PMID- 32729822
OWN - NLM
STAT- MEDLINE
DCOM- 20200915
LR  - 20200915
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 58
IP  - 10
DP  - 2020 Oct
TI  - Pharmacokinetic/pharmacodynamic and safety study of a single dose of evolocumab 
      140 mg in healthy Chinese subjects.
PG  - 557-564
LID - 10.5414/CP203765 [doi]
AB  - OBJECTIVE: Evolocumab, a human monoclonal antibody that binds to proprotein 
      convertase subtilisin/kexin type 9 (PCSK9), markedly reduces low-density 
      lipoprotein cholesterol (LDL-C). Here we characterize the pharmacokinetics, 
      pharmacodynamics, safety, and tolerability of evolocumab manufactured at a new 
      site administered in healthy Chinese subjects. MATERIALS AND METHODS: This phase 
      1 study of a single subcutaneous 140-mg dose of evolocumab was conducted in 
      healthy subjects of Chinese descent residing in Hong Kong. Subjects were followed 
      through day 85. RESULTS: 20 subjects (all men) were enrolled. Mean (SD) age was 
      26.6 (8.5) years; baseline LDL-C was 2.4 (0.7) mmol/L. Mean (SD) evolocumab 
      maximum serum concentration (C(max)) was 14.1 (5.0) mug/mL; area under the serum 
      drug concentration-time curve from time 0 to time of last quantifiable 
      concentration (AUC(last)) was 178 (80) dayxmug/mL; AUC from time 0 to infinity 
      (AUC(inf)) was 187 (80) dayxmug/mL; terminal half-life was 5.95 (1.76) days; 
      median time to reach C(max) (t(max)) was 4.0 days. Maximum LDL-C decrease 
      (-57.5%) was observed on day 15 and recovered to baseline by day 57. The most 
      common adverse events (AEs) were nasal congestion (20%), oropharyngeal pain 
      (15%), sneezing (15%), cough (10%), upper respiratory tract infection (10%), and 
      diarrhea (10%). Most AEs were isolated incidences of mild severity, with no 
      serious or treatment-related events. No anti-evolocumab antibodies were detected. 
      CONCLUSION: A single 140-mg dose of evolocumab manufactured at the new site and 
      administered in healthy Chinese subjects was associated with typical antibody 
      pharmacokinetics, rapid and reversible decreases in LDL-C, and no new safety 
      events.
FAU - Lu, Hong
AU  - Lu H
FAU - Yu, Zhigang
AU  - Yu Z
FAU - Hsu, Cheng-Pang
AU  - Hsu CP
FAU - Tomlinson, Brian
AU  - Tomlinson B
FAU - Luk, Andrea On Yan
AU  - Luk AOY
FAU - Egbuna, Ogo
AU  - Egbuna O
FAU - Wu, Jihua
AU  - Wu J
FAU - Abosaleem, Bassam
AU  - Abosaleem B
FAU - Rana, Jitesh
AU  - Rana J
FAU - Monsalvo, Maria Laura
AU  - Monsalvo ML
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Anticholesteremic Agents)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
RN  - LKC0U3A8NJ (evolocumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*pharmacology
MH  - Anticholesteremic Agents
MH  - Healthy Volunteers
MH  - Hong Kong
MH  - Humans
MH  - Male
MH  - Proprotein Convertase 9
MH  - Treatment Outcome
EDAT- 2020/07/31 06:00
MHDA- 2020/09/17 06:00
CRDT- 2020/07/31 06:00
PHST- 2020/09/11 00:00 [accepted]
PHST- 2020/07/31 06:00 [pubmed]
PHST- 2020/09/17 06:00 [medline]
PHST- 2020/07/31 06:00 [entrez]
AID - 187010 [pii]
AID - 10.5414/CP203765 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2020 Oct;58(10):557-564. doi: 10.5414/CP203765.