PF-06282999 / Pfizer - LARVOL DELTA

An Integrated Approach Combining Experimental, Informatics and Energetic Methods for Solid Form Derisking of PF-06282999. (PubMed, J Pharm Sci) - "Herein, we describe the use of a combined approach consisting of experiments, informatics together with energetic calculations in analysis of four competing polymorphs of PF-06282999, a myeloperoxidase (MPO) inhibitor with conformational flexibility and multiple plausible hydrogen bond networks. This combined approach offered a comprehensive understanding of the solid form structure, properties, and performance, ensuring robust solid form derisking and selection."

Journal • MPO

Myeloperoxidase inhibition in mice alters atherosclerotic lesion composition. (PubMed, PLoS One) - "To assess non-invasive monitoring of plaque inflammation, [18F]-Fluoro-deoxy-glucose (FDG) was administered to Ldlr-/- mice with established atherosclerosis that had been treated with clinically relevant doses of PF-06282999, and reduced FDG signal was observed in animals treated with a dose of PF-06282999 that corresponded with reduced necrotic core area. These data suggest that MPO inhibition does not alter atherosclerotic plaque area or leukocyte homing, but rather alters the inflammatory tone of atherosclerotic lesions; thus, MPO inhibition could have utility to promote atherosclerotic lesion stabilization and prevent atherosclerotic plaque rupture."

Journal • Preclinical

A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model (clinicaltrials.gov) - P1; N=23; Terminated; Sponsor: Pfizer; N=36 ➔ 23; Suspended ➔ Terminated

Clinical • Enrollment change • Trial termination

A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model (clinicaltrials.gov) - P1; N=36; Active, not recruiting; Sponsor: Pfizer; Trial primary completion date: Jun 2014 ➔ Sep 2015

Clinical • Trial primary completion date

A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model (clinicaltrials.gov) - P1; N=36; Active, not recruiting; Sponsor: Pfizer; Trial primary completion date: Apr 2014 ➔ Jun 2014

Clinical • Trial primary completion date

A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model (clinicaltrials.gov) - P1; N=36; Active, not recruiting; Sponsor: Pfizer; Trial completion date: Apr 2014 ➔ Jun 2014

Clinical • Trial completion date

A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model (clinicaltrials.gov) - P1; N=36; Active, not recruiting; Sponsor: Pfizer; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Pfizer; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Pfizer

Clinical • New P1 trial

Establishing Transcriptional Signatures to Differentiate PXR-, CAR- and AhR-Mediated Regulation of Drug Metabolism and Transport Genes in Cryopreserved Human Hepatocytes. (PubMed, J Pharmacol Exp Ther) - "...The goal of this research was to establish PXR-/CAR-/AhR-specific drug-metabolizing enzyme (DME) and transporter gene expression signatures in sandwich-cultured cryopreserved human hepatocytes using selective activators of PXR (rifampin), CAR (CITCO), and AhR (omeprazole)...Subsequently, DME gene expression signatures were generated for known CYP3A4 inducers PF-06282999 and pazopanib...These results demonstrate that involvement of PXR vs. CAR vs. AhR can be identified via expression changes of signature DME and transporter genes. Inclusion of such key signature genes in could serve to simultaneously identify potential inducers and inhibitors, and the NRs involved in the transcriptional regulation, thus providing a more holistic and mechanism-based assessment of DDI risk."

Journal