A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants.

Tozorakimab is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin (IL)-33, an IL-1 family cytokine. This phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study (NCT05070312) evaluated tozorakimab in a healthy Chinese population. Outcomes included the characterization of the pharmacokinetic (PK) profile and immunogenicity of tozorakimab. Safety outcomes included treatment-emergent adverse events (TEAEs) and clinical laboratory, electrocardiogram, and vital sign parameters. Healthy, non-smoking, male, and female Chinese participants aged 18-45 years with a body mass index 19-24 kg/m2 were enrolled. In total, 36 participants across 2 cohorts of 18 participants were randomized 2:1 to receive a single subcutaneous dose of tozorakimab (300 mg [2 mL] or 600 mg [4 mL]) or matching placebo (2 or 4 mL). Tozorakimab showed dose-dependent serum PK concentrations with an approximate monophasic distribution in serum over time and a maximum observed peak concentration of 20.1 and 33.7 µg/mL in the 300- and 600-mg cohorts, respectively. No treatment-emergent anti-drug antibodies for tozorakimab were observed in any of the participants. There were no clinically relevant trends in the occurrence of TEAEs across the treatment groups. There were no clinically relevant trends over time in clinical laboratory (hematology, clinical chemistry, and urinalysis), electrocardiogram, or vital sign parameters in any treatment group. Overall, tozorakimab demonstrated dose-dependent systemic exposure in healthy Chinese participants and was well tolerated, with no safety concerns identified in this study.

Long-term safety of aclidinium bromide/formoterol fumarate fixed-dose combination: Results of a randomized 1-year trial in patients with COPD.

TRIAL DESIGN: This was a one-year, Phase III randomized, double-blind, parallel-group, active-control study investigating the long-term safety and tolerability of twice-daily aclidinium 400 µg/formoterol 12 µg versus formoterol 12 µg. METHODS: Eligible patients were male or female, current or ex-smokers (history of ≥10 pack-years) aged ≥40 years with a diagnosis of moderate to severe chronic obstructive pulmonary disease (COPD): post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <70%, and post-bronchodilator FEV1≥30% and <80% predicted. Patients were randomized 2:1 to twice-daily aclidinium 400 µg/formoterol 12 µg or formoterol 12 µg, administered via a multidose dry powder inhaler (Genuair™/Pressair(®))(1). The objective was to evaluate the one-year safety of aclidinium 400 µg/formoterol 12 µg versus formoterol 12 µg. RESULTS: All 590 patients were included in the safety population; 392 patients received aclidinium 400 µg/formoterol 12 µg and 198 patients received formoterol 12 µg. Of these, 581 patients were included in the intent-to-treat (ITT) population (385 patients received aclidinium 400 µg/formoterol 12 µg; 196 patients received formoterol 12 µg). In the safety population, the percentage of patients with ≥1 treatment-emergent adverse event was similar between aclidinium 400 µg/formoterol 12 µg (71.4%) and formoterol 12 µg (65.7%). Mean baseline post-bronchodilator FEV1 was 51.3% of predicted (ITT population). Aclidinium 400 µg/formoterol 12 µg significantly improved morning pre-dose (trough) FEV1 and trough FVC versus formoterol 12 µg at each assessment, with improvements at Week 1 (least squares mean difference [LSMD]: 87.4 mL and 157.8 mL, respectively) maintained at study end (LSMD: 81.5 mL and 185.4 mL, respectively). CONCLUSIONS: Aclidinium 400 µg/formoterol 12 µg was well tolerated, with a safety profile similar to formoterol 12 µg and consistent with that seen in two Phase III studies. Additionally, aclidinium 400 µg/formoterol 12 µg improved lung function versus formoterol 12 µg, with a sustained effect over one year.