 500 mcg twice daily in patients with asthma. This trial did not have a placebo arm. In addition to the reactions shown in Tables 3 and 4, adverse reactions occurring in ≥2% of patients treated with BREO ELLIPTA 200/25 mcg included viral respiratory tract infection, pharyngitis, pyrexia, and arthralgia.

12-Month Trial

Long-term safety data are based on a 12-month trial that evaluated the safety of BREO ELLIPTA 100/25 mcg once daily (n = 201), BREO ELLIPTA 200/25 mcg once daily (n = 202), and fluticasone propionate 500 mcg twice daily (n = 100) in patients with asthma (Trial 11). In addition to the reactions shown in Tables 3 and 4, adverse reactions occurring in ≥2% of the patients treated with BREO ELLIPTA 100/25 mcg or BREO ELLIPTA 200/25 mcg for 12 months included pyrexia, back pain, extrasystoles, upper abdominal pain, respiratory tract infection, allergic rhinitis, pharyngitis, rhinitis, arthralgia, supraventricular extrasystoles, ventricular extrasystoles, acute sinusitis, and pneumonia.

Adult and Pediatric Patients Aged 12 to 17 Years Exacerbation Trial

Trial 12 included both adult and pediatric patients 12 years of age and older. Although this trial did not support efficacy of BREO ELLIPTA for maintenance treatment of asthma in pediatric patients 12 to 17 years of age, it was used to evaluate safety in both adult and pediatric patients 12 to 17 years of age. Patients received BREO ELLIPTA 100/25 mcg (n = 1,009) or fluticasone furoate 100 mcg (n = 1,010). Patients participating in this trial had a history of 1 or more asthma exacerbations that required treatment with oral/systemic corticosteroids or emergency department visit or in-patient hospitalization for the treatment of asthma in the year prior to trial entry. Asthma-related hospitalizations occurred in 10 patients (1%) treated with BREO ELLIPTA 100/25 mcg compared with 7 patients (0.7%) treated with fluticasone furoate 100 mcg. Among patients aged 12 to 17 years, asthma-related hospitalizations occurred in 4 patients (2.6%) treated with BREO ELLIPTA 100/25 mcg (n = 151) compared with 0 patients treated with fluticasone furoate 100 mcg (n = 130). There were no asthma-related deaths or asthma-related intubations observed in this trial.

Pediatric Patients Aged 5 to 17 Years

The safety of BREO ELLIPTA for the maintenance treatment of asthma in pediatric patients 5 years and older was based on the data from Trial 14, a 24-week clinical trial that enrolled 902 patients with asthma aged 5 to 17 years (aged 5 to 11 years [n = 673]; aged 12 to 17 years [n = 229]). Pediatric patients aged 12 to 17 years were randomized to BREO ELLIPTA 100/25 mcg (n = 117) or fluticasone furoate 100 mcg (n = 112). Pediatric patients aged 5 to 11 years were randomized to BREO ELLIPTA 50/25 mcg (n = 337) or fluticasone furoate 50 mcg (n = 336) [see Clinical Studies (14.2)]. Adverse reactions reported in ≥3% of pediatric patients treated with BREO ELLIPTA is shown in Table 5.