Clinical Pharmacology in Drug Development最新文献_第7页

Food Effect and Pharmacokinetic Bridging of Avacopan in Caucasian and Japanese Healthy Participants 高加索人和日本人健康参与者的食物效应和药代动力学桥接作用

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-11 DOI: 10.1002/cpdd.1436

Shichang Miao, Pirow Bekker, Danielle Armas, Mary Lor, Ryuzo Hanada, Shota Okamura, Yuko Umezawa, Ashit Trivedi

{"title":"Food Effect and Pharmacokinetic Bridging of Avacopan in Caucasian and Japanese Healthy Participants","authors":"Shichang Miao, Pirow Bekker, Danielle Armas, Mary Lor, Ryuzo Hanada, Shota Okamura, Yuko Umezawa, Ashit Trivedi","doi":"10.1002/cpdd.1436","DOIUrl":"10.1002/cpdd.1436","url":null,"abstract":"Avacopan 30 mg twice daily (BID) is approved for the treatment of severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis). Food effect on avacopan pharmacokinetics (PKs) and PK bridging in Japanese participants were examined through 2 phase 1 studies involving healthy adult participants. In Study 1, an open-label, crossover trial, participants received oral administration of a single 30-mg dose of avacopan under fasted and fed conditions. Study 2 was a randomized, single-blind, placebo-controlled trial in Caucasian and Japanese participants: Part A investigated single doses of 10 and 30 mg of avacopan under fasted and fed conditions and Part B investigated 30 and 50 mg BID avacopan. The PKs of single-dose administrations of 10 and 30 mg in Japanese participants was compared with that in Caucasian participants under fasted conditions. Food substantially increased plasma avacopan area under the plasma concentration-time curve from time 0 to time infinity (AUC0-inf) by 1.72-fold, supporting the recommendation of taking avacopan with food. Maximum plasma concentration (Cmax) remained relatively unchanged. The median time to reach Cmax (tmax) was delayed by 3 hours. No significant food effect was observed on the active metabolite CCX168-M1 (M1) AUC. Avacopan and M1 exposures were <1.5-fold higher in Japanese participants than in Caucasian participants following multiple-dose administration of avacopan.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"1011-1023"},"PeriodicalIF":1.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589829","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 and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase 1 Randomized Clinical Trial in Healthy Humans 心肌再灌注损伤联合抗氧化疗法的安全性和药代动力学：健康人的 I 期随机临床试验》。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-08 DOI: 10.1002/cpdd.1443

Abraham I.J. Gajardo Cortez, José Lillo-Moya, Daniel San-Martín-Martinez, Josue Pozo-Martinez, Pablo Morales, Juan C. Prieto, Rubén Aguayo, Ángel Puentes, Cristobal Ramos, Solange Silva, Mabel Catalán, Karla Ramos, Claudio Olea-Azar, Ramón Rodrigo

{"title":"Safety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase 1 Randomized Clinical Trial in Healthy Humans","authors":"Abraham I.J. Gajardo Cortez, José Lillo-Moya, Daniel San-Martín-Martinez, Josue Pozo-Martinez, Pablo Morales, Juan C. Prieto, Rubén Aguayo, Ángel Puentes, Cristobal Ramos, Solange Silva, Mabel Catalán, Karla Ramos, Claudio Olea-Azar, Ramón Rodrigo","doi":"10.1002/cpdd.1443","DOIUrl":"10.1002/cpdd.1443","url":null,"abstract":"Myocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia-reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N-acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90-minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N-acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P < .05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric-reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P < .001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"1051-1060"},"PeriodicalIF":1.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554337","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

SERENE ER Analysis Part 2 SERENE-UC: Exposure-response Analysis of Higher Versus Standard Adalimumab Dosing Regimens for Patients with Moderately to Severely Active Ulcerative Colitis SERENE ER 分析第 2 部分 SERENE-UC：针对中度至重度活动性溃疡性结肠炎患者的阿达木单抗高剂量与标准剂量方案的暴露-反应分析。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-02 DOI: 10.1002/cpdd.1437

Sven Stodtmann, Mong-Jen Chen, Ana Victoria Ponce-Bobadilla, Tricia K. Finney-Hayward, Jasmina Kalabic, Nael M. Mostafa

{"title":"SERENE ER Analysis Part 2 SERENE-UC: Exposure-response Analysis of Higher Versus Standard Adalimumab Dosing Regimens for Patients with Moderately to Severely Active Ulcerative Colitis","authors":"Sven Stodtmann, Mong-Jen Chen, Ana Victoria Ponce-Bobadilla, Tricia K. Finney-Hayward, Jasmina Kalabic, Nael M. Mostafa","doi":"10.1002/cpdd.1437","DOIUrl":"10.1002/cpdd.1437","url":null,"abstract":"SERENE UC (NCT02065622) evaluated whether a higher adalimumab induction regimen improved patients with ulcerative colitis (UC) response, but a flat dose-response relationship was found in the induction study. We investigated exposure-response (ER) relationships in induction and maintenance studies considering patients’ baseline characteristics. Adalimumab exposures were simulated using the established population pharmacokinetic model. Multivariable logistic regressions were used to assess the efficacy endpoints (clinical remission, endoscopic remission, endoscopic improvement) at weeks 8 and 52. In the induction study, an increasing ER trend with heterogeneity between induction regimens was shown, suggesting average concentration (Cavg) had a significant impact on primary efficacy endpoints within each group. However, data were not described by a single ER curve. Using inverse effective clearance as the exposure metric described trends across induction regimens with a single curve. Patients with inherently lower effective adalimumab clearance responded better. The patient response rates at week 52 showed no heterogeneity. A short-term increase in adalimumab dose did not drive better responses for induction, and apparent ER relationships were better explained by patient-inherent lower clearance. Conversely, during maintenance up to week 52, increasing the concentration via dose translated to better responses more robustly. The ER findings for SERENE UC were consistent with SERENE CD.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"1033-1043"},"PeriodicalIF":1.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491170","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

SERENE ER Analysis Part 1-SERENE CD: Exposure-Response Analysis of Higher Versus Standard Adalimumab Dosing Regimens for Patients With Moderately to Severely Active Crohn Disease SERENE ER 分析第 1 部分--SERENE CD：中度至重度活动性克罗恩病患者阿达木单抗高剂量与标准剂量方案的暴露-反应分析。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-02 DOI: 10.1002/cpdd.1438

Mong-Jen Chen, Ana Victoria Ponce-Bobadilla, Sven Stodtmann, Alexandra P. Song, Tricia K. Finney-Hayward, Nael M. Mostafa

{"title":"SERENE ER Analysis Part 1-SERENE CD: Exposure-Response Analysis of Higher Versus Standard Adalimumab Dosing Regimens for Patients With Moderately to Severely Active Crohn Disease","authors":"Mong-Jen Chen, Ana Victoria Ponce-Bobadilla, Sven Stodtmann, Alexandra P. Song, Tricia K. Finney-Hayward, Nael M. Mostafa","doi":"10.1002/cpdd.1438","DOIUrl":"10.1002/cpdd.1438","url":null,"abstract":"SERENE CD (NCT02065570) evaluated whether a higher adalimumab induction dose would improve patients with Crohn disease response and suggested a flat dose-response relationship for efficacy in the induction study. We investigated exposure-response relationships in induction and maintenance studies considering patients’ baseline characteristics. Adalimumab exposures were simulated using the established population pharmacokinetic model. Efficacy end points (clinical remission/endoscopic response) at Weeks 4, 12, and 56 were evaluated in exposure-response analyses using multivariable logistic regression. Analyses showed an increasing trend with heterogeneity between induction regimens, which suggested that average concentration has an impact on coprimary efficacy end points within each group, but data did not fit a single-response curve. Although higher concentrations within arms were associated with improved outcomes, increasing the concentration through a higher induction dose was not associated with increasing clinical remission/endoscopic response at Week 4/12. A model including inverse effective clearance eliminated heterogeneity and described trends across induction regimens with a single curve. In the maintenance study, the response rates at Week 56 showed no heterogeneity. In the induction study, patients with lower effective adalimumab clearance responded better, whereas in the maintenance study average concentration drove primary efficacy end points at Week 56. Research extending these findings to other indications is needed.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"1024-1032"},"PeriodicalIF":1.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491169","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

