Clinical Pharmacology in Drug Development最新文献

Population Pharmacokinetics of Butylphthalide Injection in Elderly Chinese Patients With Ischemic Stroke.

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-03-28 DOI: 10.1002/cpdd.1525

Shu-Xian Lyu, Xue-Yan Cui, Shi-Xian Chen, Hai-Yan Shi, Xin Huang

{"title":"Population Pharmacokinetics of Butylphthalide Injection in Elderly Chinese Patients With Ischemic Stroke.","authors":"Shu-Xian Lyu, Xue-Yan Cui, Shi-Xian Chen, Hai-Yan Shi, Xin Huang","doi":"10.1002/cpdd.1525","DOIUrl":"https://doi.org/10.1002/cpdd.1525","url":null,"abstract":"Butylphthalide is widely used to treat acute ischemic stroke in China, and the main adverse effect is the increase in transaminase levels. We aimed to establish a population pharmacokinetic model of butylphthalide in elderly patients with ischemic stroke and identified covariates influencing butylphthalide pharmacokinetics. We collected butylphthalide blood samples via opportunistic sampling. We chose the base model, compared 1-, 2-, and 3-compartment models, and used basic patient information, laboratory test results, concomitant drugs, and comorbidities as covariates to examine our study. Our study included 50 patients (n = 106 blood samples), and a 2-compartment model with first-order elimination matched the experimental data well. Body weight and comorbid diabetes significantly affect the clearance of butylphthalide. On the basis of the final PPK model, the Monte Carlo method was used to compare the effects of different body weights and the state of diabetes on the steady-state area under the concentration-time curve at 0-24 hours. The results revealed that the steady-state area under the concentration-time curve at 0-24 hours was lower in patients with diabetes than in patients without diabetes, and both values decreased with weight gain. Our findings provide information for personalized treatment plans for patients with ischemic stroke (aged 65 years or older) receiving butylphthalide injection.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735958","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

Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P-Glycoprotein Inhibition.

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-03-27 DOI: 10.1002/cpdd.1526

Hongxia Jia, T Eric Ballard, Liming Zhang, Lawrence Cohen, Mackenzie C Bergagnini-Kolev, Ian E Templeton, Hannah M Jones, Wei Yin

{"title":"Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P-Glycoprotein Inhibition.","authors":"Hongxia Jia, T Eric Ballard, Liming Zhang, Lawrence Cohen, Mackenzie C Bergagnini-Kolev, Ian E Templeton, Hannah M Jones, Wei Yin","doi":"10.1002/cpdd.1526","DOIUrl":"https://doi.org/10.1002/cpdd.1526","url":null,"abstract":"Soticlestat (TAK-935) is a cholesterol 24-hydroxylase inhibitor. A physiologically-based pharmacokinetic model has been developed to predict potential soticlestat drug-drug interactions (DDIs) using the Simcyp v20 Population-based Simulator and verified with data from single-/multiple-rising-dose and clinical DDI studies. Simulated area under the plasma concentration-time curve from 0 to infinity (AUC0-inf) and maximal drug concentration (Cmax) based on the model were generally within 2-fold of observed values for all soticlestat doses. Model-simulated versus observed AUC0-inf and Cmax geometric mean ratios (GMRs) for soticlestat with/without itraconazole (potent cytochrome P450 [CYP] 3A inhibitor), and mefenamic acid (potent UDP glucuronosyltransferase [UGT] 1A9 inhibitor) were ≤1.10-fold. As soticlestat is primarily metabolized by UGT enzymes and Simulator v20 incorporates rifampin's induction of CYP3A only, the model underpredicted soticlestat's DDI with rifampin. However, with user-defined rifampin UGT induction, the predicted AUC0-inf GMR was within 1.5-fold of the observed value, meeting the 2-fold acceptance criteria. Hence, the model was appropriate for evaluating DDIs with CYP3A inhibitors and inducers not evaluated in clinical DDI studies; all predicted DDIs were low/not clinically relevant (<50% impact on exposure). Furthermore, no clinically significant DDIs were predicted following coadministration of soticlestat with sensitive CYP2C8, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein substrates.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718270","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

Target-Mediated Modeling of Alirocumab in Adolescents and Children ≥8 to <12 Years of Age Using Phase II and III Data.

