Clinical Pharmacology in Drug Development最新文献

This study aimed to evaluate the pharmacokinetics, bioequivalence, and safety for two formulations of acetylcysteine granules in healthy Chinese subjects under fasting and postprandial conditions. A single-center, randomized, open-label, single-dose, two-period, two-sequence crossover study was performed. 34 and 38 healthy Chinese volunteers were enrolled in the fasting and postprandial groups, respectively. Each subject received a single oral dose (0.2 g) of acetylcysteine granules per period either as the test (T) or reference (R) formulation, followed by a 5-day washout interval. Serial blood samples were collected for up to 24 h post-dose in each period, and plasma concentration of acetylcysteine was detected using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Whether under fasting or postprandial conditions, all the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for maximum concentration (C_max), area under the curve from time 0 to the time of the last measurable concentration (AUC_0-t), and area under the curve from time 0 to infinity (AUC_0-∞) were all found to fall within the bioequivalence range of 80.00-125.00%. Only mild adverse events (AEs) were observed. In the study, the two formulations of acetylcysteine granules were bioequivalent and safe.

This 2-part, randomized, placebo-controlled, double-blind, Phase 1 study analyzed the pharmacokinetics, safety, and biomarker profile of fezolinetant in healthy Japanese individuals. Part 1: male participants received single doses of placebo or fezolinetant 15 or 60 mg. Part 2: male and premenopausal and postmenopausal female participants received a single dose of placebo or fezolinetant 180 mg, followed by a 2-day washout, and multiple dosing once daily for 10 days. Fezolinetant was rapidly absorbed with peak concentrations 1-2 hours after single-dose administration; plasma levels subsequently declined (half-life range, 3.29-7.24 hours). Only slight accumulation (area under the concentration–time curve accumulation ratio, 1.46-1.57) was observed after once-daily multiple-dose administration. No serious/severe treatment-emergent adverse events were observed; the only fezolinetant-related treatment-emergent adverse event was mild uterine bleeding in 1 premenopausal woman and 1 postmenopausal woman. Concentration-QT analysis showed that fezolinetant does not have a clinically significant effect on QT interval. Fezolinetant produced dose-dependent reductions in luteinizing hormone and slight reductions in follicle-stimulating hormone; levels subsequently returned to baseline 48 hours or fewer after dosing. This analysis shows that fezolinetant doses up to 180 mg had an acceptable safety, pharmacokinetic, and biomarker profile. This study clarifies the safety, pharmacokinetic, and biomarker profiles of fezolinetant in Japanese individuals.

Galcanezumab is used in several regions, including the United States, Europe, and China, as a preventive treatment for migraine. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PK) of galcanezumab in healthy Chinese participants. In this phase I single-dose study, 30 healthy adults were assigned to one of the two cohorts (120 or 240 mg) and randomized in a 4:1 ratio to receive a single subcutaneous (SC) dose of galcanezumab or placebo. Overall, 29 (96.7%) participants reported 93 treatment-emergent adverse events (TEAEs), with 21 participants reporting 44 TEAEs related to the study treatment. Most study-related TEAEs (95%) were mild in severity. The most commonly reported TEAE was upper respiratory tract infection. The PK data demonstrated that maximum observed drug concentration (C_max) and area under the serum concentration curve from time zero to infinity increased proportionally to dose, with an apparent clearance of 0.009 L/h and a terminal elimination half-life (t_1/2) of 27 days. Galcanezumab was safe and well tolerated and demonstrated a PK profile consistent with that of non-Chinese populations, supporting its use for the preventive treatment of migraine in Chinese patients.

