Clinical Pharmacology in Drug Development最新文献_第6页

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-29

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IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-29

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Pharmacokinetics, Pharmacodynamics, and Safety of Single-Dose Luseogliflozin (TS-071) in Japanese Children and Adolescents With Type 2 Diabetes: A Multicenter, Open-Label, Parallel-Group Phase 1 Study 单剂量吕西格列净（TS-071）在日本2型糖尿病儿童和青少年中的药代动力学、药效学和安全性：一项多中心、开放标签、平行组的1期研究

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-24 DOI: 10.1002/cpdd.70065

Toru Kikuchi, Hidefumi Nakamura, Hideo Umeuchi, Iwao Kitajima, Tatsuhiko Urakami

{"title":"Pharmacokinetics, Pharmacodynamics, and Safety of Single-Dose Luseogliflozin (TS-071) in Japanese Children and Adolescents With Type 2 Diabetes: A Multicenter, Open-Label, Parallel-Group Phase 1 Study","authors":"Toru Kikuchi, Hidefumi Nakamura, Hideo Umeuchi, Iwao Kitajima, Tatsuhiko Urakami","doi":"10.1002/cpdd.70065","DOIUrl":"10.1002/cpdd.70065","url":null,"abstract":"This study aimed to evaluate the pharmacokinetics, pharmacodynamics, and safety of a single dose of luseogliflozin (TS-071), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, in Japanese children and adolescents with type 2 diabetes, with the goal of informing dose selection for future research. In this multicenter, open-label, parallel-group Phase 1 trial, patients aged 9-17 years received a single oral dose of luseogliflozin at 1.25, 2.5, or 5 mg. Pharmacokinetic and pharmacodynamic parameters were assessed and compared with existing adult data. In total, 19 patients completed the study. The mean age was 14.3 ± 1.9 years, and the mean body weight was 77.28 ± 25.32 kg. Plasma luseogliflozin concentrations increased in a dose-dependent manner. The maximum plasma concentration and the area under the curve were comparable to those observed in adults. Administration of luseogliflozin at all dose levels resulted in a substantial increase in urinary glucose excretion. No safety concerns emerged from the single-dose administration. Luseogliflozin demonstrated favorable pharmacokinetic, pharmacodynamic, and safety profiles in pediatric patients, consistent with adult findings. These results support the selection of 2.5- and 5-mg doses for a future Phase 3 pediatric study.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-24

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Effects of Cedirogant on the Pharmacokinetics of Sensitive Cytochrome P450 Probe Substrates Cedirogant对敏感细胞色素P450探针底物药代动力学的影响。

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-19 DOI: 10.1002/cpdd.70059

Ronilda D'Cunha, Yuli Qian, Shuai Hao, Jason Eccleston, Gweneth F. Levy, Shashikanth Gannu, David G. Rizzo, Wei Liu, Mohamed-Eslam F. Mohamed

{"title":"Effects of Cedirogant on the Pharmacokinetics of Sensitive Cytochrome P450 Probe Substrates","authors":"Ronilda D'Cunha, Yuli Qian, Shuai Hao, Jason Eccleston, Gweneth F. Levy, Shashikanth Gannu, David G. Rizzo, Wei Liu, Mohamed-Eslam F. Mohamed","doi":"10.1002/cpdd.70059","DOIUrl":"10.1002/cpdd.70059","url":null,"abstract":"This study aimed to characterize the effects of cedirogant, an inverse agonist of retinoic acid–related orphan receptor gamma thymus (RORγt), on activities of cytochrome P450 (CYP) enzymes in healthy adults. Twenty study participants received a single oral dose of the modified Cooperstown 5+1 cocktail CYP probe drugs alone without cedirogant (Period 1, midazolam on Day 1 and other CYP substrates on Day 2), and again following once-daily dosing of 375 mg cedirogant (Period 2, cedirogant on Days 1-18, midazolam on Day 13, and other CYP substrates on Day 14). Blood samples and 12-hour urine samples were collected to measure the exposures of the CYP probe drugs and selected metabolites. The point estimates (90% confidence intervals) of the area under the plasma concentration–time curve from time 0 to infinity (AUCinf) ratio with and without cedirogant co-administration were 0.370 (0.325-0.420) for midazolam (CYP3A), 1.161 (1.031-1.307) for caffeine (CYP1A2), and 0.788 (0.761-0.816) for S-Warfarin (CYP2C9). The estimated ratios of plasma metabolite/parent AUC ratio for omeprazole (CYP2C19) and parent/metabolite molar urine recovery ratio for dextromethorphan (CYP2D6) with versus without cedirogant co-administration were 2.115 (1.813-2.467) and 0.951 (0.802-1.128), respectively. Based on these findings, once-daily administration of 375-mg cedirogant showed moderate induction of CYP3A and CYP2C19, a weak effect on CYP2C9, and no clinically relevant effects on CYP1A2 or CYP2D6.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-19