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-03-26 DOI: 10.1002/cpdd.1523

Pavel Kovalenko, Lutz Harnisch, Jeanne Mendell, Yuhuan Wang, John D Davis, Albert Thomas DiCioccio

{"title":"Target-Mediated Modeling of Alirocumab in Adolescents and Children ≥8 to <12 Years of Age Using Phase II and III Data.","authors":"Pavel Kovalenko, Lutz Harnisch, Jeanne Mendell, Yuhuan Wang, John D Davis, Albert Thomas DiCioccio","doi":"10.1002/cpdd.1523","DOIUrl":"https://doi.org/10.1002/cpdd.1523","url":null,"abstract":"A population pharmacokinetic (PK) covariate analysis was conducted utilizing data from adolescents and children ≥8 to <12 years of age with heterozygous familial hypercholesterolemia. One phase II and 1 phase III study were analyzed (121 patients on active treatment). A 2-compartment target-mediated model with linear and target-mediated elimination and transit compartments describing lag time in absorption was utilized. Weight and high-dose statins were statistically significant covariate. Except for the central volume, estimated population PK parameters describing linear kinetics were similar across pediatric patients and healthy adults. Coadministration of concomitant high doses of statins was associated with an increase in the production rate of proprotein convertase subtilisin/kexin type 9. The primary covariate model adequately described alirocumab PKs in the pediatric population. The analysis supports the recommended weight-adjusted subcutaneous dosing regimens for alirocumab in children with heterozygous hypercholesterolemia aged ≥8 years.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708817","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

CPDD 2024 Reviewer List

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-03-04 DOI: 10.1002/cpdd.1524

引用次数: 0

Lack of Pharmacokinetic Drug–Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-02-14 DOI: 10.1002/cpdd.1518

Kelong Han, Amir S. Youssef, Mindy Magee, Steve Hood, Helen Tracey, Jesse Kwoh, Dickens Theodore, Melanie Paff, Ahmed Nader

{"title":"Lack of Pharmacokinetic Drug–Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs","authors":"Kelong Han, Amir S. Youssef, Mindy Magee, Steve Hood, Helen Tracey, Jesse Kwoh, Dickens Theodore, Melanie Paff, Ahmed Nader","doi":"10.1002/cpdd.1518","DOIUrl":"10.1002/cpdd.1518","url":null,"abstract":"Bepirovirsen is an antisense oligonucleotide currently in Phase 3 development to treat chronic hepatitis B virus (HBV) infection. Given the importance of coadministration of bepirovirsen and standard-of-care nucleos(t)ide analogs (NAs), we evaluated drug–drug interactions (DDIs) between bepirovirsen, entecavir (ETV), and tenofovir (TFV) using in vitro and clinical data obtained through innovative study design and sampling strategy. Static models employing in vitro data indicated that bepirovirsen is not a direct inhibitor or inducer of most drug-metabolizing enzymes or an inhibitor or substrate of drug transporters and poses no clinical DDI risk against NAs. Bepirovirsen plasma pharmacokinetic parameters and concentration–time profiles in patients with chronic HBV in the CS3 study (NCT02981602) were similar with or without ETV or TFV coadministration, indicating no effect of NA coadministration on bepirovirsen pharmacokinetics. In patients with chronic HBV receiving both bepirovirsen and ETV or TFV in the B-Clear study (NCT04449029), NA plasma concentrations and pharmacokinetic parameters were similar to those published without bepirovirsen coadministration, suggesting no effect of bepirovirsen coadministration on NA pharmacokinetics. This analysis demonstrated no DDI potential between bepirovirsen and NAs, suggesting that dedicated clinical DDI studies are not required. Bepirovirsen is currently being evaluated in Phase 3 studies in combination with NA.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 4","pages":"281-291"},"PeriodicalIF":1.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413625","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}

引用次数: 0

Bioavailability, Metabolism, and Excretion of [14C]-Tazemetostat in Patients With B-Cell Lymphomas or Advanced Solid Tumors

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-02-03 DOI: 10.1002/cpdd.1508

Yingxue Chen, Renli Teng, Julien Ogier

{"title":"Bioavailability, Metabolism, and Excretion of [14C]-Tazemetostat in Patients With B-Cell Lymphomas or Advanced Solid Tumors","authors":"Yingxue Chen, Renli Teng, Julien Ogier","doi":"10.1002/cpdd.1508","DOIUrl":"10.1002/cpdd.1508","url":null,"abstract":"This open-label, multicenter study (NCT03010982) evaluated the absolute bioavailability, characterized the disposition and metabolism, and investigated the metabolic profile of tazemetostat, a US Food and Drug Administration–approved inhibitor of enhancer of zeste homolog 2, following intravenous and oral [14C]-labeled and unlabeled tazemetostat in patients with B-cell lymphomas or advanced solid tumors. Patients received oral tazemetostat 800 mg twice daily for 14 days. On Day 15, patients received tazemetostat 800-mg tablets in a fasted state followed by an intravenous microdose of 12 µg [14C]-tazemetostat. On Day 16, patients received a [14C]-tazemetostat 800-mg solution with a meal, then continued tazemetostat 800 mg twice daily. Blood, plasma, urine, and fecal samples were collected for pharmacokinetic analyses, and recovery and excretion of the radioactivity of [14C]-labeled/unlabeled tazemetostat and its metabolites. The median absolute bioavailability was 31.8% (range, 20.2%-49.8%). Notable plasma components were EPZ-6930, unchanged tazemetostat, EPZ006931, and EPZ034163, accounting for 31.8%, 22.4%, 11.0%, and 3.5% of total drug-related exposure, respectively. Recovery of radiolabeled material ranged from 93.2% to 94.7%, with most excreted doses recovered within 48 hours in urine and by 96 hours in feces. Fecal elimination represented the principal route of elimination with a mean of 78.9% of the administered radioactive dose and renal excretion accounted for 15.4%.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"231-239"},"PeriodicalIF":1.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122239","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}

