Clinical Pharmacology in Drug Development最新文献

A Randomized Thorough QT Trial Using Concentration-QT Analysis to Evaluate the Effects of Centanafadine on Cardiac Repolarization. 一项随机、全面的QT试验，使用浓度-QT分析来评估Centanafadine对心脏复极的影响。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-27 DOI: 10.1002/cpdd.1545

Osman S Turkoglu, Xiaofeng Wang, Jennifer Repella-Gordon, Susan E Shoaf

{"title":"A Randomized Thorough QT Trial Using Concentration-QT Analysis to Evaluate the Effects of Centanafadine on Cardiac Repolarization.","authors":"Osman S Turkoglu, Xiaofeng Wang, Jennifer Repella-Gordon, Susan E Shoaf","doi":"10.1002/cpdd.1545","DOIUrl":"https://doi.org/10.1002/cpdd.1545","url":null,"abstract":"Centanafadine is a norepinephrine/dopamine/serotonin reuptake inhibitor in development for treatment of attention-deficit/hyperactivity disorder. This double-blind, placebo- and moxifloxacin-controlled, 3-period crossover trial evaluated the effects of centanafadine (EB-1020) and its metabolite (EB-10601) on cardiac repolarization in 30 healthy adults (18-65 years). Dosing sequences included centanafadine sustained-release 800 mg (supratherapeutic) total daily dose, placebo, and moxifloxacin 400 mg. Electrocardiogram parameters and heart rate (HR) were assessed. The primary endpoint was placebo-corrected change from baseline QTc (ΔΔQTc), analyzed using concentration-QTc (C-QTc) analysis. The C-QTc slopes for centanafadine (-0.001 ms/[ng/mL]) and EB-10601 (-0.0003 ms/[ng/mL]) were not statistically significant. Assay sensitivity was confirmed by the statistically significant C-QTc slope for moxifloxacin (0.004 ms/[ng/mL]) and a 2-sided 90% confidence interval lower bound >5 milliseconds. No change from baseline in QTcF or placebo-corrected QTcF ≥10 milliseconds for centanafadine was observed at any postdose time point. No centanafadine-treated participants had QTcF increases of >30 milliseconds and no relevant PR/QRS interval or HR increases were observed. The predicted ΔΔQTcF values of centanafadine, EB-10601, and moxifloxacin at the geometric mean Cmax were -2.72, -1.59, and 11.75 milliseconds, respectively. No serious treatment-emergent adverse events or deaths were reported. Centanafadine was generally safe and well-tolerated, with no clinically meaningful effect on cardiac repolarization.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combined Immediate-Release and Extended-Release Formulation of Sodium Valproate Provides Stable Plasma Levels for Inhibition of Histone Deacetylation. 丙戊酸钠速释和缓释联合制剂提供稳定的血浆水平来抑制组蛋白去乙酰化。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-27 DOI: 10.1002/cpdd.1555

Nikhil Ahuja, Susanna Kääriäinen, Zsófia Lovró, Mia Lundblad, Kristina Drott, Elsa Lilienberg, Marica T Engström, Karla Saukkonen, Mika Scheinin

{"title":"Combined Immediate-Release and Extended-Release Formulation of Sodium Valproate Provides Stable Plasma Levels for Inhibition of Histone Deacetylation.","authors":"Nikhil Ahuja, Susanna Kääriäinen, Zsófia Lovró, Mia Lundblad, Kristina Drott, Elsa Lilienberg, Marica T Engström, Karla Saukkonen, Mika Scheinin","doi":"10.1002/cpdd.1555","DOIUrl":"https://doi.org/10.1002/cpdd.1555","url":null,"abstract":"A modified controlled-release sodium valproate formulation (VAL001, test) was compared with an approved enteric-coated tablet formulation (Absenor, reference). Pharmacokinetics and safety/tolerability were evaluated in healthy subjects to bridge with positive efficacy results from an early-phase patient trial of valproate in combination with chemotherapy in diffuse large B-cell lymphoma. In Part I (n = 12), both formulations were administered as single doses (30 mg/kg) in a randomized crossover fashion. Equivalent exposures (area under the plasma concentration-time curve) for total and free valproate were observed under fasted conditions. Intake with food delayed the absorption of valproate from the test formulation, with no impact on AUC. In Part II (n = 27), both formulations were administered over 3 consecutive days, at 30 mg/kg twice daily (test) or 20 mg/kg 3 times daily (reference). Similar steady-state levels were observed, but fluctuation was less with the test product (23% vs. 47%, P = .0102). Inhibition of histone deacetylase activity was evidenced by increased levels of acetylated H3K9 in peripheral blood mononuclear cells. No serious or severe adverse events were observed. The novel capsule formulation of valproate, containing a combination of immediate-release granules and extended-release pellets, appears to have suitable pharmacokinetic properties for cancer treatments aiming for histone deacetylase inhibition.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics, Safety, and Tolerability of Single-Dose Dazukibart in Healthy Adults in China and Japan: Results From 2 Randomized, Double-Blind, Phase 1 Studies. 中国和日本健康成人单剂量大佐吉bart的药代动力学、安全性和耐受性：来自2项随机、双盲、1期研究的结果