HR19042 is a novel, orally administered, targeted-release formulation of the topically active corticosteroid budesonide, developed to release active drug within the terminal ileum and indicated to reduced estimated glomerular filtration rate loss in adults with primary immunoglobulin A nephropathy. This randomized, single-dose, open-label, six-sequence, three-treatment crossover trial aimed to explore the pharmacokinetic (PK) of HR19042 in comparison with two other budesonide targeted-release formulations among healthy Chinese subjects. Plasma budesonide concentrations were measured via liquid chromatography with tandem mass spectrometry, and PK parameters were analyzed using non-compartmental methods. Eighteen subjects successfully completed the trial. The median T_lag and T_max of HR19042 were 1.25 and 3.50 h shorter than those of Nefecon, respectively. The C_max of HR19042 was approximately 1.9-fold higher than that of Nefecon and 1.4-fold higher than that of Budenofalk. Based on the AUC_0-t determination, the relative bioavailability (F) of HR19042 was approximately 136.93% relative to Nefecon and 129.68% relative to Budenofalk. In vitro, the dissolution of HR19042 occurred 30 min earlier than that of Nefecon in the intestinal buffer medium. In conclusion, both in vivo and in vitro findings suggest that HR19042 exhibits a faster absorption rate and higher oral bioavailability.

This study assessed the pharmacokinetics (PK) and bioequivalence (BE) of valsartan and amlodipine (80/5 mg) tablets in healthy Chinese subjects under fasting and fed conditions. A randomized, open-label, four-period crossover trial was conducted, with participants receiving test (T) or reference (R) formulations in cycles separated by a 14-day washout. Plasma concentrations of valsartan and amlodipine were measured using high-performance liquid chromatography-tandem mass spectrometry. PK parameters were analyzed noncompartmentally, and BE was evaluated using reference-scaled average bioequivalence (RSABE) for high-variability parameters (CV_W ≥ 30%) and average bioequivalence (ABE) for low-variability parameters (CV_W < 30%). Under fasting conditions, the maximum concentration of drug in blood plasma (C_max) of valsartan was assessed using RSABE methodology and demonstrated bioequivalence. For amlodipine, bioequivalence was established through conventional ABE analysis, with the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of C_max, AUC_0-t, and AUC_0-∞ all residing within the predefined equivalence boundaries. Under postprandial conditions, both drugs met BE criteria using ABE, with 90% CIs of GMRs within the acceptable range. Importantly, postprandial administration resulted in a significant reduction of approximately 30% in systemic exposure of valsartan for both test and reference formulations. All adverse events were mild and transient. The T and R formulations demonstrated bioequivalence and were well tolerated, supporting their interchangeability.

Tamsulosin is a highly selective α1A adrenergic receptor antagonist that can relax smooth muscles in the urethra, bladder neck, and prostate and improve urinary disorders. It is therefore widely used to treat lower urinary tract symptoms caused by benign prostatic hyperplasia. The aim of this study is to evaluate the pharmacokinetic (PK) characteristics and bioequivalence of 2 different formulations (tamsulosin sustained-release tablets and tamsulosin sustained-release capsules) in healthy Chinese subjects. This study was a single-center, randomized, open label, 2-formulation, single-administration, 2-cycle, double-crossover fasting/postprandial bioequivalence trial that included 56 healthy volunteers (28 fasting and 28 postprandial). Blood samples were collected from volunteers after oral administration, plasma concentrations of tamsulosin were determined by liquid chromatography-tandem mass spectrometry for PK analysis, and the safety and tolerability of the drug were monitored. Under fasting and postprandial conditions, the 90% confidence intervals for maximum observed concentration (C_max) and area under the plasma concentration-time curve from time 0 to the last sampling time (AUC_0-t) of the test and reference formulations were within an acceptable range (80%-125%). All adverse events (AEs) were mild and no serious AEs were observed in the study. The subject formulation of tamsulosin extended-release tablets was safe and well tolerated in healthy Chinese Volunteers.