引用次数: 0

Multiple-Dose Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Subcutaneous Rusfertide, a Hepcidin Mimetic, in Healthy Subjects

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-29 DOI: 10.1002/cpdd.1514

Nishit B. Modi, Phillip Dinh, Ifode Ajari

{"title":"Multiple-Dose Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Subcutaneous Rusfertide, a Hepcidin Mimetic, in Healthy Subjects","authors":"Nishit B. Modi, Phillip Dinh, Ifode Ajari","doi":"10.1002/cpdd.1514","DOIUrl":"10.1002/cpdd.1514","url":null,"abstract":"Rusfertide, a peptide hepcidin mimetic, has shown efficacy in polycythemia vera. This trial investigated the multiple-dose pharmacokinetics, pharmacodynamics, and safety of once-weekly rusfertide 60 mg for 5 weeks in healthy subjects. Subjects were randomized to subcutaneous injection in the abdomen, upper arm, or thigh. Eighteen subjects were enrolled, and 15 completed the study. Geometric mean peak rusfertide plasma concentrations (Cmax) following the first dose were 547, 387, and 560 ng/mL following injection in the abdomen, thigh, and arm, respectively (P = .0054). There was no difference between injection sites in the rusfertide area under the plasma concentration-time curve (AUC) following the first dose (P ≥ .179) or in the Cmax or AUC during the dosing interval following the last dose (P ≥ .238). Geometric mean accumulation (Dose 5/Dose 1) for AUC and Cmax was 1.5 and 1.2, respectively, and similar across injection sites. Mechanism-based decreases in serum iron, transferrin-iron saturation, hemoglobin, and hematocrit were noted following multiple doses. There were no differences between injection sites in the pharmacodynamic effect as measured by change from baseline in hematocrit values. There were no serious adverse events. Treatment-emergent adverse events in 2 or more subjects were injection-site reactions (erythema, induration, pruritus), fatigue, and headache. There were no clinically relevant findings in the safety laboratory parameters, vital signs, electrocardiograms, or physical examination. While a higher incidence of treatment-emergent adverse events was noted in these healthy participants following multiple doses of 60 mg, rusfertide was generally well tolerated. There were no clinically meaningful differences in rusfertide pharmacokinetics or pharmacodynamics between injection sites.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 4","pages":"311-323"},"PeriodicalIF":1.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064248","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}

引用次数: 0

Pharmacokinetics of Depemokimab Delivered by Safety Syringe Device or Autoinjector in Healthy Adults: A Phase 1, Single-Dose Study

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-28 DOI: 10.1002/cpdd.1506

Stein Schalkwijk, Chiara Zecchin, Anusmita Sen, Sei Choi, Kai Wang, Jeff Min, Brian Spears

{"title":"Pharmacokinetics of Depemokimab Delivered by Safety Syringe Device or Autoinjector in Healthy Adults: A Phase 1, Single-Dose Study","authors":"Stein Schalkwijk, Chiara Zecchin, Anusmita Sen, Sei Choi, Kai Wang, Jeff Min, Brian Spears","doi":"10.1002/cpdd.1506","DOIUrl":"10.1002/cpdd.1506","url":null,"abstract":"This Phase I, randomized, multicenter, open-label, parallel-group, single-dose study assessed the relative bioavailability of the anti–interleukin-5 antibody depemokimab (100 mg) when administered subcutaneously via either a safety syringe device (SSD) or an autoinjector (AI). Healthy adult participants were randomized I:I to SSD or AI treatment arms and I:I:I to the injection site (upper arm, abdomen, or thigh). Participants were followed up for 30 weeks; blood samples were collected for pharmacokinetic (PK) assessment before dosing on Day 1 and up to Week 26. Depemokimab concentration profile as measured by plasma maximum concentration (Cmax), the area under the concentration–time curve from time zero extrapolated to infinity (AUC0-inf), PK parameters, immunogenicity, and safety were assessed. Overall, 140 participants were enrolled (n = 70 per arm). Mean plasma concentration-time profiles of depemokimab were similar in both treatment arms, regardless of the injection site, adjusted geometric mean AI:SSD ratios for Cmax and AUC0-inf were 1.03 and 1.03, respectively, with all 90% confidence intervals within the bioequivalence bounds of 0.80-1.25. PK parameters were comparable across treatment arms. Treatment-related adverse events were reported in 19% of SSD and 20% of AI participants, with headache being the most common across both arms; no adverse events led to study withdrawal. These results support the use of either SSD or AI for subcutaneous administration of depemokimab.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"190-199"},"PeriodicalIF":1.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058206","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}