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-22 DOI: 10.1002/cpdd.1522

Naihan Chen, Yamato Sano, Xiaohong Wang, Shuiyi Hu, Junichi Tabira, Xin Luo, Hiroki Yoshimatsu, John Prybylski, Myron Chu, Haiyan Li, Kenji Takazawa

{"title":"Pharmacokinetics, Safety, and Tolerability of Single-Dose Dazukibart in Healthy Adults in China and Japan: Results From 2 Randomized, Double-Blind, Phase 1 Studies.","authors":"Naihan Chen, Yamato Sano, Xiaohong Wang, Shuiyi Hu, Junichi Tabira, Xin Luo, Hiroki Yoshimatsu, John Prybylski, Myron Chu, Haiyan Li, Kenji Takazawa","doi":"10.1002/cpdd.1522","DOIUrl":"https://doi.org/10.1002/cpdd.1522","url":null,"abstract":"Dazukibart is a humanized monoclonal antibody selectively targeting interferon-β. The pharmacokinetics (PK), safety, tolerability, and immunogenicity of dazukibart were evaluated in 2 double-blind, randomized, placebo-controlled, single-dose, Phase 1 studies in healthy adults in China (Study 1: N = 18; dazukibart 900 mg = 15; placebo = 3) and Japan (Study 2: N = 12; Cohort 1: dazukibart 300 mg = 5, placebo = 1; and Cohort 2: dazukibart 900 mg = 5, placebo = 1). PK parameters were assessed after dosing in Study 1 and Study 2, and no significant differences were observed between PK findings among participants in both studies. A biphasic decline in dazukibart serum concentrations was observed in both studies. Exposures increased dose proportionally in Study 2. Body weight, but not race, was identified as an independent covariate of exposure using population PK modeling (including data from a Phase 1 US study [NCT02766621]). No deaths/discontinuations or serious/severe adverse events were observed, mostly mild adverse events were reported. No participants in Study 1 were antidrug antibody positive; 20.0% in Study 2 were positive for treatment-induced antidrug antibodies and neutralizing antibodies. PK parameters and immunogenicity rates were consistent with the US study, and no new safety signals were identified.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics and Safety Study of HN0141, a Novel Anti-Human Cytomegalovirus Inhibitor, in Healthy Volunteers. 新型抗人巨细胞病毒抑制剂HN0141在健康志愿者体内的药动学及安全性研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-16 DOI: 10.1002/cpdd.1542

George Hill, Hong Gao, Yingzhe Fan, Rui Zhang, Lu Wang, Zhaoshan Zong, Yi Zhou, Donghui Qin, Jie Hou

{"title":"Pharmacokinetics and Safety Study of HN0141, a Novel Anti-Human Cytomegalovirus Inhibitor, in Healthy Volunteers.","authors":"George Hill, Hong Gao, Yingzhe Fan, Rui Zhang, Lu Wang, Zhaoshan Zong, Yi Zhou, Donghui Qin, Jie Hou","doi":"10.1002/cpdd.1542","DOIUrl":"https://doi.org/10.1002/cpdd.1542","url":null,"abstract":"HN0141 is a human cytomegalovirus (HCMV) DNA terminase complex inhibitor being developed for prophylaxis and/or preemptive treatment of HCMV infection and diseases. This study evaluated the safety, tolerability, and pharmacokinetics (PK) of HN0141, following oral administration in healthy volunteers. The double-blind, placebo-controlled Phase 1 study comprised Part 1, an escalating, single-dose study involving 50-, 100-, 200-, 300-, 400-, and 525-mg doses; and Part 2, a multiple-dose study over 7 days involving 50-, 100-, 200-, and 400-mg twice-daily doses. HN0141 was rapidly absorbed following oral doses, with median time to maximum concentration achieved within 1-2 hours across all doses. At doses ranging from 50 to 100 mg, the PK profile was reasonably linear, while at doses above 200 mg, the PK profile was more than proportional. The predicted therapeutic dose would be 50-200 mg twice daily, which is at a reasonable linear PK range. All exposures tested (up to 525-mg single dose and 400-mg twice-daily multiple doses) were within the no-observed-adverse-effect level defined in animal toxicity studies. There was a mild accumulation on systemic exposure at steady state, which was achieved within 72 hours of multiple twice-daily dosing. No serious or severe adverse events were reported. HN0141's PK profile favors the twice-daily dosing, which gives a smaller concentration variation during the treatment, and thus could bring a better treatment effect with sufficient convenience. These Phase 1 data in safety and PK profile warrant further drug development in both preemptive and prophylactic treatment in patients with HCMV.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety, Tolerability, and Pharmacokinetics of Donanemab in Healthy Chinese Participants: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study. Donanemab在中国健康受试者中的安全性、耐受性和药代动力学：一项随机、双盲、安慰剂对照的1期研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-16 DOI: 10.1002/cpdd.1533

