105aLB
Results of BENCHMRK-1, a Phase III Study Evaluating the Efficacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-class Resistant Virus
David Cooper*1, J Gatell2, J Rockstroh3, C Katlama4, P Yeni5, A Lazzarin6, J Chen7, R Isaacs7, H Teppler7, B Nguyen7, and for the BENCHMRK-1 Study Group
1Univ of New South Wales, Sydney, Australia; 2Univ of Barcelona, Spain; 3Univ of Bonn, Germany; 4Hosp Pitie Salpetriere, Paris, France; 5Hosp Bichat Claude Bernard, Paris, France; 6San Raffaele Sci Inst, Milan, Italy; and 7Merck Res Labs, West Point, PA, US
Background: MK-0518 is a novel
and potent HIV-1 integrase inhibitor, which has no cross resistance to
currently approved antiretroviral drugs.
Methods: BENCHMRK-1
(Protocol 018) is an ongoing multi-center,
triple-blind randomized study to evaluate safety and efficacy of oral MK-0518
400 mg twice daily vs placebo (2 : 1 randomization), each plus optimized
background therapy (OBT), in HIV-infected patients failing ART with HIV
resistant to 3 classes of oral ART. Patients were enrolled in Europe, Asia and
the Pacific, and Peru.
Efficacy endpoints included percentage of patients with HIV RNA <400 and
<50 copies/mL and change from baseline in CD4 cell counts.
Results: Pre-planned 16-week
analyses are summarized in the table. About 60% of patients have completed week
24; data from week 24 also demonstrate superior efficacy of MK-0518 over
placebo. MK-0518 was generally well tolerated with an adverse experience
profile similar to that of placebo.
Conclusions: In this
phase III study in patients failing ART with triple-class resistant HIV, oral
MK-0518 400 mg twice daily plus OBT demonstrated potent and superior
antiretroviral effect compared to placebo plus OBT at week 16 and 24, and was
generally well tolerated.
|
BENCHMRK-1
(Protocol 018)
|
MK-0518*
n = 232 patients
|
Placebo*
n = 118 patients
|
Difference
|
|
Baseline
Characteristics: Mean (SD)
|
|
|
|
|
HIV RNA (log10 copies/mL)
|
4.6
(0.8)
|
4.5
(0.8)
|
D MK-0518-Placebo1
|
|
CD4
Cell Count (cells/mm3)
|
156
(139)
|
153
(152)
|
|
|
Efficacy
at Week 16 (95% confidence intervals)
|
|
|
% HIV
RNA <400 copies/mL2
|
77
(71,83)
|
41
(32,50)
|
37
(26,47) %
|
|
% HIV RNA < 50 copies/mL2
|
61
(55,68)
|
33
(25,42)
|
28
(17,38) %
|
|
CD4
Change from Baseline§ (cells/mm3)
|
83 (
71,95)
|
31 (
18,45)
|
51
(33,70) %
|
|
*MK-0518
and placebo were given with OBT
1 Difference between MK-0518 and placebo; a positive value
indicates that MK-0518 was better than placebo
2 Non-completer = failure
§ Baseline values carried forward
for virologic failures
% Nominal p <0.001
|
|
