1GlaxoSmithKline, Research Triangle Park, NC, USA firstname.lastname@example.org.
2Pharstat, Research Triangle Park, NC, USA.
3PAREXEL, Baltimore, MD, USA.
4GlaxoSmithKline, Research Triangle Park, NC, USA.
Eltrombopag is an orally bioavailable thrombopoietin receptor agonist approved for the treatment of thrombocytopenia associated with chronic immune (idiopathic) thrombocytopenic purpura and chronic hepatitis C virus (HCV) infection. This study evaluated the potential drug-drug interaction between eltrombopag and the HCV protease inhibitors boceprevir and telaprevir. In this open-label, 3-period, single-sequence, crossover study, 56 healthy adult subjects were randomized 1:1 to cohort 1 (boceprevir) or cohort 2 (telaprevir). Dosing in period 1: single 200-mg dose of eltrombopag; period 2: boceprevir 800 mg or telaprevir 750 mg Q8h for 10 days; period 3: single 200-mg dose of eltrombopag with either boceprevir 800 mg or telaprevir 750 mg Q8h (3 doses). All doses were administered with food; eltrombopag was administered with low-calcium food. There was a 3-day washout between periods 1-2 and no washout between periods 2-3. Serial pharmacokinetic samples were collected during 72 h in periods 1 and 3 and during 8 h in period 2. Coadministration of eltrombopag increased the rate of boceprevir absorption, resulting in a 1-h earlier boceprevir Tmax, 20% increase in Cmax, 32% decrease in Cτ, and no change in AUC0-τ. Coadministration of eltrombopag did not alter telaprevir pharmacokinetics. Coadministration of boceprevir or telaprevir did not alter eltrombopag pharmacokinetics. Dysgeusia, headache, and somnolence occurred in ≥2 subjects. One subject withdrew because of nausea, headache, dizziness, sinus pressure, and vomiting. There were no severe or serious adverse events. Dose adjustment is not required when eltrombopag is coadministered with boceprevir or telaprevir given lack of clinically significant pharmacokinetic interaction.