Thorough QT/QTc Study of Ritonavir‐Boosted Saquinavir Following Multiple‐Dose Administration of Therapeutic and Supratherapeutic Doses in Healthy Participants

The effect of saquinavir‐boosted ritonavir at therapeutic (1000/100 mg twice daily [bid]) and supratherapeutic (1500/100 mg bid) doses was evaluated in a double‐blind, placebo‐ and positive‐controlled (moxifloxacin 400 mg) 4‐way crossover thorough QT/QTc study. Least squares mean estimated study‐specific QTc (QTcS) change from dense predose baseline (ddQTcS dense ) was the primary endpoint. Greatest mean increase in ddQTcS dense occurred 12 hours postdose for the 1000/100‐mg group (18.9 ms) and 20 hours for the 1500/10‐mg group (30.2 ms). The upper 1‐sided 95% confidence interval was >20 ms from 2 to 20 hours postdose in both groups. ddQTcB dense and ddQTcF dense were similar to ddQTcS dense . No QTcS, QTcF, or QTcB measurements were >500 ms. One participant receiving 1000/100 mg and 3 receiving 1500/100 mg had a maximum ddQTcS dense >60 ms. More participants with ≥1 adverse event received saquinavir/ritonavir. PubMed search and Roche postmarketing data did not reveal publications or reports directly presenting the effect of saquinavir on QT/QTc or causing torsade de pointes.