Junyu Xu, Nan Zhao, Yihui Wang, Ivelina Gueorguieva, Chenxi Qian, Yimin Cui

{"title":"Safety, Tolerability, and Pharmacokinetics of Donanemab in Healthy Chinese Participants: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study.","authors":"Junyu Xu, Nan Zhao, Yihui Wang, Ivelina Gueorguieva, Chenxi Qian, Yimin Cui","doi":"10.1002/cpdd.1533","DOIUrl":"https://doi.org/10.1002/cpdd.1533","url":null,"abstract":"Alzheimer's disease (AD), characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles, is the leading cause of dementia globally. Donanemab is a humanized immunoglobulin G1 in development as a treatment to slow AD progression. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PKs), and immunogenicity of donanemab in healthy Chinese adults. The study included screening, inpatient, and follow-up periods. Following successful screening, participants were assigned to one of three donanemab cohorts (350, 700, or 1400 mg) and randomized in a 5:1 ratio to receive donanemab or placebo. Participants received a single intravenous (IV) dose of donanemab or placebo, and the safety, PKs, and immunogenicity of donanemab were monitored. A total of 36 male Chinese participants were included. All treatment-emergent adverse events (TEAEs) were mild in severity. Two participants on 350 mg donanemab experienced treatment-related TEAEs. Serum concentrations decreased over time with dose-dependent PK parameters (Cmax, t1/2, AUC0-tlast, and AUC0-inf) as expected. Clearance values were similar across doses. All donanemab recipients developed treatment-emergent antidrug antibodies (ADAs) in the inpatient and follow-up periods, with similar ADA titer ranges across all donanemab doses. Single IV doses of donanemab 350, 700, and 1400 mg showed acceptable safety, tolerability, and dose-proportional PK in healthy Chinese adults.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of Potential Effects of CYP3A Inhibition and CYP3A Induction on the Pharmacokinetics of Fruquintinib in Healthy Subjects. 抑制和诱导CYP3A对fruquininib在健康人体内药代动力学的潜在影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-14 DOI: 10.1002/cpdd.1520

Martha Gonzalez, Zhao Yang, William R Schelman, Xiaofei Zhou, Neeraj Gupta, Caly Chien

{"title":"Evaluation of Potential Effects of CYP3A Inhibition and CYP3A Induction on the Pharmacokinetics of Fruquintinib in Healthy Subjects.","authors":"Martha Gonzalez, Zhao Yang, William R Schelman, Xiaofei Zhou, Neeraj Gupta, Caly Chien","doi":"10.1002/cpdd.1520","DOIUrl":"https://doi.org/10.1002/cpdd.1520","url":null,"abstract":"Cytochrome P450 (CYP) 3A plays a significant role in fruquintinib metabolism in vitro. This 2-part, 2-period fixed-sequence study investigated the impact of CYP3A inhibition (itraconazole) and CYP3A induction (rifampin) on the pharmacokinetics (PK) of fruquintinib and M11, its main metabolite. Fourteen healthy subjects in each part received a single dose of fruquintinib 5 mg alone in Period 1 and with itraconazole (Part A) or rifampin (Part B) in Period 2 under fasted conditions. Itraconazole or rifampin was administered daily 4 or 7 days before coadministration, respectively; administration of both continued throughout the PK sampling period. PK samples were collected before dosing and over 168 hours after fruquintinib dosing. Coadministration with itraconazole resulted in an increase of fruquintinib systemic exposure, determined by area under the plasma concentration-time curves (AUCs) by approximately 10%. Decreases in M11 AUCs and maximum plasma concentration (Cmax) ranged from 44% to 55% but were not considered clinically meaningful. Rifampin reduced fruquintinib Cmax and AUCs by 12% and 65%, respectively. Rifampin had a marginal effect on M11 AUCs and increased M11 Cmax by 2.3-fold. Data support that concomitant use of fruquintinib with potent CYP3A inducers of rifampin-like potency should be avoided, but no dose adjustment is recommended when coadministered with CYP3A inhibitors.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics and Safety Evaluation of a New Generic Sitafloxacin: A Phase I Bioequivalence Study in Healthy Chinese Participants. 新仿制药西他沙星的药代动力学和安全性评价：中国健康受试者的I期生物等效性研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-14 DOI: 10.1002/cpdd.1519

