6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult and Pediatric Subjects Aged 12 Years and Older The safety of ARNUITY ELLIPTA was evaluated in 10 double-blind, parallel-group, controlled trials (7 with placebo) of 8 to 76 weeks’ duration that enrolled 6,219 subjects with asthma.
Doses of fluticasone furoate studied ranged from 25 to 800 mcg. ARNUITY ELLIPTA 100 mcg was studied in 1,663 subjects, and ARNUITY ELLIPTA 200 mcg was studied in 608 subjects. Subject ages ranged from 12 to 84 years, 65% were female, and 75% were Caucasian. In these trials, the proportion of subjects who discontinued study treatment early due to adverse reactions was 2% for subjects treated with both ARNUITY ELLIPTA 100 mcg and ARNUITY ELLIPTA 200 mcg and ≤1% for placebo-treated subjects.
Serious adverse events, whether considered drug-related or not by the investigators, that occurred in more than 1 subject and in a greater percentage of subjects treated with ARNUITY ELLIPTA than placebo included hypertension, abscess, breast cancer, traumatic limb amputation, subarachnoid hemorrhage, and intervertebral disc protrusion; all events occurred at rates ≤1%. The incidence of adverse reactions associated with ARNUITY ELLIPTA 100 mcg is shown in Table 1 and is based on one 24-week trial (Trial 1) in adult and pediatric subjects aged 12 years and older with asthma.
Table 1. Adverse Reactions with ARNUITY ELLIPTA 100 mcg with ≥3% Incidence and More Common than Placebo (Trial 1, Intent-to-Treat Population) Adverse Reaction ARNUITY ELLIPTA 100 mcg (n = 114) % Placebo (n = 115) % Nasopharyngitis 8 5 Bronchitis 7 6 Upper respiratory tract infection 6 5 Headache 6 4 Pharyngitis 4 3 Sinusitis 4 <1 Toothache 3 <1 Gastroenteritis viral 3 0 Oral candidiasis 3 0 Oropharyngeal candidiasis 3 0 Oropharyngeal pain 3 0 The incidence of adverse reactions associated with ARNUITY ELLIPTA 200 mcg is shown in Table 2 and is based on one 24-week trial (Trial 3) in adult and pediatric subjects aged 12 years and older with asthma.
This trial did not have a placebo arm. Table 2. Adverse Reactions with ARNUITY ELLIPTA 200 mcg with ≥3% Incidence (Trial 3, Safety Population) Adverse Reaction ARNUITY ELLIPTA 200 mcg (n = 119) % ARNUITY ELLIPTA 100 mcg (n = 119) % Nasopharyngitis 13 12 Headache 13 10 Bronchitis 7 12 Influenza 7 4 Upper respiratory tract infection 6 2 Sinusitis 4 7 Oropharyngeal pain 4 3 Pharyngitis 3 6 Back pain 3 3 Dysphonia 3 2 Oral candidiasis 3 <1 Procedural pain 3 <1 Rhinitis 3 <1 Throat irritation 3 <1 Abdominal pain 3 0 Cough 3 0 Adverse reactions observed in the other trials were consistent with those described in Tables 1 and 2.
Long-term Safety Long-term safety data are based on 2 trials in adult and pediatric subjects aged 12 years and older with asthma. In one 52-week trial, subjects received fluticasone furoate 100 mcg (n = 201) or fluticasone furoate 200 mcg (n = 202) in combination with a LABA. Subjects had a mean age of 39 years (pediatric patients 12 years and older made up 16% of the population), 63% were female, and 67% were Caucasian.
In addition to the events shown in Table 1 and Table 2 , adverse events occurring in ≥3% of the subjects treated with fluticasone furoate 100 mcg or fluticasone furoate 200 mcg, in combination with a LABA, included pyrexia, extrasystoles, upper abdominal pain, respiratory tract infection, diarrhea, and allergic rhinitis. In a second 24- to 76-week trial, subjects received fluticasone furoate 100 mcg (n = 1,010). Subjects 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 within the previous 12 months.
Subjects had a mean age of 42 years (pediatric patients 12 years and older made up 14% of the population), 67% were female, and 73% were Caucasian. In addition to the events shown in Table 1 and Table 2 , adverse events occurring in ≥3% of subjects treated with fluticasone furoate 100 mcg for up to 76 weeks included allergic rhinitis, nasal congestion, and arthralgia. Pediatric Subjects Aged 5 to 11 Years The safety data for pediatric subjects is based upon one 12-week clinical trial that enrolled 593 subjects with asthma aged 5 to 11 years.
Dosages of fluticasone furoate studied were 25, 50, or 100 mcg administered once daily. ARNUITY ELLIPTA 50 mcg was studied in 120 subjects (46 females and 74 males) [see Clinical Studies ( 14.2 )] . Adverse reactions (≥3% and greater than placebo) seen in pediatric subjects were similar to those reported in adult and pediatric subjects aged 12 years and older. Adverse reactions occurring in ≥3% of subjects treated with ARNUITY ELLIPTA 50 mcg and greater than placebo were pharyngitis, bronchitis, and viral infection.
6.2Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of ARNUITY ELLIPTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to ARNUITY ELLIPTA or a combination of these factors.
Immune System Disorders Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria.
