Antiviral activity of narlaprevir combined with ritonavir and peginterferon in chronic hepatitis C patients

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1002/hep.23899/abstract;jsessionid=97E5F15\

4BA2773299995CE9681A4EA08.d01t01

Viral Hepatitis

Antiviral activity of narlaprevir combined with ritonavir and peginterferon in

chronic hepatitis C patients

J. de Bruijne1,†,

J.F. Bergmann2,†,

H.W. Reesink1,*,‡,

C.J. Weegink1,

R. Molenkamp3,

J. Schinkel3,

X. Tong4,

J. Li4,

M.A. Treitel4,

E.A. 4,

J.J. van Lier5,

A.A. van Vliet5,

H.L.A. Janssen2,

R.J. de Knegt2

DOI: 10.1002/hep.23899

Copyright © 2010 American Association for the Study of Liver Diseases

Issue

Hepatology

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

Narlaprevir (SCH 900518) is a potent inhibitor of the HCV NS3 serine protease

that is primarily metabolized by the cytochrome P450-3A4 system (CYP3A4). In

order to explore the use of ritonavir-based pharmacokinetic enhancement of an

HCV protease inhibitor, this study investigated the safety, tolerability,

pharmacokinetics and antiviral activity of narlaprevir (with or without

ritonavir) administered as monotherapy and combination therapy with pegylated

interferon-α-2b to HCV genotype 1 infected patients. This was a randomized,

placebo-controlled, two period, blinded study in 40 HCV genotype 1 infected

patients (naïve and treatment-experienced). In Period 1, narlaprevir was

administered for 7 days as 800 mg TID without ritonavir or 400 mg BID with 200

mg ritonavir BID. In Period 2, after a 4 week washout, the same dose and regimen

of narlaprevir was administered in combination with pegylated interferon-α-2b

for 14 days. Upon completion of Period 2, all patients initiated pegylated

interferon-α-2b and ribavirin treatment. A rapid and persistent decline in

plasma HCV RNA was observed in both treatment-experienced and -naive patients

during Period 1, with a mean viral load decline of at least 4 log10 in all

treatment groups. A high percentage of both treatment-experienced (50% and 50%)

and naïve (75% and 63%) patients had undetectable HCV RNA (<25 IU/mL) after

Period 2. Standard of care resulted in SVR rates of 38% and 81% in

treatment-experienced and treatment–naïve patients, respectively. Narlaprevir

(with or without ritonavir) alone or in combination with pegylated

interferon-α-2b was safe and well tolerated.

Conclusion:

Narlaprevir administration resulted in a robust HCV RNA decline and high SVR

rates when followed by standard of care in both treatment-experienced and

treatment-naïve HCV genotype 1-infected patients. (HEPATOLOGY 2010.)

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1002/hep.23899/abstract;jsessionid=97E5F15\

4BA2773299995CE9681A4EA08.d01t01

Viral Hepatitis

Antiviral activity of narlaprevir combined with ritonavir and peginterferon in

chronic hepatitis C patients

J. de Bruijne1,†,

J.F. Bergmann2,†,

H.W. Reesink1,*,‡,

C.J. Weegink1,

R. Molenkamp3,

J. Schinkel3,

X. Tong4,

J. Li4,

M.A. Treitel4,

E.A. 4,

J.J. van Lier5,

A.A. van Vliet5,

H.L.A. Janssen2,

R.J. de Knegt2

DOI: 10.1002/hep.23899

Copyright © 2010 American Association for the Study of Liver Diseases

Issue

Hepatology

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

Narlaprevir (SCH 900518) is a potent inhibitor of the HCV NS3 serine protease

that is primarily metabolized by the cytochrome P450-3A4 system (CYP3A4). In

order to explore the use of ritonavir-based pharmacokinetic enhancement of an

HCV protease inhibitor, this study investigated the safety, tolerability,

pharmacokinetics and antiviral activity of narlaprevir (with or without

ritonavir) administered as monotherapy and combination therapy with pegylated

interferon-α-2b to HCV genotype 1 infected patients. This was a randomized,

placebo-controlled, two period, blinded study in 40 HCV genotype 1 infected

patients (naïve and treatment-experienced). In Period 1, narlaprevir was

administered for 7 days as 800 mg TID without ritonavir or 400 mg BID with 200

mg ritonavir BID. In Period 2, after a 4 week washout, the same dose and regimen

of narlaprevir was administered in combination with pegylated interferon-α-2b

for 14 days. Upon completion of Period 2, all patients initiated pegylated

interferon-α-2b and ribavirin treatment. A rapid and persistent decline in

plasma HCV RNA was observed in both treatment-experienced and -naive patients

during Period 1, with a mean viral load decline of at least 4 log10 in all

treatment groups. A high percentage of both treatment-experienced (50% and 50%)

and naïve (75% and 63%) patients had undetectable HCV RNA (<25 IU/mL) after

Period 2. Standard of care resulted in SVR rates of 38% and 81% in

treatment-experienced and treatment–naïve patients, respectively. Narlaprevir

(with or without ritonavir) alone or in combination with pegylated

interferon-α-2b was safe and well tolerated.

Conclusion:

Narlaprevir administration resulted in a robust HCV RNA decline and high SVR

rates when followed by standard of care in both treatment-experienced and

treatment-naïve HCV genotype 1-infected patients. (HEPATOLOGY 2010.)