Yongfang Lei, Pan Luo, Yuzhu Chen, Liuliang Xue, Donglin Zhang, Xingxing Qi, Yinian Fang, Hengyi Yu, Zheng He, Qin Zuo, Chang Liu, Dong Liu, Xinhua Ren, Qian Chen

{"title":"Pharmacokinetics and Safety Evaluation of a New Generic Sitafloxacin: A Phase I Bioequivalence Study in Healthy Chinese Participants.","authors":"Yongfang Lei, Pan Luo, Yuzhu Chen, Liuliang Xue, Donglin Zhang, Xingxing Qi, Yinian Fang, Hengyi Yu, Zheng He, Qin Zuo, Chang Liu, Dong Liu, Xinhua Ren, Qian Chen","doi":"10.1002/cpdd.1519","DOIUrl":"https://doi.org/10.1002/cpdd.1519","url":null,"abstract":"Sitafloxacin is a new antibiotic drug belonging to the fourth generation quinolone antibiotics. The aim of this study was to evaluate the pharmacokinetics (PK), safety profiles, and bioequivalence of test and reference 50-mg sitafloxacin tablets under fasting and fed conditions. The PK parameters, which were calculated with noncompartmental model, including maximum concentration, area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity. The bioequivalence was assessed on the basis of whether the 90% confidence intervals of the geometric mean ratio for the test/reference drugs fell within the accepted range of 80%-125%. Adverse events were monitored to assess safety. Finally, 80 healthy Chinese participants were enrolled, of which 40 were enrolled in the fasting study and the other 40 enrolled in the fed study. There was 1 participant in the fed trial who withdrew from the study because of failure to finish the high-fat meal. The geometric mean ratio and its 90% confidence interval for the maximum concentration, AUC from time 0 to the last quantifiable concentration, AUC from time 0 to infinity between the branded and generic sitafloxacin, under both fasting and fed conditions, were compliant with the predefined bioequivalence criteria of 80%-125%. No serious adverse events were observed in this study. Therefore, the findings indicate that generic and original sitafloxacin tablets have comparable bioequivalence and safety profiles.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Mild to Moderate Hepatic Impairment on Valemetostat Pharmacokinetics: An Open-Label, Phase I Study. 轻度至中度肝功能损害对缬美托他药代动力学的影响：一项开放标签I期研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-14 DOI: 10.1002/cpdd.1544

Masaya Tachibana, Thuy Vu Craveiro, Thomas C Marbury, Samuel Oberstein, George J Atiee, Ben Tao, Takako Shimizu, Yvonne Lau, Malaz A Abutarif

{"title":"Effect of Mild to Moderate Hepatic Impairment on Valemetostat Pharmacokinetics: An Open-Label, Phase I Study.","authors":"Masaya Tachibana, Thuy Vu Craveiro, Thomas C Marbury, Samuel Oberstein, George J Atiee, Ben Tao, Takako Shimizu, Yvonne Lau, Malaz A Abutarif","doi":"10.1002/cpdd.1544","DOIUrl":"https://doi.org/10.1002/cpdd.1544","url":null,"abstract":"Valemetostat tosylate (valemetostat) is a dual inhibitor of enhancer of zeste homolog (EZH) 2 and EZH1, approved in Japan for the treatment of relapsed/refractory peripheral T-cell lymphoma and adult T-cell leukemia/lymphoma. This Phase I, open-label study evaluated the pharmacokinetics and safety of a single 50-mg oral dose of valemetostat in participants with hepatic impairment (HI). In total, 24 participants were enrolled into 3 cohorts of mild HI (n = 8) and moderate HI (n = 8) according to the National Cancer Institute's Organ Dysfunction Working Group criteria, and matched healthy participants with normal hepatic function (HF; n = 8). In participants with mild and moderate HI, total valemetostat (bound + unbound) area under the concentration-time curve extrapolated to infinity was 23% lower (geometric mean ratio [GMR], 77.2% [90% confidence interval (CI), 44.0-135]) and 35% lower, (GMR, 64.8% [90% CI, 40.6-103]), respectively, and unbound valemetostat was 19% lower (GMR, 81.1% [90% CI, 47.4-139]) and 15% higher (GMR, 115% [90% CI, 75.5-176]), than in participants with normal HF. No treatment-related adverse events were reported. Based on the result of this trial, no dosing adjustments are recommended for patients with mild to moderate HI receiving valemetostat.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetic and Bioequivalence Evaluation of Prolonged-Release Octreotide Acetate Microspheres in Healthy Human Subjects. 缓释醋酸奥曲肽微球在健康人体内的药动学及生物等效性评价。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-12 DOI: 10.1002/cpdd.1521

