Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 versus reference denosumab in healthy males: A randomized phase I study.

Denosumab is a human IgG2 monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) for the treatment of osteoporosis and bone loss. HLX14 is a proposed biosimilar of denosumab. This randomized, parallel-group, two-part, phase I study aimed to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 with reference denosumab in Chinese healthy adult male participants. In Part 1, participants were randomized 1:1 and given HLX14 or reference denosumab sourced from the European Union (EU). In double-blind Part 2, participants were randomized 1:1:1:1 to receive HLX14 or denosumab sourced from the United States, EU, or China. All study drugs were administered via subcutaneous injection at a single dose of 60 mg. The primary endpoints were area under the serum drug concentration-time curve from time 0 to the last concentration-quantifiable time t (AUC0-t), maximum serum drug concentration (Cmax), and area under the serum drug concentration-time curve from time 0 to infinity (AUC0-inf). Twenty-four participants were randomized in Part 1 and 228 in Part 2. The 90% confidence intervals of geometric mean ratio of AUC0-t, Cmax, and AUC0-inf between HLX14 and denosumab from different sources fell within the pre-specified similarity margins of 0.80-1.25 (AUC0-t, 0.91-1.13; Cmax, 0.91-1.13; AUC0-inf, 0.91-1.12), demonstrating pharmacokinetic similarity. No notable difference was observed among treatment groups in pharmacodynamics, safety, or immunogenicity. HLX14 demonstrated highly similar pharmacokinetic characteristics with comparable pharmacodynamics, safety, and immunogenicity to denosumab, supporting its further investigation as a potential denosumab biosimilar.

Li N ，Chu N ，Zhu L ，Wu X ，Wei Q ，Wang J ，Hu X ，Yu H ，Wang Q ，Yuan W ，Huang K ，Zhang J ... -  《-》

The Totality of Evidence for SDZ-deno: A Biosimilar to Reference Denosumab.

Vogg B ，Poetzl J ，Schwebig A ，Sekhar S ，Kivitz A ，Krivtsova N ，Renner O ，Body JJ ，Eastell R ... -  《-》

A three-arm clinical study to compare pharmacokinetic and pharmacodynamic similarity of the denosumab biosimilar LY06006 with reference denosumab in healthy male subjects.

Fuhr R ，Sun X ，Wang X ，Dong Y ，Tai J ，Zhou M ，Dou C ... -  《-》

Pharmacokinetics and Bioequivalence of Two Powders of Azithromycin for Suspension: A Nonblinded, Single-Dose, Randomized, Three-Way Crossover Study in Fed and Fasting States Among Healthy Chinese Volunteers.

Azithromycin, a macrolide antibiotic, is commonly used to treat mild-to-moderate bacterial infections. This research aimed to evaluate the pharmacokinetics (PK) properties and bioequivalence (BE) of two azithromycin (EQ 100 mg base/packet) powders for suspension in Chinese healthy participants in fed and fasting conditions. A total of 90 Chinese healthy participants were enrolled in this nonblinded, single-dose, randomized, semireplicate, three-period, three-sequence, crossover study. Of them, 42 and 40 were categorized to the fed and fasting conditions, respectively. The washout period between doses was 21 days. Blood specimens were harvested prior to administering the drug and 194 h following administration. The plasma levels of azithromycin were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach. PK parameters were measured using noncompartmental analysis. This research compared BE between the reference and test products using the average bioequivalence (ABE) or reference-scaled average bioequivalence (RSABE) method, considering the within-subject variability (SWR) of the reference preparation. Adverse events (AEs) were monitored to examine safety and tolerability. The RSABE method (SWR ≥ 0.294) was used to determine the BE of maximal plasma concentration (Cmax) in both fed and fasting conditions. In the ABE approach, (SWR < 0.294) was adopted to assess the BE of the area under the plasma concentration-time curve from time zero to the last measurable time point (AUC0-t) and determine the area under the plasma concentration time curve from time zero to time infinity (AUC0-inf). In the fasting condition, the point estimate of the test/reference ratio for Cmax was 1.08, with a 95% upper confidence bound of - 0.05 < 0.00. The geometric mean ratio (GMRs) for AUC0-t and AUC0-inf was 115.21% [90% confidence interval (CI) 107.25-123.27%] and 113.07% (90% CI 105.14-121.61%), respectively. In the fed condition, the point estimate of the test/reference ratio for Cmax was 0.94, with a 95% upper confidence bound of - 0.10 < 0.00. The GMR for AUC0-t and AUC0-inf was 99.51% (90% CI of 91.03-108.78%) and 99.43% (90% CI 91.73-107.78%), respectively. These data all satisfied the BE criteria for drugs with high variability. All AEs were transient and mild, and no severe AEs were observed. Our study indicated that the test and reference products of azithromycin (EQ 100 mg base/packet) powder for suspension were bioequivalent and safe in healthy Chinese participants, irrespective of the feeding condition. CLINICAL TRIAL REGISTRATION (CHINADRUGTRIALS.ORG.CN): CTR20232646, registered on 25 August 2023.

Shao J ，Liu X ，Lin J ，Chen J ，Xie X ... -  《-》

Pooled analysis of three pharmacokinetic studies comparing biosimilar MB02 and reference bevacizumab.

Miguel-Lillo B ，Sánchez-Vidaurre S ，Pérez Díaz L ，Paravisini A ... -  《Pharmacology Research &amp; Perspectives》