Efficacy and safety of TQC3403 in patients with chronic obstructive pulmonary disease (COPD): a multicenter, randomized, open-label, phase 3 equivalence trial

Background: Although dual bronchodilators represent the cornerstone of pharmacological therapy for chronic obstructive pulmonary disease (COPD), few affordable generic products are available worldwide. This study aimed to evaluate the clinical equivalence between TQC3403 [the first generic umeclidinium/vilanterol (UMEC/VI) dry powder inhaler (DPI)] and ANORO^®.

Methods: This multicenter, randomized, open-label, phase 3 equivalence trial was conducted at 56 centers in China. Eligible patients with moderate-to-severe COPD were randomized in a 1:1 ratio to receive either TQC3403 or ANORO^® for 24 weeks. The primary efficacy endpoint was the change in trough forced expiratory volume in 1 second (FEV1) from baseline to week 24, with the equivalence interval set at ±70 mL. A mixed-effects model for repeated measures (MMRM) was used to evaluate the primary efficacy endpoint, presented as least squares mean (LSM) difference and its 95% confidence interval (CI). Secondary efficacy endpoints included peak FEV₁ on day 1 and at week 24, trough FEV1 at weeks 4, 8, 12, and 18, COPD Assessment Test (CAT) score at week 24, incidence of moderate-to-severe acute exacerbations of COPD (AECOPD), average use of rescue medication, and percentage of days without rescue medication use. Safety outcomes included adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs).

Results: A total of 414 patients were enrolled, with 207 in each group. Baseline demographic and clinical characteristics of the two groups were similar. The LSM difference in the change in trough FEV₁ from baseline to week 24 was 16 mL (95% CI: −30 to 62; P=0.49), entirely within the equivalence interval. The LSM differences in the change in peak FEV₁ within 3 hours post-administration on day 1 and at week 24 were 8 mL (95% CI: −22 to 38; P>0.05) and 23 mL (95% CI: −29 to 74; P>0.05). The mean changes in CAT score were −4.1±5.91 in TQC3403 group and −4.1±5.15 in generic ANORO^® group (P=0.97). The incidence of moderate-to-severe AECOPD was 4.35% in TQC3403 group and 2.42% in ANORO^® group (P=0.28). Safety and tolerability profile was comparable between two groups.

Conclusions: TQC3403 demonstrated clinical equivalence to ANORO^® with respect to efficacy, safety, and tolerability in patients with COPD, supporting its clinical use as an effective and well-tolerated alternative for this population.

Trial registration: The clinical research was registered at Chinese Clinical Trial Register (Ref: ChiCTR2600120078).