Ledipasvir/Sofosbuvir versus Simeprevir
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Study Design
This was a phase 2, open label study investigating treatment-naïve hepatitis C genotype 1-infected patients without cirrhosis, treated with simeprevir/sofosbuvir/ledipasvir. The study investigated the drug interaction between simeprevir and ledipasvir. (n=40) patients total were randomized into two groups Group 1; containing n=20 patients received simeprevir 150mg and sofosbuvir 400mg QD from day 1-14 and then from day 15-70 patients received simeprevir 150mg and ledipasvir/sofosbuvir 90/400mg QD. Group 2; containing n=20 patients received ledipasvir/sofosbuvir 90/400mg QD from day 1-14 and then from day 15-56 received simeprevir 150mg and ledipasvir/sofosbuvir 90/400mg once daily. The plasma concentration versus time profiles of simeprevir in the presence or absence of ledipasvir were assessed, along with safety data up to day 28.
Study Results
Cmax and AUC for the simeprevir with versus without ledipasvir (group 1) was 2.45 and 3.13 fold higher respectively. While for ledipasvir with versus without simeprevir (group 2) was 1.60 and 1.70 fold higher respectively based on least squares means ratios.
Adverse events (AEs) occurred in 73% of patients; all grade 1 or 2 and most common was photosensitivity. No serious AEs resulting in treatment discontinuation were reported.
Study Conclusions
Per the authors, the combination of simeprevir and ledipasvir in the presence of sofosbuvir led to no clinically significant increase in ledipasvir, but a moderate increase in simeprevir plasma concentrations. That being said no dosage adjustments were recommended upon the conclusion of this study. Safety profile was similar to that of the single agents with photosensitivity reported most frequently.1
References
Bourgeois S, Horsmans Y, Nevans F, van Vlierberghe H, Moreno C, Beumont M. Pharmacokinetic interactions between simeprevir and ledipasvir in treatment-naïve hepatitis c virus genotype 1-infected patients without cirrhosis treated with a simeprevir/sofosbuvir/ledipasvir regim. Ilc: International Liver Conference. Barcelona, Spain. 2016; April 2016.
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