Abstract
Three single-dose and one multiple-dose phase I studies were conducted in subjects with primary hypercholesterolemia to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of bococizumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. The dosing schedules for hypercholesterolemic subjects randomized in the four phase I studies were (1) ascending, single, intravenous (IV) bococizumab (0.3, 1, 3, 6, 12, or 18 mg/kg), or placebo (N = 48; baseline low-density lipoprotein cholesterol [LDL-C] ≥130 mg/dL); (2) single, IV bococizumab (0.5 or 4 mg/kg; no placebo) added to ongoing atorvastatin 40 mg/day (N = 24); (3) single, fixed, subcutaneous (SC) bococizumab (100 or 200 mg), or IV bococizumab (200 mg; no placebo; N = 49; baseline LDL-C ≥130 mg/dL); and (4) weekly IV bococizumab (0.25, 0.5, 1, or 1.5 mg/kg) or placebo for 4 weeks (N = 67; baseline LDL-C ≥130 mg/dL). Bococizumab pharmacokinetics were well characterized following single IV or SC doses and following multiple IV doses. Exposure to single-dose bococizumab increased slightly greater than dose-proportionally and clearance decreased with increasing dose. In the single-dose studies, maximal mean percent reductions from baseline in LDL-C...Continue Reading
References
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nabil G SeidahMichel Chretien
Apr 22, 2004·Clinical Genetics·T P Leren
Mar 24, 2006·The New England Journal of Medicine·Jonathan C CohenHelen H Hobbs
Nov 24, 2007·Journal of Lipid Research·Holly E CareskeyRobert J Konrad
Apr 9, 2009·The Journal of Clinical Endocrinology and Metabolism·Susan G LakoskiHelen H Hobbs
Oct 25, 2011·The Journal of Pharmacology and Experimental Therapeutics·Hong LiangDavid L Shelton
Feb 2, 2012·The Journal of Biological Chemistry·Javier Chaparro-RiggersArvind Rajpal
Mar 23, 2012·The New England Journal of Medicine·Evan A SteinGary D Swergold
Apr 3, 2012·Journal of the American College of Cardiology·James M McKenneyEvan A Stein
May 29, 2012·Lancet·Evan A SteinRobert Pordy
Oct 23, 2012·Journal of the American College of Cardiology·Clapton S DiasEvan A Stein
Nov 2, 2012·The New England Journal of Medicine·Eli M RothEvan A Stein
Apr 4, 2014·Journal of the American College of Cardiology·Erik StroesUNKNOWN GAUSS-2 Investigators
Apr 26, 2014·Future Cardiology·Eli M Roth, Philip Diller
Oct 6, 2014·Lancet·Frederick J RaalUNKNOWN TESLA Investigators
Mar 19, 2015·The American Journal of Cardiology·Christie M BallantyneHarold Bays
Jun 2, 2015·American Heart Journal·Dean J KereiakesHelen M Colhoun
Jan 21, 2016·Future Cardiology·Eli M Roth
May 22, 2016·Journal of Clinical Lipidology·Rishi K WadheraJoAnne M Foody
Jun 9, 2016·Vascular Health and Risk Management·Dirk J BlomPeter P Toth
Jul 21, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nicola FerriAlberto Corsini
Aug 9, 2016·Cardiovascular Research·Giuseppe Danilo NorataAlberico L Catapano
Aug 10, 2016·American Heart Journal·Paul M RidkerUNKNOWN Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Investigators
Jan 7, 2017·Expert Opinion on Biological Therapy·Nicola FerriMassimiliano Ruscica
Feb 10, 2017·Journal of Clinical Pharmacology·Chandrasekhar UdataXu Meng
Mar 18, 2017·The New England Journal of Medicine·Marc S SabatineUNKNOWN FOURIER Steering Committee and Investigators
Mar 18, 2017·The New England Journal of Medicine·Paul M RidkerUNKNOWN SPIRE Investigators
Mar 18, 2017·The New England Journal of Medicine·Paul M RidkerUNKNOWN SPIRE Cardiovascular Outcome Investigators
Mar 23, 2017·Clinical Cardiology·Seth J BaumKatherine Wilemon
Apr 13, 2017·Internal Medicine Journal·Daniel J SchererStephen J Nicholls
May 30, 2017·Expert Opinion on Biological Therapy·Nicola FerriMassimiliano Ruscica
Jun 6, 2017·The New England Journal of Medicine·Darren B TaichmanJoyce Backus
Citations
May 9, 2018·Drugs·Stefan Weisshaar, Markus Zeitlinger
Apr 25, 2018·Clinical Pharmacology in Drug Development·Ellen Q WangBeth E Sullivan
Sep 19, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ellen Q WangDaniel Baltrukonis
Oct 24, 2017·Cardiovascular Therapeutics·Sergio FazioBarry Gumbiner
Sep 18, 2020·Journal of Drug Assessment·Rasha KaddouraAmar M Salam
Oct 6, 2020·Heart Views : the Official Journal of the Gulf Heart Association·Rasha KaddouraAmar M Salam