Treatment with Volanesorsen, a 2'-O-Methoxyethyl-Modified Antisense Oligonucleotide Targeting
| Autor: | Lynnetta M, Watts, Ewa, Karwatowska-Prokopczuk, Eunju, Hurh, Veronica J, Alexander, Kristin, Balogh, Louis, O'Dea, Richard S, Geary, Sotirios, Tsimikas |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Hypertriglyceridemia Male antisense oligonucleotide Apolipoprotein C-III Dose-Response Relationship Drug Drug-Related Side Effects and Adverse Reactions Moxifloxacin Oligonucleotides QTc interval subcutaneous (SC) therapeutic dose Oligonucleotides Antisense Placebo Effect Original Papers Healthy Volunteers Electrocardiography Double-Blind Method Humans Female volanesorsen RNA Messenger Triglycerides supratherapeutic dose |
| Zdroj: | Nucleic Acid Therapeutics |
| ISSN: | 2159-3345 |
| Popis: | The aim of this study was to assess the effect of volanesorsen on the corrected QT (QTc) interval. This thorough QT study enrolled 52 healthy male and female subjects who were randomized at a single site in a four-way crossover study. Subjects were randomly assigned to 1 of 12 treatment sequences and crossed over into four treatment periods over the course of which each subject was to receive a single therapeutic dose of volanesorsen as a 300 mg subcutaneous (SC) injection, a single supratherapeutic dose of volanesorsen as 300 mg intravenous (IV) infusion, a single oral (PO) dose of moxifloxacin (positive control), and placebo dose. The study demonstrated that volanesorsen 300 mg SC and 300 mg IV did not have a clinically relevant effect on ΔΔQTcF exceeding 10 ms. The largest mean effect at any postdose time point was 3.0 ms (90% confidence interval [CI]: 0.8–5.2) after SC dosing and 1.8 ms (90% CI −0.4 to 4.0) after IV dosing. Volanesorsen, at the studied therapeutic and supratherapeutic doses, does not have a clinically meaningful effect on the QTc. |
| Databáze: | OpenAIRE |
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