www.hivandmore. de Comparison of 48 week efficacy and safety of 400mg QD nevirapine (NVP) extended release formulation (Viramune XR) versus 200mg BID nevirapine immediate release formulation (Viramune IR) in combination with emtricitabine/tenofovir in antiretroviral (ARV) naïve HIV-1 infected patients (VERxVE) J. Gathe, JR. Bogner, S. Santiago, A. Horban, M. Nelson, P. Cahn, J. Andrade, D. Spencer, C. Yong, T. Nguyen, W. Zhang, M. Drulak and A. Quinson* *Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA
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Comparison of 48 week efficacy and safety of 400mg QD nevirapine (NVP) extended release formulation (Viramune XR) versus 200mg BID nevirapine immediate release formulation (Viramune IR) in combination with emtricitabine/tenofovir in antiretroviral (ARV) naïve HIV-1 infected patients (VERxVE)
J. Gathe, JR. Bogner, S. Santiago, A. Horban, M. Nelson, P. Cahn, J. Andrade, D. Spencer, C. Yong, T. Nguyen, W. Zhang,
M. Drulak and A. Quinson*
*Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA
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Viramune 200mg immediate release (IR) is a well established
component of effective antiretroviral therapy in HIV-1 infected
patients
Viramune 200mg IR plus emtricitabine/tenofovir (FTC/TDF) recently
demonstrated similar efficacy to atazanavir/ritonavir plus FTC/TDF,
with a more favourable lipid profile1
Viramune extended release formulation (Viramune XR) may
increase therapeutic benefit by improving compliance through once-
daily
(QD) dosing
1. Soriano V. et al. 2010 Manuscript submitted
VERX VE: Rationale for Viramune Extended Release (XR) Formulation
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Objective:
To evaluate the efficacy of Viramune XR 400 mg QD vs Viramune IR
200 mg BID, in ARV treatment-naïve, HIV–1-infected patients after
48 weeks of treatment
• Study design:
• Double-blind, double-dummy, non-inferiority study
• 1:1 randomization to Viramune XR or Viramune IR after 14-day
Viramune IR lead-in 200 mg QD dose (given to all patients)
VERX VE: Proportion with Virologic Response by Visit (VL <50 copies/mL, FAS)
FAS = Full analysis set
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• Designated trial centres participated in a pharmacokinetic sub-study, involving ~30 patients from each treatment arm
• Blood samples collected intensively for 24 hr following morning NVP administration in week 4 (visit 4): day 28
• Plasma NVP levels measured by tandem mass spectrometry (LC-MS/MS)
• Arithmetic mean (±SD) plasma concentration of NVP following 400mg QD and 200mg BID dosing determined
VERX VE: PK Sub-study at Day 28
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200 mg NVP IR bid (n=25)700
0
Time [hours]
Vir
am
une P
lasm
a (
ng/m
L)
6000
5000
4000
3000
2000
200 mg NVP XR qd (n=24)
0 4 8 12 16 20 24
(N=25)
(N=24)200mg Viramune IR BID400mg Viramune XR QD
VERX VE: PK Sub-study at Day 28: Results
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Parameter Viramune IR Viramune XR
Total number of patients, n/N 372/464 (80.2) 406/486 (83.5)
Geometric mean, trough ss (ng/mL), No. Responders/Total within stratum (n/N)
<1000 3/5 (60.0) 3/9 (33.3)
1000–<2000 25/31 (80.6) 46/54 (85.2)
2000–<3000 50/66 (75.8) 124/144 (86.6)
3000–<4000 108/125 (86.4) 71/90 (86.4)
≥4000 186/237 (78.5) 43/57 (80.3)
LLOQ (lower limit of quantification) = 50 copies/mL
Virologic response rates stratified by geometric mean steady state (ss) trough plasma concentrations (ng/mL)
FAS = Full analysis set
VERX VE: PK-PD Response Week 48 (FAS): Viramune XR Equivalent to Viramune IR at ≥1000ng/mL
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Change in median value from baseline at Week 48 (%)
Substrate
[mg/dL]
Viramune IR
(N=406)
Viramune XR
(N=419)
Triglycerides -8 (–9%) -6 (–7%)
Cholesterol 22 (13%) 19 (11%)
LDL-c 8 (9%) 7 (7%)
HDL-c 12 (32%) 10 (27%)
Total cholesterol/HDL-c -14% -12%
VERX VE: Percentage Change in Lipid Profile Viramune IR vs Viramune XR at Week 48
Viramune XR demonstrated a similar lipid friendly profile to that of Viramune IR
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*Investigator defined. Please note: No drug-related fatalities. Atherosclerosis/hypertension; tuberculosis (meningitis); two sepsis, myocardial infarction; respiratory alkalosis.
Parameter Viramune IR Viramune XR
Number of patients (N) 506 505
Any AE, n (%) 452 (89.3) 443 (87.7)
AEs leading to discontinuation, n (%)
45 (8.9) 32 (6.3)
Serious AEs, n (%) 54 (10.7) 58 (11.5)
Deaths 5 (1.0) 1 (0.2)
Drug-related* AEs 123 (24.3) 100 (19.8)
DAIDS Grade 3 or 4 AEs 91 (18.0) 73 (14.5)
DAIDS Grade 4 AEs 23 (4.5) 16 (3.2)
VERX VE: AE Summary Randomized Phase, FAS
FAS = Full analysis set
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Pivotal Trial (VERXVE) demonstrated: non-inferior efficacy for Viramune XR to Viramune IR similar safety and tolerability for both formulations; no new AEs
identified the combination of Viramune IR or Viramune XR with FTC/TDF is an
effective ARV treatment
PK – PD: Similar efficacy noted across many PK strata indicating adequate
trough drug exposure for Viramune XR Consistent relative trough exposure of Viramune XR to IR across
gender, region, and baseline viral-load strata
Once-daily dosing with VIRAMUNE XR provides patients with a more convenient treatment regimen with comparable efficacy and safety to VIRAMUNE IR
VERX VE: Conclusions
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Comparison of 48 week efficacy and safety of 400mg QD nevirapine extended release formulation (Viramune XR)
versus 200mg BID nevirapine immediate release formulation (Viramune IR) in combination with Truvada® in antiretroviral
(ARV) naïve HIV-1 infected patients (VERxVE)
J. Gathe, JR. Bogner, S. Santiago, A. Horban, M. Nelson, P. Cahn, J. Andrade, D. Spencer, C. Yong, T. Nguyen, W. Zhang,
M. Drulak and A. Quinson*
*Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA