title: Thorough QT/QTc study of ritonavir-boosted saquinavir following multiple-dose administration of therapeutic and supratherapeutic doses in healthy participants.
abstract: 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.
authors.affiliation: Hoffmann–La Roche, Inc, Nutley, NJ, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Paul
authors.initials: P
authors.lastname: Jordan
authors.forename: Laura
authors.initials: L
authors.lastname: Cristea
authors.forename: Miklos
authors.initials: M
authors.lastname: Salgo
authors.forename: Rana
authors.initials: R
authors.lastname: Farha
authors.forename: Stanley
authors.initials: S
authors.lastname: Kolis
authors.forename: Lois S
authors.initials: LS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D001372:Aza Compounds / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D016018:Least-Squares Analysis; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000009:adverse effects; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D019258:Saquinavir / Q000008:administration & dosage / Q000009:adverse effects*; D016171:Torsades de Pointes / Q000139:chemically induced; D055815:Young Adult
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D017320:HIV Protease Inhibitors; D011804:Quinolines; D019258:Saquinavir; D019438:Ritonavir; D000077266:Moxifloxacin