Comparative Bioequivalence Study of 2 Clopidogrel 75-mg Tablet Formulations in Moroccan Volunteers 摩洛哥志愿者服用两种氯吡格雷 75 毫克片剂的生物等效性比较研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-06-26 DOI: 10.1002/cpdd.1442

Aimen El Orche, Choukri El Khabbaz, Amine Cheikh, Houda Bouchafra, Samira Jawhari, Faouzi My El Abbes, Yahya Cherrah

{"title":"Comparative Bioequivalence Study of 2 Clopidogrel 75-mg Tablet Formulations in Moroccan Volunteers","authors":"Aimen El Orche, Choukri El Khabbaz, Amine Cheikh, Houda Bouchafra, Samira Jawhari, Faouzi My El Abbes, Yahya Cherrah","doi":"10.1002/cpdd.1442","DOIUrl":"10.1002/cpdd.1442","url":null,"abstract":"This study investigates the pharmacokinetic properties and bioequivalence of 2 formulations of clopidogrel tablets administered to a cohort of healthy Moroccan male volunteers. The primary objective was to assess the rate and extent of drug absorption from the test formulation in comparison to a reference formulation, focusing on critical parameters including maximum plasma concentration (Cmax), area under the concentration-time curve from 0 to the last measurable time (AUC0-t), and area under the concentration-time curve extrapolated to infinity (AUC0-∞). The results revealed that the geometric mean ratios of Cmax, AUC0-t, and AUC0–∞ for the test formulation relative to the reference formulation were 105.7%, 105.6%, and 105.6%, respectively. The 90% confidence intervals for these parameters fell within the predefined bioequivalence range of 80%-125%, indicating a statistically and clinically equivalent performance between the 2 formulations. This investigation sheds light on the pharmacokinetic behavior of clopidogrel in the context of the Moroccan male population, offering valuable insights into the comparability of formulations.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"1044-1050"},"PeriodicalIF":1.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455762","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 Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti-Wolbachia Candidate Macrofilaricide AWZ1066S--一种抗狼鞭毛虫候选大丝虫杀虫剂的 1 期随机、双盲、安慰剂对照、单剂量递增试验。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-06-24 DOI: 10.1002/cpdd.1441

Graham Devereux, Marcin Bula, Karen Tripp, Richard Fitzgerald, Nicola Eraut, Muhammad Salman Alam, Tomoyuki Moriyama, Raku Shinkyo, Lauren Walker, Duolao Wang, Fabian Gusovsky, Jeannette van der Velde, Joseph D. Turner, Weiqian David Hong, Paul M. O'Neill, Mark J. Taylor, Stephen A. Ward

{"title":"A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti-Wolbachia Candidate Macrofilaricide","authors":"Graham Devereux, Marcin Bula, Karen Tripp, Richard Fitzgerald, Nicola Eraut, Muhammad Salman Alam, Tomoyuki Moriyama, Raku Shinkyo, Lauren Walker, Duolao Wang, Fabian Gusovsky, Jeannette van der Velde, Joseph D. Turner, Weiqian David Hong, Paul M. O'Neill, Mark J. Taylor, Stephen A. Ward","doi":"10.1002/cpdd.1441","DOIUrl":"10.1002/cpdd.1441","url":null,"abstract":"AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase 1, first-in-human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double-blind, placebo-controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700-mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"1071-1081"},"PeriodicalIF":1.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455759","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

A Randomized, Cross-Over Study Investigating the Comparability of Somatrogon-ghla in 2 Different Drug Product Presentations 一项随机交叉研究调查了两种不同药物产品中 Somatrogon-ghla 的可比性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-06-24 DOI: 10.1002/cpdd.1434