Chenjing Wang, Xin Li, Xingli Gu, Haixun Hu, Zhaoguo Lv, Yanhua Sun, Yanzhi Li, Chenxi Hao, Yanping Liu, Yao Fu, Qingmin Yang, Yu Cao

{"title":"Pharmacokinetic and Bioequivalence Evaluation of Prolonged-Release Octreotide Acetate Microspheres in Healthy Human Subjects.","authors":"Chenjing Wang, Xin Li, Xingli Gu, Haixun Hu, Zhaoguo Lv, Yanhua Sun, Yanzhi Li, Chenxi Hao, Yanping Liu, Yao Fu, Qingmin Yang, Yu Cao","doi":"10.1002/cpdd.1521","DOIUrl":"https://doi.org/10.1002/cpdd.1521","url":null,"abstract":"Somatostatin analogs such as octreotide have been used in the treatment of acromegaly in the past decades, due to their efficacy in relieving symptoms and lowering growth hormone and insulin-like growth factor 1 levels. Herein, the pharmacokinetic (PK) profile and safety of generic (test product) octreotide acetate microspheres and brand name (reference product) octreotide acetate microspheres in healthy volunteers were compared to assess the bioequivalence. Healthy volunteers were randomized 1:1 to receive single doses of the test product and reference product, respectively. Blood samples of each patient were collected at specific time intervals over an 82-day period. Plasma drug concentrations were tested. The PK parameters were analyzed and compared. Analysis of variance on log-transformed primary PK parameters was applied to analyze the bioequivalence between the test and reference product. The bioequivalence margin was 80%-125%. The PK parameters between the 2 groups were numerically similar. All 90% confidence intervals of the geometric mean ratio for the primary PK parameters fell within 80%-125%, confirming the bioequivalence of the 2 drugs. In this study, 172 (73.9%) adverse events, including 1 (0.4%) non-treatment-related serious adverse event in the test group, were reported. The test product is bioequivalent to the reference product with acceptable safety. The octreotide acetate microspheres provided by 2 sponsors are alternative products.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A 2-Part, Open-Label, Phase 1 Bioequivalence and Food-Effect Study of Ubrogepant in Healthy Adult Participants. 一项2部分、开放标签、i期研究：ubrogeagent在健康成人中的生物等效性和食物效应。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-05-10 DOI: 10.1002/cpdd.1546

Ramesh Boinpally, Joel M Trugman

{"title":"A 2-Part, Open-Label, Phase 1 Bioequivalence and Food-Effect Study of Ubrogepant in Healthy Adult Participants.","authors":"Ramesh Boinpally, Joel M Trugman","doi":"10.1002/cpdd.1546","DOIUrl":"https://doi.org/10.1002/cpdd.1546","url":null,"abstract":"This Phase 1 study of ubrogepant was conducted to establish the bioequivalence (BE) of the 50- and 100-mg to-be-marketed (TBM) tablet formulations with the clinical trial (CT) 100-mg tablet formulation and evaluate the food effect on the bioavailability of the 100-mg TBM tablet. This 2-part study enrolled healthy participants aged 18-45 years. Part A assessed BE following a single dose of TBM versus CT tablets. Part B evaluated the impact of a high-fat meal on ubrogepant pharmacokinetics. Safety and tolerability were assessed along with standard pharmacokinetic parameters. In Part A (n = 47), the geometric mean ratio and 90% confidence intervals for maximum plasma drug concentration, area under the plasma concentration-time curve (AUC) from time zero to time t, and AUC from time zero to infinity for the TBM and CT formulations demonstrated BE. The time to peak exposure was the same for both formulations. In Part B (n = 18), a high-fat meal delayed time to peak exposure and reduced maximum plasma drug concentration by 22%, with no effect on AUC. The occurrence of treatment-emergent adverse events was low, and the majority were mild. Ubrogepant TBM and CT tablets (1 × 100 mg or 2 × 50 mg) were bioequivalent under fasted conditions, and a high-fat meal had no clinically relevant effect on the bioavailability of the TBM tablet formulation.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0