Pharmacokineticpharmacodynamic analyses of 药动学药效学分析.pptxVIP

Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients aged 3 to 6 years: Week 48 analysis of the ARIEL trial Avy Violari,1 Rosa Bologna,2 Nagalingeswaran Kumarasamy,3 Jose Henrique Pilotto,4 Annemie Hendrickx,5 Thomas N Kakuda,6 Erkki Lathouwers,5 Magda Opsomer,5 Tom Van de Casteele5 and Frank L Tomaka6 1Chris Hani Baragwanath Hospital, Johannesburg, South Africa; 2Helios Salud, Buenos Aires, Argentina; 3YRGCARE Medical Centre, VHS, Chennai, India; 4Hospital Geral De Nova Iguacu, Rio De Janeiro, Brazil; 5Janssen Infectious Diseases BVBA, Beerse, Belgium; 6Janssen Research Development LLC, