tetano
Editor, Senior Moderator
Br J Clin Pharmacol. 2017 Sep 20. doi: 10.1111/bcp.13405. [Epub ahead of print]
[h=1]Safety, Tolerability, and Pharmacokinetics of Radavirsen (AVI-7100), an Antisense Oligonucleotide Targeting Influenza A M1/M2 translation.[/h] Beigel JH[SUP]1[/SUP], Voell J[SUP]2[/SUP], Mu?oz P[SUP]2[/SUP], Kumar P[SUP]3[/SUP], Brooks KM[SUP]3[/SUP], Zhang J[SUP]4[/SUP], Iversen P[SUP]4,[/SUP][SUP]5[/SUP], Heald A[SUP]4,[/SUP][SUP]6[/SUP], Wong M[SUP]4,[/SUP][SUP]7[/SUP], Davey RT[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]AIMS:[/h] To assess the safety, tolerability, and pharmacokinetics (PK) of radavirsen following single ascending doses and multiple doses given as IV infusions in healthy adults.
[h=4]METHODS:[/h] A Phase 1 safety and pharmacokinetic (PK) study of radavirsen was performed in healthy volunteers. The study was divided into 2 parts. The first was a single-ascending dose study of 5 cohorts of 8 subjects each, randomized 6:2 to receive single intravenous doses of radavirsen ranging from 0.5 to 8 mg/kg or placebo. The second was a multiple dose study of 16 subjects randomized 12:4 to receive 8 mg/kg or placebo once daily for 5 days.
[h=4]RESULTS:[/h] 66 subjects were screened and 56 subjects were dosed between 2013 and 2015. At least one adverse event occurred in 31/42 (74%) who received radavirsen, and 13/14 (93%) receiving placebo. The most common adverse events were headache and proteinuria, and were similar among those receiving radavirsen or placebo. Single dose PK demonstrated relatively linear and dose-proportional increases in maximal concentration and area-under-the-concentration-time curve (AUC[SUB]0-24[/SUB] ). At 8 mg/kg in the multiple dose cohort, the Day 4 geometric mean AUC[SUB]0-24[/SUB] was 57.9 μg*h/mL.
[h=4]CONCLUSION:[/h] Single infusions of radavirsen up to 8 mg/kg, and multi-dosing at 8 mg/kg once daily for 5 days, appear to be safe and well-tolerated in healthy subjects. The multi-dose Day 4 AUC[SUB]0-24[/SUB] this study is comparable to the AUC which was associated with protection from viral infection in a preclinical ferret influenza model. Further evaluation of radavirsen for the treatment of influenza infections is warranted.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] antiviral; phosphorodiamidate morpholino oligomer; therapeutic
PMID: 28929521 DOI: 10.1111/bcp.13405
[h=1]Safety, Tolerability, and Pharmacokinetics of Radavirsen (AVI-7100), an Antisense Oligonucleotide Targeting Influenza A M1/M2 translation.[/h] Beigel JH[SUP]1[/SUP], Voell J[SUP]2[/SUP], Mu?oz P[SUP]2[/SUP], Kumar P[SUP]3[/SUP], Brooks KM[SUP]3[/SUP], Zhang J[SUP]4[/SUP], Iversen P[SUP]4,[/SUP][SUP]5[/SUP], Heald A[SUP]4,[/SUP][SUP]6[/SUP], Wong M[SUP]4,[/SUP][SUP]7[/SUP], Davey RT[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]AIMS:[/h] To assess the safety, tolerability, and pharmacokinetics (PK) of radavirsen following single ascending doses and multiple doses given as IV infusions in healthy adults.
[h=4]METHODS:[/h] A Phase 1 safety and pharmacokinetic (PK) study of radavirsen was performed in healthy volunteers. The study was divided into 2 parts. The first was a single-ascending dose study of 5 cohorts of 8 subjects each, randomized 6:2 to receive single intravenous doses of radavirsen ranging from 0.5 to 8 mg/kg or placebo. The second was a multiple dose study of 16 subjects randomized 12:4 to receive 8 mg/kg or placebo once daily for 5 days.
[h=4]RESULTS:[/h] 66 subjects were screened and 56 subjects were dosed between 2013 and 2015. At least one adverse event occurred in 31/42 (74%) who received radavirsen, and 13/14 (93%) receiving placebo. The most common adverse events were headache and proteinuria, and were similar among those receiving radavirsen or placebo. Single dose PK demonstrated relatively linear and dose-proportional increases in maximal concentration and area-under-the-concentration-time curve (AUC[SUB]0-24[/SUB] ). At 8 mg/kg in the multiple dose cohort, the Day 4 geometric mean AUC[SUB]0-24[/SUB] was 57.9 μg*h/mL.
[h=4]CONCLUSION:[/h] Single infusions of radavirsen up to 8 mg/kg, and multi-dosing at 8 mg/kg once daily for 5 days, appear to be safe and well-tolerated in healthy subjects. The multi-dose Day 4 AUC[SUB]0-24[/SUB] this study is comparable to the AUC which was associated with protection from viral infection in a preclinical ferret influenza model. Further evaluation of radavirsen for the treatment of influenza infections is warranted.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] antiviral; phosphorodiamidate morpholino oligomer; therapeutic
PMID: 28929521 DOI: 10.1111/bcp.13405