引用次数: 0

Effect of High-Fat Diets on the Pharmacokinetics of Bedaquiline Fumarate Tablet: A Trial in Healthy Chinese Participants

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-26 DOI: 10.1002/cpdd.1517

Xuanxuan Wang, Xiaoyu Zhao, Shaomei Yang, Kun He, Qing Wen, Wenyu Zhang

{"title":"Effect of High-Fat Diets on the Pharmacokinetics of Bedaquiline Fumarate Tablet: A Trial in Healthy Chinese Participants","authors":"Xuanxuan Wang, Xiaoyu Zhao, Shaomei Yang, Kun He, Qing Wen, Wenyu Zhang","doi":"10.1002/cpdd.1517","DOIUrl":"10.1002/cpdd.1517","url":null,"abstract":"Bedaquiline is employed to treat multidrug-resistant and extensive drug-resistant tuberculosis by inhibiting the proton pump of adenosine triphosphate synthase in Mycobacterium tuberculosis. This study aims to investigate the effect of high-fat diets on the pharmacokinetics of bedaquiline through a single-center, open-label, randomized trial in healthy Chinese participants. Bedaquiline fumarate tablets were administered at a dosage of 100 mg under both fasted conditions and high-fat diet conditions. The concentrations were determined using liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated using a noncompartmental model. The high-fat diet group showed a maximum plasma concentration that exceeded that of the fasted group by more than 4-fold and an area under the concentration-time curve from time 0 to the last measurable point that was more than twice as high. Moreover, compared to the fasted group, the high-fat diet group exhibits significantly lower levels of apparent clearance, indicating that the high-fat diet markedly enhances the rate and extent of gastrointestinal absorption of bedaquiline. To optimize drug bioavailability and absorption and ensure safety, the administration of bedaquiline with food is recommended in accordance with clinical usage guidelines and expert consensus.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 4","pages":"292-297"},"PeriodicalIF":1.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045761","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 Food Intake or Coadministration With an Acid-Reducing Agent on Lenacapavir Pharmacokinetics Following Oral Administration

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-23 DOI: 10.1002/cpdd.1513

Renu Singh, Mark Shelton, Isabel Olson, John Ling, Steve West, Jeffrey A. Levy, Martin S. Rhee, Sandhya Girish, Ramesh Palaparthy

{"title":"Effect of Food Intake or Coadministration With an Acid-Reducing Agent on Lenacapavir Pharmacokinetics Following Oral Administration","authors":"Renu Singh, Mark Shelton, Isabel Olson, John Ling, Steve West, Jeffrey A. Levy, Martin S. Rhee, Sandhya Girish, Ramesh Palaparthy","doi":"10.1002/cpdd.1513","DOIUrl":"10.1002/cpdd.1513","url":null,"abstract":"Lenacapavir is a potent, long-acting HIV-1 capsid inhibitor used in combination with other antiretrovirals to treat HIV-1 infection. The pharmacokinetics of orally administered drugs may be affected by food intake or coadministration of acid-reducing agents (ARA). Two Phase 1 studies were conducted on healthy participants to evaluate the effect of food and the impact of the histamine H2-receptor antagonist famotidine in parallel cohorts. In Study 1, oral lenacapavir (300 mg) was administered under fasting conditions, after a standardized high-fat meal, and after a low-fat meal (n = 8/cohort). In Study 2, lenacapavir 300 mg was administered alone (n = 27) and 2 hours after famotidine (40 mg; n = 25), each under fasting conditions. For the high-fat meal versus fasted comparison, the percentage geometric least-squares mean (%GLSM) ratios for the lenacapavir area under the curve to infinity (AUCinf) and maximum concentration (Cmax) were 115.2 and 145.2, respectively. For the low-fat meal, the %GLSM ratios for lenacapavir AUCinf and Cmax were 98.6 and 115.8, respectively, versus the fasted state. In the famotidine study, the %GLSM ratio for lenacapavir AUC from time zero to the last quantifiable concentration was 137.4, and for Cmax was 100.6. Based on available clinical safety data, the exposure increases observed in these studies were not expected to be clinically relevant. Overall, these data support the dosing of oral lenacapavir without regard to food intake or coadministration with ARAs.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 4","pages":"324-332"},"PeriodicalIF":1.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022480","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