PMID- 28539539
OWN - NLM
STAT- MEDLINE
DCOM- 20180613
LR  - 20221207
IS  - 1347-4820 (Electronic)
IS  - 1346-9843 (Linking)
VI  - 81
IP  - 10
DP  - 2017 Sep 25
TI  - Efficacy and Safety of Bococizumab (RN316/PF-04950615), a Monoclonal Antibody 
      Against Proprotein Convertase Subtilisin/Kexin Type 9, in Hypercholesterolemic 
      Japanese Subjects Receiving a Stable Dose of Atorvastatin or Treatment-Naive　- 
      Results From a Randomized, Placebo-Controlled, Dose-Ranging Study.
PG  - 1496-1505
LID - 10.1253/circj.CJ-16-1310 [doi]
AB  - BACKGROUND: A Phase 2, dose-ranging study of bococizumab, a monoclonal 
      anti-proprotein convertase subtilisin/kexin type 9 antibody, was conducted in 
      Japanese subjects to assess its efficacy, safety, and tolerability in this 
      population.Methods and Results:Two different hypercholesterolemic study 
      populations were enrolled concurrently: Japanese subjects with uncontrolled 
      low-density lipoprotein cholesterol (LDL-C) despite atorvastatin treatment (LDL-C 
      >/=100 mg/dL; n=121), and Japanese subjects naive to lipid-lowering agents and with 
      LDL-C >/=130 mg/dL (n=97). Subjects within each study population were randomized to 
      bococizumab 50, 100, or 150 mg, or placebo, q14D for 16 weeks; an open-label 
      ezetimibe 10 mg daily arm was also included for the atorvastatin-treated 
      population. Significant, dose-dependent reductions in fasting LDL-C levels were 
      observed in all bococizumab arms of both study populations at Weeks 12 and 16 
      (adjusted mean percent changes from baseline: 54.1-76.7% for atorvastatin-treated 
      subjects and 47.7-66.8% for treatment-naive subjects; P<0.001 vs. placebo for 
      all). Bococizumab also caused dose-dependent changes in other lipid parameters in 
      both study populations at Weeks 12 and 16. No serious adverse events (AEs) 
      related to bococizumab treatment occurred and all treatment-emergent AEs were 
      mild or moderate in severity. No dose-dependent relationship between bococizumab 
      treatment and development of anti-drug antibodies was observed. CONCLUSIONS: 
      Bococizumab was well tolerated and significantly reduced fasting LDL-C in 
      atorvastatin-treated and treatment-naive hypercholesterolemic Japanese subjects. 
      (Clinicaltrials.gov identifier: NCT02055976.).
FAU - Yokote, Koutaro
AU  - Yokote K
AD  - Department of Clinical Cell Biology and Medicine, Chiba University Graduate 
      School of Medicine.
FAU - Kanada, Shigeto
AU  - Kanada S
AD  - Heishinkai Medical Group Incorporated.
FAU - Matsuoka, Osamu
AU  - Matsuoka O
AD  - ToCROM Clinic, Heishinkai Medical Group Incorporated.
FAU - Sekino, Hisakuni
AU  - Sekino H
AD  - Sekino Hospital.
FAU - Imai, Keiji
AU  - Imai K
AD  - Development Japan, Pfizer Japan Inc.
FAU - Tabira, Junichi
AU  - Tabira J
AD  - Development Japan, Pfizer Japan Inc.
FAU - Matsuoka, Nobushige
AU  - Matsuoka N
AD  - Development Japan, Pfizer Japan Inc.
FAU - Chaudhuri, Sandip
AU  - Chaudhuri S
AD  - Worldwide Research and Development, Pfizer Ltd.
FAU - Teramoto, Tamio
AU  - Teramoto T
AD  - Teikyo Academic Research Center, Teikyo University.
LA  - eng
SI  - ClinicalTrials.gov/NCT02055976
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170523
PL  - Japan
TA  - Circ J
JT  - Circulation journal : official journal of the Japanese Circulation Society
JID - 101137683
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Cholesterol, LDL)
RN  - 45M75JVK38 (bococizumab)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
SB  - IM
CIN - Circ J. 2017 Sep 25;81(10 ):1386-1387. PMID: 28579602
MH  - Aged
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/pharmacology
MH  - Anticholesteremic Agents/therapeutic use
MH  - Asian People
MH  - Atorvastatin/therapeutic use
MH  - Cholesterol, LDL/blood/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Hypercholesterolemia/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Proprotein Convertase 9/immunology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Bococizumab
OT  - Hypercholesterolemia
OT  - Japan
OT  - PCSK9 inhibitor
OT  - Phase 2 study
EDAT- 2017/05/26 06:00
MHDA- 2018/06/14 06:00
CRDT- 2017/05/26 06:00
PHST- 2017/05/26 06:00 [pubmed]
PHST- 2018/06/14 06:00 [medline]
PHST- 2017/05/26 06:00 [entrez]
AID - 10.1253/circj.CJ-16-1310 [doi]
PST - ppublish
SO  - Circ J. 2017 Sep 25;81(10):1496-1505. doi: 10.1253/circj.CJ-16-1310. Epub 2017 
      May 23.