PURPOSE: The safety and tolerability profile associated with the long-term use of mometasone furoate/formoterol (MF/F) combination therapy administered via metered-dose inhaler for treatment of chronic obstructive pulmonary disease (COPD) has not been elucidated. We report pooled safety and tolerability findings from 2 independent 52-week clinical trials conducted to characterize the use of twice-daily (BID) inhaled MF/F 400/10µg and 200/10µg in moderate−very severe COPD.
METHODS: Two multicenter, double-blind, placebo (PBO)-controlled trials were conducted in current or ex-smokers (≥10 pack-yrs) with a ≥2 yr history of moderate−very severe COPD (≥40 yrs) (prebronchodilator FEV1/forced vital capacity ratio ≤0.7 and postbronchodilator FEV1 ≤60% predicted). Subjects were randomized to BID MF/F 400/10µg (n=442), MF/F 200/10µg (n=446), MF 400µg (n=463), F 10µg (n=452), or PBO (n=448). After 26 wks, all subjects randomized to PBO were discontinued, and 75% of subjects randomized to an active treatment were randomly selected to participate in a 26-wk double-blind safety extension period. The current analysis evaluated pooled safety outcomes among all randomized subjects in the 4 active treatment groups.
RESULTS: At the 26 wk time point, the pooled incidence of treatment-related adverse events (TRAEs) for the MF/F 400/10µg, MF/F 200/10µg, MF 400µg, F 10µg, and PBO groups was 7.2%, 4.9%, 8.0%, 7.5%, and 5.4%, respectively. For the entire 52 wks of active treatment, the pooled incidence of TRAEs in the MF/F 400/10µg, MF/F 200/10µg, MF 400µg, and F 10µg groups was 9.0%, 7.0%, 10.2%, and 8.2%, respectively. The most common TRAEs across all active treatment groups over 52 wks were oral fungal infection (1.2%) and cataracts and lenticular opacity (1.4%). Exposure-adjusted rates of serious AEs for each active treatment group were 16.8, 12.1, 16.6, and 16.2 events/100 subject-yrs for MF/F 400/10µg, MF/F 200/10µg, MF 400µg, and F 10µg, respectively. The exposure adjusted pneumonia (including all types) and mortality rates over the 52-wk period were 3.7, 1.2, 2.1 and 2.4 events/100 subject-yrs and 2.8, 0.9, 2.4, and 4.2 events/100 subject-yrs, respectively.
CONCLUSIONS: During 1 year of treatment, there were no notable differences in the incidence or types of AEs between the MF/F 400/10µg BID and MF/F 200/10µg BID groups compared with the MF or F groups. Rates of pneumonia were low across all treatment groups.
CLINICAL IMPLICATIONS: MF/F 400/10µg BID and MF/F 200/10µg BID are well tolerated in subjects with moderate−very severe COPD.
DISCLOSURE: Carlos Eduardo Matiz-Bueno: Other: Spouse is an employee of Merck
Dennis Doherty: University grant monies: Boehringer Ingelheim, Merck, Novartis, Pfizer, Grant monies (from sources other than industry): NIH-NHLBI, Department of Veterans Affairs, Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca, Boehringer Ingelheim, Forest, Ikaria, Merck, Pfizer
Edward Kerwin: Grant monies (from industry related sources): Merck
Donald Tashkin: University grant monies: Merck, Consultant fee, speaker bureau, advisory committee, etc.: Merck
Tulin Shekar: Employee: Merck
Sibabrata Banerjee: Employee: Merck
Jonathan Sadeh: Employee: Merck
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