ADVAIR DISKUS (Page 5 of 12)
6.2 Clinical Trials Experience in Chronic Obstructive Pulmonary Disease
Short-term (6 Months to 1 Year) Trials
The short-term safety data are based on exposure to ADVAIR DISKUS 250/50 twice daily in one 6-month and two 1-year clinical trials. In the 6-month trial, a total of 723 adult subjects (266 females and 457 males) were treated twice daily with ADVAIR DISKUS 250/50, fluticasone propionate inhalation powder 250 mcg, salmeterol inhalation powder, or placebo. The mean age of the subjects was 64, and the majority (93%) was Caucasian. In this trial, 70% of the subjects treated with ADVAIR DISKUS reported an adverse reaction compared with 64% on placebo. The average duration of exposure to ADVAIR DISKUS 250/50 was 141.3 days compared with 131.6 days for placebo. The incidence of adverse reactions in the 6-month trial is shown in Table 3.
| Adverse Event | ADVAIR DISKUS 250/50 (n = 178) % | Fluticasone Propionate 250 mcg (n = 183) % | Salmeterol 50 mcg (n = 177) % | Placebo (n = 185) % |
| Ear, nose, and throat | ||||
| 10 | 6 | 3 | 1 |
| 8 | 5 | 4 | 7 |
| 5 | 3 | <1 | 0 |
| 3 | 8 | 5 | 3 |
| Lower respiratory | ||||
| 6 | 4 | 3 | 3 |
| Neurology | ||||
| 16 | 11 | 10 | 12 |
| 4 | <1 | 3 | 2 |
| Non-site specific | ||||
| 4 | 3 | 0 | 3 |
| 3 | 2 | 2 | 3 |
| Musculoskeletal | ||||
| 9 | 8 | 12 | 9 |
| 3 | 3 | 1 | 1 |
In the two 1-year trials, ADVAIR DISKUS 250/50 was compared with salmeterol in 1,579 subjects (863 males and 716 females). The mean age of the subjects was 65 years, and the majority (94%) was Caucasian. To be enrolled, all of the subjects had to have had a COPD exacerbation in the previous 12 months. In this trial, 88% of the subjects treated with ADVAIR DISKUS and 86% of the subjects treated with salmeterol reported an adverse event. The most common events that occurred with a frequency of >5% and more frequently in the subjects treated with ADVAIR DISKUS were nasopharyngitis, upper respiratory tract infection, nasal congestion, back pain, sinusitis, dizziness, nausea, pneumonia, candidiasis, and dysphonia. Overall, 55 (7%) of the subjects treated with ADVAIR DISKUS and 25 (3%) of the subjects treated with salmeterol developed pneumonia.
The incidence of pneumonia was higher in subjects older than 65 years, 9% in the subjects treated with ADVAIR DISKUS compared with 4% in the subjects treated with ADVAIR DISKUS younger than 65 years. In the subjects treated with salmeterol, the incidence of pneumonia was the same (3%) in both age groups. [See Warnings and Precautions (5.5), Use in Specific Populations (8.5).]
Long-term (3 Years) Trial
The safety of ADVAIR DISKUS 500/50 was evaluated in a randomized, double-blind, placebo-controlled, multicenter, international, 3-year trial in 6,184 adult subjects with COPD (4,684 males and 1,500 females). The mean age of the subjects was 65 years, and the majority (82%) was Caucasian. The distribution of adverse events was similar to that seen in the 1-year trials with ADVAIR DISKUS 250/50. In addition, pneumonia was reported in a significantly increased number of subjects treated with ADVAIR DISKUS 500/50 and fluticasone propionate 500 mcg (16% and 14%, respectively) compared with subjects treated with salmeterol 50 mcg or placebo (11% and 9%, respectively). When adjusted for time on treatment, the rates of pneumonia were 84 and 88 events per 1,000 treatment-years in the groups treated with fluticasone propionate 500 mcg and with ADVAIR DISKUS 500/50, respectively, compared with 52 events per 1,000 treatment-years in the salmeterol and placebo groups. Similar to what was seen in the 1-year trials with ADVAIR DISKUS 250/50, the incidence of pneumonia was higher in subjects older than 65 years (18% with ADVAIR DISKUS 500/50 versus 10% with placebo) compared with subjects younger than 65 years (14% with ADVAIR DISKUS 500/50 versus 8% with placebo). [See Warnings and Precautions (5.5), Use in Specific Populations (8.5).]
Additional Adverse Reactions
Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that were reported more frequently by subjects with COPD treated with ADVAIR DISKUS compared with subjects treated with placebo include the following: syncope; ear, nose, and throat infections; ear signs and symptoms; laryngitis; nasal congestion/blockage; nasal sinus disorders; pharyngitis/throat infection; hypothyroidism; dry eyes; eye infections; gastrointestinal signs and symptoms; oral lesions; abnormal liver function tests; bacterial infections; edema and swelling; viral infections.
Laboratory Abnormalities
There were no clinically relevant changes in these trials. Specifically, no increased reporting of neutrophilia or changes in glucose or potassium was noted.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.