Effects of standard and supratherapeutic doses of nelfinavir on cardiac repolarization: a thorough QT study.

This was a randomized, 4-way crossover, third-party-blinded study in 68 healthy subjects to assess the effect of nelfinavir on QTc interval. Treatments included (A) nelfinavir 1250 mg every 12 hours on days 1-4, (B) nelfinavir 1250 mg every 12 hours on days 1-3 plus 3125 mg on day 4, (C) placebo, and (D) moxifloxacin 400 mg every 24 hours on days 1-4. Pharmacokinetics and triplicate 12-lead electrocardiograms were performed over 12 hours on days 1 and 4. Time-matched, placebo-subtracted, baseline-adjusted changes in QT intervals with Fridericia's (QTcF) correction were determined following nelfinavir and moxifloxacin administration. Neither dose of nelfinavir had a clinically relevant effect on the QTcF interval on day 4 (primary endpoint) and day 1 because at every time point the upper 90% confidence limit was below 10 milliseconds and, furthermore, the mean difference was below 5 milliseconds. Additionally, there was no clinically relevant effect on QTcB (Bazett's correction), uncorrected QT, or the RR interval on days 1 or 4. Pharmacokinetics confirmed adequate systemic exposure to nelfinavir and moxifloxacin. While nelfinavir exposure was higher in poor compared with extensive metabolizers of CYP2C19 isozyme, there were no corresponding significant differences in QTcF change from placebo. At clinically relevant, doses nelfinavir is unlikely to cause QTc prolongation.

RCT Entities:   Population Interventions Outcomes