Table 9.

Simeprevir

Ref.	n	Design	Treatment	Population	Outcome
Fried et al[80]	338	Phase 2b double blind, placebo controlled randomized clinical trial	Simeprevir PEGIFN-α-2a/RBV	Treatment-naıve patients with HCV genotype 1 infection.	Simeprevir in combination with PEGIFN/RBV significantly improved SVR rates and shortened therapy duration. Depression occurred in 10.4% of patients on simeprevir and 18.2% on standard treatment
Zeuzem et al[79]	396	Placebo controlled, randomized clinical trial	Simeprevir, PEGIFN-α-2a/RBV	patients with HCV genotype-1 infection previously treated with PEGIFN/RBV	12, 24, or 48 wk simeprevir with 48 wk PEGIFN/RBV significantly increased rates of SVR and was generally well tolerated. Depression occurred in 2/396 simeprevir patients
Jacobson et al[81]	394	Phase 3, randomized, double blind, placebo controlled multicenter clinical trial	Simeprevir, PEGIFN-α-2a/RBV	Treatment naïve patients with HCV genotype 1	Simeprevir with PEGIFN-α-2a/RBV shortens therapy without worsening the adverse event profiles associated with PEGIFN
Manns et al[82]	257	Phase 3 multicenter randomized, placebo controlled clinical trial	Simeprevir PEGIFN-α-2a or 2b/RBV	Treatment-naive patients with HCV genotype 1 infection	Addition of simeprevir to PEGIFN-α-2a or PEGIFN-α-2b plus RBV improved SVR without worsening the known adverse events associated with peginterferon
Kumada et al[83]	79	Open label non comparative multicenter trial	Simeprevir PEGIFN-α-2b/RBV	HCV genotype 1 - treatment-naïve or had previously received IFN-based therapy	Simeprevir combined with PEGIFN-α-2b/RBV was effective across both groups. One patient in the control group receiving standard therapy alone discontinued due to grade 2 depression

PEGIFN: Pegylated interferon (peginterferon); RBV: Ribavirin; HCV: Hepatitis C virus; SVR: Sustained virologic response; IFN: Interferon.