Efficacy and safety of olezarsen in lowering apolipoprotein C-III and triglycerides in healthy Japanese Americans.
Antisense oligonucleotide
ApoC-III
Cardiovascular disease
Ethnicity
Pancreatitis
Triglycerides
Journal
Lipids in health and disease
ISSN: 1476-511X
Titre abrégé: Lipids Health Dis
Pays: England
ID NLM: 101147696
Informations de publication
Date de publication:
03 Oct 2024
03 Oct 2024
Historique:
received:
16
07
2024
accepted:
13
09
2024
medline:
4
10
2024
pubmed:
4
10
2024
entrez:
4
10
2024
Statut:
epublish
Résumé
Olezarsen is a GalNAc A randomized, placebo-controlled, double-blind phase 1 study was performed in 28 healthy Japanese American participants treated with olezarsen in single-ascending doses (SAD; 30, 60, 90 mg) or multiple doses (MD; 60 mg every 4 weeks for 4 doses). The primary, secondary, and exploratory objectives were safety and tolerability, pharmacokinetics, and effects of olezarsen on fasting serum triglycerides and apoC-III, respectively. There were 20 participants (16 active:4 placebo) in the SAD part of the study, and 8 participants (6 active:2 placebo) in the MD part of the study. For the primary endpoint, no serious adverse events or clinically relevant laboratory abnormalities were reported. The majority of olezarsen plasma exposure occurred within 24 h post-dose. In the SAD cohorts at Day 15 the percentage reduction in apoC-III/TG was - 39.4%/ - 17.8%, - 60.8%/ - 52.7%, and - 68.1%/ - 39.2% in the 30, 60 and 90 mg doses, respectively, vs 2.3%/44.5% increases in placebo. In the MD cohort, at Day 92 the percentage reduction in apoC-III/TG was - 81.6/ - 73.8% vs - 17.2/ - 40.8% reduction in placebo. Favorable changes were also present in VLDL-C, apoB and HDL-C. Single- and multiple-dose administration of olezarsen was safe, was well tolerated, and significantly reduced apoC-III and triglyceride levels in healthy Japanese Americans.
Sections du résumé
BACKGROUND
BACKGROUND
Olezarsen is a GalNAc
METHODS
METHODS
A randomized, placebo-controlled, double-blind phase 1 study was performed in 28 healthy Japanese American participants treated with olezarsen in single-ascending doses (SAD; 30, 60, 90 mg) or multiple doses (MD; 60 mg every 4 weeks for 4 doses). The primary, secondary, and exploratory objectives were safety and tolerability, pharmacokinetics, and effects of olezarsen on fasting serum triglycerides and apoC-III, respectively.
RESULTS
RESULTS
There were 20 participants (16 active:4 placebo) in the SAD part of the study, and 8 participants (6 active:2 placebo) in the MD part of the study. For the primary endpoint, no serious adverse events or clinically relevant laboratory abnormalities were reported. The majority of olezarsen plasma exposure occurred within 24 h post-dose. In the SAD cohorts at Day 15 the percentage reduction in apoC-III/TG was - 39.4%/ - 17.8%, - 60.8%/ - 52.7%, and - 68.1%/ - 39.2% in the 30, 60 and 90 mg doses, respectively, vs 2.3%/44.5% increases in placebo. In the MD cohort, at Day 92 the percentage reduction in apoC-III/TG was - 81.6/ - 73.8% vs - 17.2/ - 40.8% reduction in placebo. Favorable changes were also present in VLDL-C, apoB and HDL-C.
CONCLUSIONS
CONCLUSIONS
Single- and multiple-dose administration of olezarsen was safe, was well tolerated, and significantly reduced apoC-III and triglyceride levels in healthy Japanese Americans.
Identifiants
pubmed: 39363329
doi: 10.1186/s12944-024-02297-5
pii: 10.1186/s12944-024-02297-5
doi:
Substances chimiques
Apolipoprotein C-III
0
Triglycerides
0
Oligonucleotides
0
Oligonucleotides, Antisense
0
Types de publication
Journal Article
Randomized Controlled Trial
Clinical Trial, Phase I
Langues
eng
Sous-ensembles de citation
IM
Pagination
329Informations de copyright
© 2024. The Author(s).
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