144LB
48-Week Primary Analysis of Trial TMC278-C204: TMC278 Demonstrates Potent and Sustained Efficacy in ART-naïve Patients
Anton Pozniak*1, J Morales-Ramirez2, L Mohapi3, M Santoscoy4, P Chetchotisakd5, M Hereygers6, S Vanveggel6, M Peeters6, B Woodfall6, and K Boven7
1Chelsea and Westminster Hosp, London, UK; 2Clinical Res, San Juan, Puerto Rico; 3Univ of the Witwatersrand, Johannesburg, South Africa; 4Hosp Gabriel Mancera IMSS, Mexico City, Mexico; 5Srinagarind Hosp, Khon Kaen, Thailand; 6Tibotec BVBA, Mechelen, Belgium; and 7Tibotec Inc, Yardley, PA, US
Background: TMC278, a new diarylpyrimidine non-nucleoside reverse
transcriptase inhibitor (NNRTI), is highly active against wild type and
drug-resistant HIV-1 in vitro and has
demonstrated potent short-term antiviral activity in patients.
Methods: TMC278-C204 is an ongoing, randomized, active-controlled,
partially blinded phase IIb dose-finding trial to evaluate the efficacy and
safety of 3 blinded, once-daily doses of TMC278 compared with open-label
efavirenz (EFV), all in combination with Combivir or Truvada, in ART-naïve
HIV-1-infected patients. The primary objective is to select a TMC278 dose for
further development. The primary endpoint was the proportion of patients with
confirmed viral load <50 copies/mL (TLOVR definition, non-completer = failure)
at 48 weeks.
Results: We randomized 368 patients (33% female) to TMC278 25, 75, or 150 mg once daily,
or EFV 600 mg once daily. Combivir was used by 76% of patients and Truvada by
24%. Baseline median log10 viral load was 4.85
copies/mL and median CD4 cell count was 203 cells/mm3;
48-week results for the intent-to-treat population (TLOVR) are shown in the
table. There was no statistically significant difference in the efficacy
results between any of the treatment arms. The most common adverse events were
nausea (TMC278 doses combined 35% vs EFV 29%) and headache (18% vs 16%).
Nervous system disorders and psychiatric events were less frequent with TMC278
(28% and 13%, respectively) compared with EFV (48% and 16%, respectively). Rash
events were also less frequent for TMC278 (8%) vs EFV (19%). Mean (SD) changes
from baseline of total and LDL cholesterol were 5 mg/dL (30) and 0 mg/dL (24)
with TMC278 versus 31 mg/dL (30) and 16 mg/dL (26), respectively with EFV. In
patients treated with Combivir, anemia, or neutropenia led to switches off
zidovudine (AZT) in 6% of TMC278 subjects and 1% of EFV subjects. For TMC278
and EFV, respectively, the incidence of grade 3 or 4 adverse events was 25% vs
16%; serious adverse events was 10% vs 9%; and grade 3 or 4 lab abnormalities
was 22% vs 20%.
Conclusions: All doses of TMC278 demonstrated significant and sustained efficacy
similar to that of EFV over 48 weeks in ART-naïve patients. TMC278 was
generally well tolerated with lower nervous system, rash, and lipid effects
than EFV.
|
