A study of patients in Asia with chronic obstructive pulmonary disease (COPD) found that aclidinium was associated with clinically meaningful bronchodilation and that aclidinium/formoterol provided greater bronchodilation vs monotherapies in patients with stable moderate to severe disease. Study findings were reported in Respiratory Medicine.
The phase 3, randomized, parallel-group AVANT study (ClinicalTrials.gov Identifier: NCT03022097) investigated aclidinium/formoterol and its monocomponents in a population of patients living in Asia (ie, China, India, Philippines, Taiwan, and Vietnam) who had moderate to severe COPD.
The 24-week study enrolled patients from February 2, 2017, to April 14, 2022. Patients were randomly assigned 1:1:1:1 to aclidinium/formoterol 400/12 µg, aclidinium 400 µg, formoterol 12 µg, or placebo. Eligible patients were aged 40 years or older, currently or formerly smoked (≥10 pack-years smoking history), and had a diagnosis of stable moderate to severe COPD.
The primary endpoints were change at week 24 in 1-hour morning postdose forced expiratory volume in 1 second (FEV1) with aclidinium/formoterol vs aclidinium; morning predose (trough) FEV1 with aclidinium/formoterol vs formoterol; and trough FEV1 with aclidinium vs placebo.
In patients from Asia with moderate-to-severe, stable COPD, aclidinium provided clinically meaningful bronchodilation vs placebo while aclidinium/formoterol provided higher bronchodilation than monotherapies.
A total of 1066 patients were randomly assigned to receive aclidinium/formoterol (n=265), aclidinium (n=267), formoterol (n=265), or placebo (n=269). The mean age in the 4 groups was 64.9 to 65.4 years, more than 95% of participants were male, and about 70% were from China.
Aclidinium/formoterol was associated with greater improvement at week 24 in 1-hour morning postdose FEV1 vs aclidinium (least squares [LS] mean, 92 mL; 95% CI, 60-124; P <.001). Aclidinium monotherapy also led to improved 1-hour morning postdose FEV1 at week 24 vs placebo.
Morning predose (trough) FEV1 improved with aclidinium/formoterol vs formoterol (LS mean, 85 mL; 95% CI, 53-117; P <.001) and with aclidinium compared with placebo (LS mean, 134 mL; 95% CI, 103-166; P <.001). Aclidinium monotherapy also was associated with improved morning predose (trough) FEV1 at week 24 vs placebo.
At week 24, improvement in transition dyspnea index focal score was greater for aclidinium/formoterol vs placebo (LS mean, 0.8; 95% CI, 0.2-1.3; P =.005) and the LS mean difference for aclidinium vs placebo was 0.4 (95% CI, −0.1 to 1.0; P =.132).
Treatment-emergent adverse events (TEAEs) were comparable among the treatment groups (aclidinium/formoterol, 54.8%; aclidinium, 47.4%; formoterol fumarate, 53.4%; placebo, 53.9%). Treatment-emergent serious adverse event rates were low and similar among groups, as was the proportion of patients who had a TEAE that led to drug discontinuation.
Among several limitations, the study was conducted during the COVID-19 pandemic, which resulted in disruption to enrollment, and most participants were male. Also, the patients spent much more time at home during the pandemic, where exposure to exacerbation triggers was limited, and the study was not powered for the evaluation of exacerbation rates among treatment groups.
“In patients from Asia with moderate-to-severe, stable COPD, aclidinium provided clinically meaningful bronchodilation vs placebo while aclidinium/formoterol provided higher bronchodilation than monotherapies,” the study authors concluded. “The results of this study extend the existing knowledge about aclidinium/formoterol and aclidinium to the Asian population,” the investigators added.
Disclosure: This study was sponsored by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.