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

Abstract

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.

Safety of long acting muscarinic antagonists: are all these drugs always and equally safe?

“…Severe adverse events during the treatment period were reported in nine patients (7%) but none were considered to be drugrelated. Increased blood bilirubin was recognized in one patient due to UMEC 6 . UMEC is a substrate of cytochrome P450 2D6 and it is mainly metabolized in the liver.…”

“…Both aclidinium and umeclidinium can be used in renal impairment 1 . Yamagata et al 6 reported a dropout rate of 15%, an expected percentage in a fragile population for a trial of 52 weeks' duration. The main causes of withdrawal were exacerbations and pneumonia, consistent with previous studies 1 .…”

“…The study by Yamagata et al 6 UMEC at the unapproved dose of 125 mg OD as primary endpoint in 131 Japanese patients with COPD 6 . The authors observed that some subjects have suffered from constipation (N ¼ 11, 8%), thirst (2%), dry eye (<1%) and urinary retention (<1%).…”

“…The main causes of withdrawal were exacerbations and pneumonia, consistent with previous studies 1 . Pneumonia was observed in 12 cases; 11 out of 12 were taking either ICS/LABA or ICS alone 6 . The use of ICS is associated with the risk of pneumonia in COPD subjects, mainly in the emphysematous type 8 , prevalent in the enrolled population from Yamagata (88% of total) 6 .…”

“…Pneumonia was observed in 12 cases; 11 out of 12 were taking either ICS/LABA or ICS alone 6 . The use of ICS is associated with the risk of pneumonia in COPD subjects, mainly in the emphysematous type 8 , prevalent in the enrolled population from Yamagata (88% of total) 6 . Nevertheless, only in three cases was pneumonia considered a severe adverse event.…”