![](images/null.gif) |
![](images/null.gif) |
![](images/null.gif) |
|
Safety and Antiviral Activity of NS5B Polymerase Inhibitor MK-3281in Genotype 1 and 3 HCV-Infected Patients
|
|
|
Reported by Jules Levin
AASLD Nov 3 2009, Boston, MA
DM Brainard,1 MS Anderson,1 AS Petry,1 K Van Dyck,1 I De Lepeleire,1
K Sneddon,1 CE Cummings,1 RB Nachbar,1 RJO Barnard,1 P Sun,1 P Panorchan,1 E Udezue,2 B Sanderson,3 F Wagner,4M Iwamoto,1 JA Chodakewitz,1 JA Wagner1
1Merck & Co., Inc. Whitehouse Station, NJ; 2Chiltern Place, Slough, England; 3Chiltern (Early Phase) Limited, Dundee, Scotland; and 4Charite University Hospital, Berlin, Germany
![caption.gif](../images/corrections/caption.gif)
![image002.gif](../images/110509/110509-9/image002.gif)
Background
MK-3281 is a tetracyclic indole non-nucleoside hepatitis C virus · (HCV) NS5B polymerase inhibitor that binds in the thumb region and inhibits the enzyme prior to elongation.
MK-3281 demonstrates robust in vitro potency against genotypes
(GT) 1a/b and 3 HCV.
- EC50 GT1a (H77) in 10% FCS = 12 nM
- EC50 GT1b (con1) in 10% FCS = 41 nM
- EC50 GT3a in 10% FCS = 37 nM
MK-3281 exhibits >1000-fold selectivity over the human DNA · polymerases α, β, λ (IC50 >50 µM).
MK-3281 has been generally safe and well tolerated in healthy · male volunteers dosed for up to 10 days.1
Study Objectives
Evaluate the safety and tolerability of MK-3281 administered for 7 days to male patients infected with HCV genotypes 1 and 3.
Evaluate the pharmacokinetic profile of MK-3281 (e.g., AUC0-12hr, Cmax, C12hr, Tmax, apparent t1/2 and accumulation ratios) with multiple dose administration.
Evaluate the antiviral activity of MK-3281 administered as monotherapy for 7 days to male patients infected with HCV genotype 1 or 3.
![image004.gif](../images/110509/110509-9/image004.gif)
![image006.gif](../images/110509/110509-9/image006.gif)
RESULTS
![image008.gif](../images/110509/110509-9/image008.gif)
![image010.gif](../images/110509/110509-9/image010.gif)
![image012.gif](../images/110509/110509-9/image012.gif)
![image014.gif](../images/110509/110509-9/image014.gif)
![image016.gif](../images/110509/110509-9/image016.gif)
![image018.gif](../images/110509/110509-9/image018.gif)
![image020.gif](../images/110509/110509-9/image020.gif)
![image022.gif](../images/110509/110509-9/image022.gif)
![image024.gif](../images/110509/110509-9/image024.gif)
![image026.gif](../images/110509/110509-9/image026.gif)
![image028.gif](../images/110509/110509-9/image028.gif)
![image030.gif](../images/110509/110509-9/image030.gif)
![image032.gif](../images/110509/110509-9/image032.gif)
![image034.gif](../images/110509/110509-9/image034.gif)
|
|
|
![](images/null.gif) |
![](images/null.gif) |
|
|