Doravirine versus Ledipasvir/Sofosbuvir
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Study Design
This was an openlabel, single dose, 3-period randomized crossover study in 12 healthy males and 2 healthy females aged 25 to 60. Treatments were a single dose of 100 mg doravirine, a single dose of 90 mg ledipasvir/400 mg sofosbuvir, or all three drugs coadministered. Plasma PK samples were collected for evaluation of doravirine, ledipasvir, sofosbuvir and its metabolite GS 331007. A linear mixed-effects model was used for the analysis of the natural log (ln)-transformed AUC0-inf, Cmax, and C24 and evaluated separately using a linear mixed effects model with fixed effects terms for treatment and period. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the treatment measurements within each subject.
Study Results
The PK of all four analytes was not meaningfully altered by coadministration of doravirine with ledipasvir/sofosbuvir. For the comparison of (doravirine + ledipasvir/ sofosbuvir) / (ledipasvir/sofosbuvir alone), the geometric mean ratios (GMRs) (90% confidence intervals (CIs)) for ledipasvir AUC0-inf and Cmax were 0.92 (0.80, 1.06) and 0.91 (0.80, 1.02), respectively; for sofosbuvir the GMRs (90% CI) for AUC0-inf and Cmax were 1.04 (0.91, 1.18) and 0.89 (0.79, 1.00), respectively; and for GS- 331007, the GMRs (90% CI) for AUC0-inf and Cmax were 1.03 (0.98, 1.09) and 1.03 (0.97, 1.09), respectively. For the comparison of (doravirine + ledipasvir/sofosbuvir) / (doravirine alone), the GMRs (90% CIs) for doravirine AUC0-inf, Cmax, and C24 were 1.15 (1.07, 1.24), 1.11 (0.97, 1.27), and 1.24 (1.13, 1.36), respectively. Six subjects (43%) reported ≥1 AE during treatment. Coadministration of all three drugs was generally well tolerated.
Study Conclusions
The author’s concluded that there was no meaningful effect on doravirine, ledipasvir, sofosbuvir or GS-
331007 PK when doravirine and ledipasvir/ sofosbuvir were coadministered. The results of this study suggest that doravirine and ledipasvir/sofosbuvir may be co-administered in patients coinfected with HIV and HCV without dose adjustment.
References
Ankrom W, Yee K, Triantafyllou I, Fan L, Sanchez R, Khalilieh S. Doravirine does not have a clinically meaningful pharmacokinetic interaction with ledipasvir/sofosbuvir (harvoni®) . International Workshop On Clinical Pharmacology Of Antiviral Therapy. Chicago, IL, USA. 18; June 2017.
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