Epilepsy is one of the most severe neurological disorders in the world, which might seriously endanger the lives of patients. Phenobarbital is an important medicine clinically used for the treatment of epilepsy, and it is irreplaceable in the treatment of generalized tonic–clonic seizures, focal seizures, status epilepticus, and pediatric epilepsy. However, the original research medicine of phenobarbital has not been launched in China. Therefore, an economical and effective generic medicine is of great significance to patients. In this study, a single-center, randomized, open-label, single-dose, two-formulation, two-period, two-sequence crossover design and parallel design were adopted. The phenobarbital tablets produced by Shandong Xinhua Pharmaceutical Co., Ltd. were used as the test formulation, and Phenobal produced by Fujinaga Pharmaceutical Co., Ltd. was used as the reference formulation for a bioequivalence study. Additionally, the influence of food on the pharmacokinetic parameters al was investigated. The results showed that the test formulation and the reference formulation were bioequivalent, and food might reduce the C_max (maximum concentration) and exposure of phenobarbital. This study provides data support for the marketing of generic phenobarbital medicines and offers a theoretical basis for the rational administration of phenobarbital. The clinical trial was registered in Chinese Clinical Trial Registry (Registration numbers: CTR20242404 and CTR20244155).

DATE: September 14, 2025

TIME: 5:00 – 7:00 PM

DATE: September 15, 2025

TIME: 5:00 – 7:00 PM

Safety, pharmacokinetics, and impact of race of pharmacokinetics on monoclonal antibodies tixagevimab and cilgavimab (AZD7442) were assessed in Chinese adult participants in a Phase 2, randomized, double-blind, placebo-controlled trial. In total, 272 participants were randomized 3:1 to a single intravenous dose of 600 mg AZD7442 or placebo and followed for 451 days. Mean participant age was 34.2 years, 5.9% were aged greater than 60 years, and 69.1% were male. Adverse events (AEs) occurred in 72.8% and 80.0% of participants with AZD7442 and placebo, respectively; most were mild or moderate in severity. Serious AEs were reported in 3.0% and 4.3% of participants with AZD7442 and placebo, respectively. No AEs of special interest, infusion-related reactions, or deaths occurred. Maximum serum concentrations of tixagevimab and cilgavimab were rapidly achieved following infusion, then declined through Day 361. Mean half-lives were 85 days for tixagevimab and 80 days for cilgavimab. AZD7442 recipients exhibited greater than 4-fold neutralizing antibody titer increases versus baseline at Day 8, which then declined through Day 361. Among AZD7442 recipients, 20.8% were treatment-emergent antidrug antibody positive. Asian race had no clinically significant impact on AZD7442 pharmacokinetics. Overall, intravenous 600 mg AZD7442 was well tolerated in Chinese adult participants. AZD7442 pharmacokinetics were similar in Asian and non-Asian participants.

ClinicalTrials.gov identifier: NCT05184062

Zanubrutinib is a next-generation Bruton tyrosine kinase inhibitor approved for treating B-cell malignancies. Two phase 1 studies evaluated a new 160-mg zanubrutinib tablet versus 80-mg capsules. In study BGB-3111-115 (n = 43), a randomized 3-period crossover trial, relative bioavailability and food effects were assessed. Under fasted conditions, systemic exposure (area under the concentration-time curve [AUC]) was comparable between tablets and capsules at both 160- and 320-mg doses. A high-fat meal increased tablet maximum plasma concentration (C_max) by 47%-79% but had minimal effect on AUC (<18%), supporting administration with or without food. Study BGB-3111-114 (n = 58) was a randomized, replicate crossover study that evaluated bioequivalence (BE) under fasted conditions. Geometric mean ratios of AUC_0-t and AUC_0-∞ (tablets vs capsules) were 1.00 (90% confidence interval [CI] 0.95-1.05) and 0.99 (90% CI 0.94-1.04), meeting BE criteria. Tablet C_max was modestly higher (geometric mean ratio 1.22, 90% CI 1.14-1.30), with no expected clinical impact based on established zanubrutinib exposure-response relationships. Both formulations were well tolerated, with no serious adverse events. In vitro testing showed tablets readily dispersed into a stable suspension suitable for nasogastric tube administration. Together, these results supported zanubrutinib tablets as a flexible alternative to capsules, with the potential to reduce pill burden (4 capsules vs 2 tablets) and improve long-term adherence.