 |
|
|
| |
TMC-114/r: 24 week efficacy & safety
|
| |
| |
"TMC114/r outperforms Investigator-Selcted PI(s) in 3-class-experienced patients: week 24 primary analysis of POWER 1 (TMC114-C213)
C Katlama et al, (Hopital Pitie-Salpetriere Paris, France)
At CROI 2005 a 24-week interim analysis of phase IIb studies were presented. POWER 1 and POWER 2 are phase IIb stdies conducted in the US and outside the US. Here is the full 24-week analysis of POWER 1. Later this year full 24-week analysis of POWER 2 will be presented.
The purpose of this study is to determine theefficacy of TMC114/ritonavir in 3-class experienced patients in a randomized, controlled, international, multi-center phase IIb efficacy/safety study.
Three-class experienced patients on a stable PI-regimen with VL>1,000 copies/ml were randomized to one of four TMC114/r doses, or investigator-selected PI(s). Patients received optimized background regimen (OBR) (>2 NRTIs with/without enfuvirtide (T20). All patients had >1 primary PI mutation. All analyses were intent-to-treat. This is the abstract in the program, and the oral presentation will be presented at the Late Breakers Session on the last day of the conference, and will contain additional information.
RESULTS
318 patients had received a mean of 4 prior PIs. Baseline values were comparable across all groups: mean VL was 4.48 log10 copies/ml and CD4 was 179 cells/mm3; 13%, 31%, and 56%, respectively had 1, 2, or >3 primary PI mutations.
--During study, 10% of TMC114/r patients discontinued vs 62% of controls (control discontinuations mainly occurred for virologic failure).
Efficacy data are presented for the TMC114/4 dose selected for treatment-experienced patients (600/100 mg bid, n=65), vs controls, n=63).
--At week 24, the mean CD4 increase from baseline was 124 cells/mm3 for TMC114/r vs 20 cells/mm3 for control (P<0.001).
--The primary endpoint of >1 log10 VL reduction from baseline was achieved in 77% of TMC114/r patients vs 25% for control (p<0.001).
--Mean VL decrease for TMC114/r was 2.03 vs 0.63 log10 copies/ml for control (p<0.001).
--VL <50 copies/ml occurred in 53% of TMC114/r patients vs 18% of controls (p<0.001).
--VL <50 copies/ml was achieved in 63% of the 19 TMC114/r patients who received T20 in their OBR (previously T20 naïve) vs 56% of the 34 TMC114/r patients who did not receive T20.
The authors concluded the magnitude of viral suppression achieved with TMC114/r in 3-class experienced patients was significantly greater than control PIs and similar to that seen in less experienced patients. An exceptional CD4 response was observed.
Safety data results were also reported. During the study 62% of controls discontinued, 54% for virologic failure, 6% for adverse events. Ten percent of TMC114/r patients discontinued, 5% for AEs. Incidence of serious AEs was equivalent for TMC114/r and control groups (14%). Most AEs and lab abnormalities were mild-to-moderate in severity with similar incidence across all groups.
600/100mg dose group; control group
Any AE: 92%; 94%
Anye grade 3-4 AE: 23%; 29%
Grade 2-4 triglycerides, total cholesterol: 12.3%, 10.8%; 28.6%, 1.6%
Grade 3-4 ALT (AST): 1.5%, 0; 3.2%, 4.8%
Safety profile in HCV/HBV-HIV coinfected patients (n=31/255) was comparable to the overall population.
The authors concluded that TMC114/r was well tolerated and adverse events incidence was not dose related. Incidence of AEs of all grades was similar for TMC114/r and controls. When corrected for drug exposure, incidence of most common AEs was lower than for controls.
|
|
| |
|
|
|
|
|