Allison Manners, Joan Korth-Bradley, Michael P. Wajnrajch

{"title":"A Randomized, Cross-Over Study Investigating the Comparability of Somatrogon-ghla in 2 Different Drug Product Presentations","authors":"Allison Manners, Joan Korth-Bradley, Michael P. Wajnrajch","doi":"10.1002/cpdd.1434","DOIUrl":"10.1002/cpdd.1434","url":null,"abstract":"Somatrogon-ghla is a long-acting, recombinant human growth hormone approved for the treatment of pediatric patients with growth hormone deficiency. Forty-nine healthy, adult males were enrolled in a randomized, crossover study to compare somatrogon exposure after subcutaneous doses administered using a frozen vial presentation or a prefilled, multiple dose pen. Somatrogon, insulin-like growth factor-I, and IGF-1 binding protein-3 concentrations were collected for up to 240 hours post dose to assess pharmacokinetic and pharmacodynamic responses. There was a 2-week washout between administration of the doses. Seven participants did not complete the study due to withdrawal of consent (n = 2) or loss to follow-up. Two treatment-emergent adverse events, headaches, were judged by the investigator as possibly related to study drug administration. Both were mild. Injection site reactions were observed in 6/48 participants after administration with the pen and 12/46 after administration using the vial. Drug and biomarker concentrations were assessed using validated assays and noncompartmental methods were used to determine pharmacokinetic and pharmacodynamic parameters. Bioequivalence was demonstrated for somatrogon area under the concentration-time curve, but not for the peak somatrogon concentration, where the lower limit of the 90% confidence interval for the ratio of pen/vial was 74.2%, which is less than the lower limit, 80.0%, dictated by bioequivalence criteria. The IGF-1 responses were largely within bioequivalence limits. It was concluded that the 2 formulations are comparable.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1108-1114"},"PeriodicalIF":1.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455760","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

Bioequivalence of Recombinant Human Teriparatide Injection in Healthy Adult Female Subjects in the Fasting State 空腹状态下重组人特立帕肽注射液在健康成年女性受试者中的生物等效性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-06-24 DOI: 10.1002/cpdd.1440

Shengling Hu, Yalei Wen, Jing Li, Wenming Chen, Yichuan Bai, Fengyun Gong

{"title":"Bioequivalence of Recombinant Human Teriparatide Injection in Healthy Adult Female Subjects in the Fasting State","authors":"Shengling Hu, Yalei Wen, Jing Li, Wenming Chen, Yichuan Bai, Fengyun Gong","doi":"10.1002/cpdd.1440","DOIUrl":"10.1002/cpdd.1440","url":null,"abstract":"A single-center, randomized, open, 2-period, self-crossover, single-dose trial was conducted to evaluate the bioequivalence of the test (T) and reference (R) preparations in healthy adult female subjects under fasting conditions. Seventy-six subjects were enrolled in the study, and subjects were randomly divided into 2 groups at a 1:1 ratio and were administered once per period, with a 4-day washout period. In each period, plasma drug concentrations, blood calcium changes, and antibodies were determined for pharmacokinetics, pharmacodynamics, and immunogenicity analysis, respectively, and adverse events were recorded for safety analysis. The 90% confidence intervals for the geometric mean ratios (T:R) of maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the last measurable concentration, and area under the plasma concentration-time curve from time 0 to infinity were within the predefined bioequivalence criterion of 80%-125%, indicating bioequivalence between the T and R preparations under fasting conditions. Comparable serum calcium levels demonstrated pharmacodynamics similarity, and no differences were found in immunogenicity profiles. Additionally, the incidence of adverse reactions to the T preparation was 18.4% lower than that of the R preparation (31.6%). This study confirmed the bioequivalence of the T and R preparations under fasting conditions, along with comparable immunogenicity profiles and good safety.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1151-1156"},"PeriodicalIF":1.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455761","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

