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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. [ABSTRACT FROM AUTHOR]

The supply of branded 6‐mercaptopurine (6‐MP) is limited in China, necessitating the local production and clinical evaluation of generic alternatives. We evaluated the in vivo bioequivalence (BE) of a new generic mercaptopurine tablet (50 mg) formulation by comparing peak plasma concentration and area under the concentration–time curve (AUC) with a branded 6‐MP formulation as the reference in 36 healthy fasting Chinese adults. The in vivo BE was evaluated by the average BE test. The safety parameters of the test and reference formulations were also evaluated. The geometric mean ratios for AUC over the dosing interval and AUC from time zero to infinity were 104% and 104%, respectively, of the reference values, while the point estimate of the geometric mean ratio for peak plasma concentration was 104% of the reference value. The test and reference formulations in this study were both deemed safe as only 23 Grade 1 adverse events were observed in 13 of 36 subjects. The test and reference formulations of 6‐MP tablets meet the regulatory criteria for BE in healthy fasting Chinese adults. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the bioequivalence and safety of test preparation sodium levofolinate injection with reference preparations of calcium levofolinate for injection and sodium folinate for injection in China. A single‐center, randomized, open‐label, 3‐period, crossover test was conducted on 24 healthy subjects. Plasma concentration of levofolinate, dextrofolinate, and their metabolites l‐5‐methyltetrahydrofolate and d‐5‐methyltetrahydrofolate were quantified by a validated chiral–liquid chromatography–tandem mass spectrometry method. All adverse events (AEs) were documented to evaluate safety as they occurred and evaluated descriptively. Pharmacokinetic parameters (maximum plasma concentration, time to maximum concentration, area under the plasma concentration–time curve over the dosing interval, area under the plasma concentration–time curve from time 0 to infinity, terminal elimination half‐life, and terminal rate constant) of 3 preparations were calculated. A total of 8 subjects (10 cases) of AEs occurred in this trial. No serious AEs or unexpected serious adverse reactions were observed. Sodium levofolinate was bioequivalent to calcium levofolinate and sodium folinate in Chinese subjects, and the 3 preparations were all well tolerated. [ABSTRACT FROM AUTHOR]

Romiplostim is approved for the treatment of immune thrombocytopenia (ITP). This study aimed to evaluate the pharmacokinetics, safety, and pharmacodynamics of romiplostim in Chinese patients with ITP. This multicenter, open‐label, dose‐escalation phase I/II trial enrolled ITP patients from 5 centers in China between October 2015 and August 2017. There were 2 cohorts: 1 μg/kg and 3 μg/kg weekly for 2 weeks. The end points included pharmacokinetics, platelet changes from baseline, hematological indicators, and adverse events (AEs). Sixteen participants, with 8 patients in each cohort, were enrolled. In the 1 μg/kg cohort, time to maximum concentration was 4.00 (4.00‐7.83) hours, maximum serum drug concentration was 52.0 (16.0‐228.0) pg/mL, and area under the serum drug concentration–time curve from time 0 to the last detectable time point was 389 (32.0‐5400) pg · h/mL. In the 3 μg/kg cohort, time to maximum serum drug concentration was 11.91 (4.00‐12.00) hours, maximum serum drug concentration was 105.0 (25.5‐313.0) pg/mL, and half‐life was 12.7 (8.2‐23.6) hours. The absolute change of peak platelet count from baseline was 14 (3‐40) and 72 (3–369) ×109/L in the 1 and 3 μg/kg cohorts, respectively. Seven (87.5%) and eight (100%) participants had treatment‐emergent AEs in 1 μg/kg cohort and 3 μg/kg cohort, respectively. No major AEs occurred in the 2 cohorts. Romiplostim (1 and 3 μg/kg) is safe and well tolerated in Chinese patients with ITP. [ABSTRACT FROM AUTHOR]

In patients with coronary heart disease undergoing primary prevention, hypertriglyceridemia is a residual risk for cardiovascular events. Omega‐3 carboxylic acid (OM3‐CA), a mixture of the free fatty acid forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be beneficial in reducing triglyceride levels. As part of the clinical development program of OM3‐CA in China, this phase I study evaluated the pharmacokinetics, safety, and tolerability profile of OM3‐CA in healthy subjects. The pharmacokinetic results of this study were also compared with those of available data for Western populations. Fourteen healthy Chinese subjects (aged 18‐45 years) received once‐daily oral OM3‐CA 4 g for 14 consecutive days. Pharmacokinetic parameters were assessed from both baseline‐uncorrected and baseline‐corrected plasma concentrations vs time profile of EPA, DHA, and EPA plus DHA. Following single and multiple oral doses of OM3‐CA, the absorption of EPA, DHA, and EPA plus DHA was steady with median tmax occurring at 5.5–6 hours after both single and multiple dosing. Close to steady‐state concentrations in plasma were reached after 14 days of continuous once‐daily dosing, and accumulation was confirmed for EPA, DHA, and EPA plus DHA. Of the 14 subjects treated with OM3‐CA, 6 (42.9%) reported at least 1 adverse event (diarrhea) during the study, which was determined as mild and treatment emergent. No serious adverse events were reported. In summary, the pharmacokinetic profile of oral OM3‐CA 4 g after single and multiple dosing in healthy Chinese subjects is consistent with that observed in other ethnic populations. [ABSTRACT FROM AUTHOR]