A Phase 2, Randomized, Parallel, Open-Label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Various Dosing Regimens of Single-Agent Belantamab Mafodotin (GSK2857916) in Participants with Relapsed or Refractory Multiple Myeloma (DREAMM-14) - Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants with Relaps

开始日期2022-02-18

申办/合作机构

GlaxoSmithKline Research & Development

EUCTR2021-000007-21-IT / Unknown status临床3期

A two-part, randomized, placebo controlled, double blind, multicenter, Phase 3 study to evaluate the efficacy and safety of linerixibat for the treatment of cholestatic pruritus in participants with primary biliary cholangitis (PBC). - PH3a,linerixibat vsPBO,efficacy&safety,itch study for the treatment of cholestatic pruritus in PBC

开始日期2021-06-24

申办/合作机构

GlaxoSmithKline Research & Development

EUCTR2020-003612-28-IT / Unknown status临床3期

A 52-week, randomised, double-blind, double-dummy, parallel group,multicentre, non-inferiority study assessing exacerbation rate,additional measures of asthma control and safety in adult and adolescent severe asthmatic participants with an eosinophilic phenotype treated with GSK3511294 compared with mepolizumab or benralizumab - NA

开始日期2021-06-23

申办/合作机构

GlaxoSmithKline Research & Development

100 项与 GlaxoSmithKline Research & Development 相关的临床结果

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0 项与 GlaxoSmithKline Research & Development 相关的专利（医药）

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387

项与 GlaxoSmithKline Research & Development 相关的文献（医药）

2024-07-01·Drug Metabolism and Disposition

Survey of Pharmaceutical Industry’s Best Practices around In Vitro Transporter Assessment and Implications for Drug Development: Considerations from the International Consortium for Innovation and Quality for Pharmaceutical Development Transporter Working Group

Article

作者: Rollison, Helen E ; Chu, Xiaoyan ; Lai, Yurong ; Hanna, Imad ; Thakkar, Nilay ; Vergis, James M ; Liang, Xiaomin ; Park, Seong Hee ; Shen, Hong ; Chanteux, Hugues ; Fang, Zhizhou ; Xu, Christine ; Sane, Rucha ; Hillgren, Kathleen M ; Brumm, Jochen ; Costales, Chester ; Tohyama, Kimio ; Taskar, Kunal ; Li, Cindy Yanfei ; Bow, Daniel A J ; Hop, Cornelis E C A ; Taub, Mitchell ; Mitra, Pallabi ; Mahar, Kelly M ; Fenner, Katherine S ; Salphati, Laurent

The International Consortium for Innovation and Quality in Pharmaceutical Development Transporter Working Group had a rare opportunity to analyze a crosspharma collation of in vitro data and assay methods for the evaluation of drug transporter substrate and inhibitor potential. Experiments were generally performed in accordance with regulatory guidelines. Discrepancies, such as not considering the impact of preincubation for inhibition and free or measured in vitro drug concentrations, may be due to the retrospective nature of the dataset and analysis. Lipophilicity was a frequent indicator of crosstransport inhibition (P-gp, BCRP, OATP1B, and OCT1), with high molecular weight (MW ≥500 Da) also common for OATP1B and BCRP inhibitors. A high level of overlap in in vitro inhibition across transporters was identified for BCRP, OATP1B1, and MATE1, suggesting that prediction of DDIs for these transporters will be common. In contrast, inhibition of OAT1 did not coincide with inhibition of any other transporter. Neutrals, bases, and compounds with intermediate-high lipophilicity tended to be P-gp and/or BCRP substrates, whereas compounds with MW <500 Da tended to be OAT3 substrates. Interestingly, the majority of in vitro inhibitors were not reported to be followed up with a clinical study by the submitting company, whereas those compounds identified as substrates generally were. Approaches to metabolite testing were generally found to be similar to parent testing, with metabolites generally being equally or less potent than parent compounds. However, examples where metabolites inhibited transporters in vitro were identified, supporting the regulatory requirement for in vitro testing of metabolites to enable integrated clinical DDI risk assessment. SIGNIFICANCE STATEMENT: A diverse dataset showed that transporter inhibition often correlated with lipophilicity and molecular weight (>500 Da). Overlapping transporter inhibition was identified, particularly that inhibition of BCRP, OATP1B1, and MATE1 was frequent if the compound inhibited other transporters. In contrast, inhibition of OAT1 did not correlate with the other drug transporters tested.

2024-04-01·BioTechniques

An Industry Perspective Approach and Control Strategy for Implementation of Ready-to-Use Cells in Bioassays: Survey Outcome And Recommendations

Article

作者: Haenssen, Keneshia K ; White, John R ; Cheng, Zhijie Jey ; Wang, Jenny ; Kozminsky-Atias, Adi ; Ong, Esther HQ ; Martinez, Eva ; Qahwash, Isam ; Day, Peter ; Ahmed, Sammina ; Bennington, Petra ; Stokes, Elaine SE ; Amstrup, Jan

The BioPhorum Development Group is an industry collaboration enabling the sharing of common practices for the development of biopharmaceuticals. Bioassays are an important part of an analytical control system. Utilization of ready-to-use cells can increase operational flexibility and improve efficiency by providing frozen cell banks uniform stock while removing challenges associated with maintaining cultured cells. The BioPhorum Development Group-Bioassay workstream conducted an intercompany benchmarking survey and group discussions around the use of ready-to-use cells for bioassays. The results of the collaboration provide alignment on nomenclature, production, qualification and implementation of ready-to-use cells to support the assay life cycle.

2023-04-15·American Journal of Respiratory and Critical Care Medicine

NRF2 Activation Reprograms Defects in Oxidative Metabolism to Restore Macrophage Function in Chronic Obstructive Pulmonary Disease

Article

作者: Sadiku, Pranvera ; Dockrell, David H. ; Callahan, James F. ; Baillie, Kenneth ; Choudhury, Gourab ; Rodriguez Blanco, Giovanny ; McHugh, Brian J. ; Sanchez-Garcia, Manuel A. ; Howden, Andrew J. M. ; Rumsey, William ; Singh, Dave ; Coelho, Patricia ; Carmeliet, Peter ; Parkinson, Nicholas ; Ghesquiere, Bart ; Cooper, George ; McCafferty, John ; Vermaelen, Wesley ; Bewley, Martin ; Watts, Emily R. ; Whyte, Moira K. B. ; Von Kriegsheim, Alex ; Zhang, Ailiang ; Ryan, Eilise M. ; Walmsley, Sarah R. ; Cole, Joby ; Cantrell, Doreen A. ; Sanchez, Yolanda

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.

100 项与 GlaxoSmithKline Research & Development 相关的药物交易

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100 项与 GlaxoSmithKline Research & Development 相关的转化医学

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