Impact of Food on the Oral Absorption of N-Acetyl-D-Mannosamine in Healthy Men and Women 食物对健康男性和女性口服 N-乙酰基-D-甘露糖胺吸收的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-06-20 DOI: 10.1002/cpdd.1433

Allan M. Evans, Gianfranco Fornasini, Tahlia R. Meola, William A. Gahl, Marjan Huizing, Thomas M. Polasek, Stephanie E. Reuter

{"title":"Impact of Food on the Oral Absorption of N-Acetyl-D-Mannosamine in Healthy Men and Women","authors":"Allan M. Evans, Gianfranco Fornasini, Tahlia R. Meola, William A. Gahl, Marjan Huizing, Thomas M. Polasek, Stephanie E. Reuter","doi":"10.1002/cpdd.1433","DOIUrl":"10.1002/cpdd.1433","url":null,"abstract":"N-Acetyl-D-mannosamine (ManNAc) is an endogenous monosaccharide and precursor of N-acetylneuraminic acid (Neu5Ac), a critical sialic acid. ManNAc is currently under clinical development to treat GNE myopathy, a rare muscle-wasting disease. In this randomized, open-label, 2-sequence, crossover study, 16 healthy women and men were administered a single oral dose of ManNAc under fasting and fed conditions. Blood samples were collected for 48 hours after dosing for quantification of plasma ManNAc and Neu5Ac concentrations. Noncompartmental pharmacokinetic and deconvolution analyses were performed using baseline-corrected plasma concentration data. Administration of ManNAc in the fed state resulted in a 1.6-fold increase in ManNAc exposure, compared to fasting conditions. A concurrent increase in Neu5Ac exposure was observed in the presence of food. Deconvolution analysis indicated that the findings were attributed to prolonged absorption rather than an enhanced rate of absorption. The impact of food on ManNAc pharmacokinetics was greater in women than men (fed/fasted area under the concentration-time curve from time 0 to infinity mean ratio: 198% compared to 121%). It is hypothesized that the presence of food slows gastric emptying, allowing a gradual release of ManNAc into the small intestine, translating into improved ManNAc absorption. The results suggest that taking ManNAc with food may enhance its therapeutic activity and/or reduce the daily dosage requirement.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 8","pages":"876-883"},"PeriodicalIF":1.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426507","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

Bioequivalence Study of Velpatasvir/Sofosbuvir Oral Coated Tablets in Healthy Volunteers Under Fasting Conditions 健康志愿者在空腹条件下服用韦帕他韦/索非布韦口服包衣片的生物等效性研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-06-16 DOI: 10.1002/cpdd.1435

Sergei Noskov, Anna Arefeva, Kseniia Radaeva, Igor Makarenko, Maria Gefen, Roman Drai

{"title":"Bioequivalence Study of Velpatasvir/Sofosbuvir Oral Coated Tablets in Healthy Volunteers Under Fasting Conditions","authors":"Sergei Noskov, Anna Arefeva, Kseniia Radaeva, Igor Makarenko, Maria Gefen, Roman Drai","doi":"10.1002/cpdd.1435","DOIUrl":"10.1002/cpdd.1435","url":null,"abstract":"This study was conducted as a single-site, open-label, randomized, replicated crossover trial with 4 treatment periods. The aim was to evaluate the bioequivalence of a generic test drug containing velpatasvir and sofosbuvir compared to an established brand-name medication in healthy White subjects under fasting conditions. Blood samples were collected at specified intervals up to 72 hours after dosing to measure the concentrations of velpatasvir and sofosbuvir using a certified high-performance liquid chromatography with tandem mass spectrometry method. The bioequivalence of the 2 formulations was confirmed when statistical analysis showed that confidence intervals for the log-transformed peak concentration and area under the concentration-time curve from time 0 to the last quantifiable sample were within an acceptable range from 80% to 125%. Criteria for bioequivalence were met for both area under the concentration-time curve from time 0 until the last quantifiable sample and peak concentration parameters. No adverse effects were reported during this trial in both groups.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1123-1129"},"PeriodicalIF":1.5,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330465","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