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WEPDB0101

DIONE – 24 week efficacy, safety, tolerability and pharmacokinetics of DRV/r QD in treatment-naïve adolescents, 12 to <18 years.

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WEPDB0101

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  1. DIONE – 24 week efficacy, safety, tolerability and pharmacokinetics of DRV/r QD in treatment-naïve adolescents, 12 to <18 years • DRV/r is approved for the treatment of ARV-naïve (QD and BID) and experienced HIV-1-infected adults (BID), and in ARV-experienced pediatric patients aged 6 to <18 years (BID) • DIONE is a Phase II, 48-week, open-label trial of once-daily DRV/r 800/100mg in combination with ZDV/3TC or ABC/3TC • Enrollment • 12 patients, mean age 14.6 years, eight female, mean log10 HIV RNA of 4.72 copies/mL and CD4 cell count of 282 cells/mm3/18.3% • six received ZDV/3TC and six ABC/3TC • five infected via MTCT and three via heterosexual contact • Inclusion criteria • Treatment-naïve adolescents, 12–<18 yrs • Weight 40kg • HIV-1 RNA 1000 copies/mL Primary analysis at Week 24DRV/r 800/100mg qd + ZDV/3TC or ABC/3TC (site investigator-selected background regimen) DRV/r = darunavir/ritonavir; ARV = antiretroviral; ZDV = zidovudine3TC = lamivudine; ABC = abacavir; MTCT = mother-to-child transmission WEPDB0101

  2. Efficacy and safety findings 100 200 • 11/12 (92%) patients achieved HIV-1 RNA <50 copies/mL (ITT-TLOVR) • 12/12 (100%) by FDA snapshot algorithm • One patient with one DRV RAM (V11I) at baseline was a responder at Week 24 92% 175 80 150 Response (± SE): HIV-1 RNA <50 copies/mL(ITT-TLOVR; %) 60 Mean (± SE) change in CD4 cell count (cells/mm3) (NC=F) 100 40 DRV/r (N=12) DRV/r (N=12) 50 20 0 0 BAS 2 4 8 16 24 BAS 2 4 8 16 24 Time (weeks) Time (weeks) • Mean CD4 cell count increased by175 cells/mm3 • Two patients reported AEs at least possibly related to treatment (all grade 1 or 2) • No patient discontinued DRV/r due to an AE • No deaths SE = standard error; ITT = intent-to-treat; TLOVR = time-to-loss of virological response; NC=F = non-completer=failureFDA = Food and Drug Administration; RAM = resistance-associated mutation; AEs = adverse events WEPDB0101

  3. Pharmacokinetics • Rich sampling over24 hours after 2 weeksof dosing • Grey dotted line represents 130%, 100% and 80% (from top to bottom) of mean observed in adults in ARTEMIS1 Median: 87.9µg•h/mL Median: 2,196ng/mL 140 4,000 120 100 3,000 80 C0h(ng/mL) AUC (µg•h/mL) 2,000 60 40 1,000 20 0 0 AUC C0h • DRV exposure similar to adults receiving DRV/r 800/100mg QD1 • All had DRV C0h above EC50 for wild-type HIV (55ng/mL) • Conclusions • Over 24 weeks, once-daily DRV/r 800/100mg (with two NRTIs) was effective and well tolerated in ARV-naïve adolescents aged 12 to <18 years • No new safety concerns were identified • These findings support the use of once-daily DRV/r in treatment-naïve, adolescent HIV-1-infected patients 1. Sekar V, et al. 9th IWCPHIV 2008. Abstract P42AUC = area under the concentration-time curve; C0h = predose concentration; EC50 = effective concentration WEPDB0101

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