|
|
Abstract
No QT prolongation four nelfinavir clinical studies
E. Pun1, A. Petersen1, M. Thompson2, M. Nelson3, E. Daniels1
Background: QT prolongation has been linked to Torsade de Pointes and sudden death. QT interval data from 4 nelfinavir (NFV) studies is presented.
Methods: CGs were taken in study A4301014C (Ph1, MD PK) in normal healthy volunteers (NHV), at screening and day 14. In A4301010, an efficacy and safety study in 57 HIV+ subjects, time-matched ECGs and PK sampling were taken at day 0, 14, and week 24 post-dose. A4301009 (Ph1 SD 3X3 cross over study, n= 24 NHV) examined the effects on NFV PK and ECG/QT interval of different food regimens, ECGs were collected on day 1, 8, & 15 pre- and post-dose. In A4301014A, 21 HIV+ subjects switched from a NFV based regimen using 250 mg to one using 625mg to obtain the full steady state PK on 625 mg. ECGs were taken at screening, day 1, pre-dose, and day 14 post-dose. In AG1343-1260, a 48-week open label study of NFV-based HAART long- term responders (>72 weeks), entry and study end ECGs were taken. QTc assessments were based on Fridericia’s correction formula
Results: In A4301014C, mean changes from baseline in QTc at day 14 at Ctrough= 2.2 msec and Tmax= -2.4 msec. A4301010 showed that no patient had > 30-msec increase in QTc from baseline, and that the time-matched mean change from baseline in QTc was -3.8 msec The mean change in QTc from baseline to the last measured QTc was 2.9 msec. In A4301009, no subject experienced a concentration-related increase in QTc. Mean QTc change from A4301014A showed no substantial variation from baseline at day 1 or day 14 and no concentration-related increase in QTc. AG1343-1260 ECGs at baseline showed no instances of QTc prolongation.
Conclusions: Overall ECG experience in 4 NFV studies, 39 normal healthy volunteers and 136 HIV-infected subjects, showed no QTc prolongation effect.
AIDS 2006 - XVI International AIDS Conference
Abstract no.
CDB0143
Suggested Citation
"E.Pun, et al.
No QT prolongation four nelfinavir clinical studies.
:
AIDS 2006 - XVI International AIDS Conference:
Abstract no.
CDB0143"
|
|
|