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Bioequivalence and Safety Assessment of Brivaracetam Dry Syrup Compared With Tablets in Healthy Japanese Participants: Results From Two Randomized Single- and Multiple-Dose Trials 布瓦西坦干糖浆与片剂在日本健康受试者中的生物等效性和安全性评价：两项随机单剂量和多剂量试验的结果

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-17 DOI: 10.1002/cpdd.70057

Yoshinobu Hayakawa, Ryoji Yoshinaka, Tomonobu Sano, Walter Krauwinkel, Tadaharu Soma, Hiroshi Sasamoto, Jan-Peer Elshoff, Almasa Bass, Ying Chen, Nozomi Kurihara, Harumi Murakami

{"title":"Bioequivalence and Safety Assessment of Brivaracetam Dry Syrup Compared With Tablets in Healthy Japanese Participants: Results From Two Randomized Single- and Multiple-Dose Trials","authors":"Yoshinobu Hayakawa, Ryoji Yoshinaka, Tomonobu Sano, Walter Krauwinkel, Tadaharu Soma, Hiroshi Sasamoto, Jan-Peer Elshoff, Almasa Bass, Ying Chen, Nozomi Kurihara, Harumi Murakami","doi":"10.1002/cpdd.70057","DOIUrl":"10.1002/cpdd.70057","url":null,"abstract":"The antiseizure medication brivaracetam is available as tablets, oral solution, and solution for intravenous injection in many countries. A dry syrup formulation is being developed for use in Japan. We report two phase 1, single-center, open-label, randomized, two-way crossover trials that assessed bioequivalence, safety, and tolerability of brivaracetam dry syrup and tablet formulations in healthy adult male Japanese participants. EP0110 (NCT05315947) assessed brivaracetam 50 mg dry syrup versus tablet after a single administration (N = 24). Although pharmacokinetic profiles were similar and bioequivalence criteria for AUC were met, bioequivalence criteria for the observed Cmax were not met in this trial. A subsequent simulation of parameters at steady state, based on EP0110 data, indicated that bioequivalence could be established in a multiple-dose setting. EP0231 (NCT06312566) was designed employing a group sequential design (N = 96) and assessed brivaracetam 50 mg dry syrup versus tablet after multiple oral doses (N = 64). The point estimates (92.016% CIs) for Cmax and AUC at steady state fell within the acceptable range for bioequivalence (0.80-1.25). Bioequivalence of dry syrup and tablet formulations was demonstrated after multiple doses. Single and multiple doses of brivaracetam 50 mg administered as dry syrup or tablet formulation were generally safe and well tolerated in healthy Japanese participants.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-17

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IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-10

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Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Voriconazole Tablets in Healthy Chinese Volunteers 两种伏立康唑片在中国健康志愿者体内的药代动力学、生物等效性和安全性评价。

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2026-04-10 DOI: 10.1002/cpdd.70058

Pan Luo, Yongfang Lei, Chang Liu, Juan Du, Xiangxiao Deng, Hengyi Yu, Xingxing Qi, Zheng He, Dongling Zhang, Qin Zuo, Yinian Fang, Dong Liu, Qian Chen, Xiuhua Ren

{"title":"Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Voriconazole Tablets in Healthy Chinese Volunteers","authors":"Pan Luo, Yongfang Lei, Chang Liu, Juan Du, Xiangxiao Deng, Hengyi Yu, Xingxing Qi, Zheng He, Dongling Zhang, Qin Zuo, Yinian Fang, Dong Liu, Qian Chen, Xiuhua Ren","doi":"10.1002/cpdd.70058","DOIUrl":"10.1002/cpdd.70058","url":null,"abstract":"Voriconazole is a broad-spectrum antifungal agent belonging to the triazole class, exhibiting significant efficacy against a diverse array of pathogenic organisms. This study aimed to assess the pharmacokinetic properties, bioequivalence, and safety profiles of two oral formulations of voriconazole tablets. An open-label, randomized, two-period, two-sequence crossover, Phase I bioequivalence trial was conducted involving healthy Chinese volunteers under fasting conditions. During each study period, participants were administered a single 200 mg dose of either the generic (test) or branded (reference) voriconazole tablet, with treatment sequences assigned randomly. Blood samples were collected at various time points before and after administration to determine plasma voriconazole concentrations. The study assessed bioequivalence by calculating the maximum concentration (Cmax) and the area under the concentration–time curve (AUC). Adverse events (AEs) were systematically documented. A total of seventy healthy volunteers were recruited, with 68 participants who received voriconazole included in the final analysis. The geometric mean ratios (GMR) of the test tablet to the reference for Cmax, the area under the concentration curve from time 0 to the last measurable time point (AUC0–t), and the area under the concentration curve from time 0 extrapolated to infinity (AUC0–inf) were determined to be 1.03, 0.98, and 0.97, respectively, under fasting conditions. These values met the established criteria for bioequivalence acceptance. Furthermore, both the test and reference formulations of voriconazole were well tolerated. The findings indicate that the test and reference voriconazole tablets are bioequivalent and possess similar safety profiles in healthy Chinese volunteers.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644421","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}

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