PMID- 29688615
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20211204
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 8
IP  - 1
DP  - 2019 Jan
TI  - Comparative Pharmacokinetics and Pharmacodynamics of Bococizumab Following a 
      Single Subcutaneous Injection Using Drug Substance Manufactured at Two Sites or 
      Administration via Two Different Devices.
PG  - 40-48
LID - 10.1002/cpdd.454 [doi]
AB  - The pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a proprotein 
      convertase subtilisin/kexin type 9 (PCSK9) inhibitor, were compared following a 
      single 150-mg subcutaneous dose administered to healthy subjects 
      (n = 156-158/arm) via: (1) a prefilled syringe (PFS) using drug substance (DS) 
      manufactured by Pfizer, (2) a PFS using DS manufactured by Boehringer Ingelheim 
      Pharma, (3) a prefilled pen using DS manufactured by Pfizer (NCT02458209). Blood 
      samples were collected for 12 weeks postdose. Safety was monitored throughout. 
      Mean maximum plasma concentration (C(max) ) ranged between 11.0 and 11.3 mug/mL, 
      and area under the plasma concentration-time curve (AUC(inf) ) ranged between 
      177.6 and 185.0 mug.day/mL across treatments. The 90% confidence intervals for the 
      ratios of adjusted geometric means for C(max) and AUC(inf) fell within the 
      80%-125% range for both DS and delivery device comparisons. Comparable 
      low-density lipoprotein cholesterol profiles were observed, with nadir values of 
      54.3-56.1 mg/dL across treatments. Similar PCSK9 responses were also observed. 
      Safety profiles were similar across treatments, and the majority of adverse 
      events (AEs) were mild. Three subjects reported serious AEs. The most frequently 
      reported AEs were headache, injection-site reaction, and upper respiratory tract 
      infection, with no clear differences across treatments. Comparable PK, PD, and 
      safety were observed following a single bococizumab 150-mg subcutaneous injection 
      regardless of site of DS manufacture or delivery device used.
CI  - (c) 2018, The American College of Clinical Pharmacology.
FAU - Wang, Ellen Q
AU  - Wang EQ
AD  - Clinical Pharmacology, Global Product Development, Pfizer Inc., New York, NY, 
      USA.
FAU - Plotka, Anna
AU  - Plotka A
AD  - Global Biometrics and Data Management, Global Product Development, Pfizer Inc., 
      Collegeville, PA, USA.
FAU - Salageanu, Joanne
AU  - Salageanu J
AD  - Clinical Pharmacology, Global Product Development, Pfizer Inc., Groton, CT, USA.
FAU - Baltrukonis, Daniel
AU  - Baltrukonis D
AD  - Clinical Pharmacology, Global Product Development, Pfizer Inc., Groton, CT, USA.
FAU - Mridha, Khurshid
AU  - Mridha K
AD  - Science Recruitment Group Ltd., Furness Quay, Salford, Manchester, UK.
FAU - Frederich, Robert
AU  - Frederich R
AD  - Clinical Development and Operations, Global Product Development, Pfizer Inc., 
      Collegeville, PA, USA.
FAU - Sullivan, Beth E
AU  - Sullivan BE
AD  - Clinical Development and Operations, Global Product Development, Pfizer Inc., 
      Groton, CT, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02458209
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180424
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (PCSK9 Inhibitors)
RN  - 45M75JVK38 (bococizumab)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*administration & 
      dosage/blood/pharmacokinetics/pharmacology
MH  - Anticholesteremic Agents/*administration & 
      dosage/blood/pharmacokinetics/pharmacology
MH  - Cholesterol, LDL/blood
MH  - Female
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - PCSK9 Inhibitors
MH  - Proprotein Convertase 9/blood
MH  - Syringes
OTO - NOTNLM
OT  - LDL-C
OT  - PCSK9
OT  - bococizumab
OT  - monoclonal antibody
OT  - pharmacodynamics
OT  - pharmacokinetics
EDAT- 2018/04/25 06:00
MHDA- 2020/03/24 06:00
CRDT- 2018/04/25 06:00
PHST- 2017/09/22 00:00 [received]
PHST- 2018/02/06 00:00 [accepted]
PHST- 2018/04/25 06:00 [pubmed]
PHST- 2020/03/24 06:00 [medline]
PHST- 2018/04/25 06:00 [entrez]
AID - 10.1002/cpdd.454 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2019 Jan;8(1):40-48. doi: 10.1002/cpdd.454. Epub 2018 
      Apr 24.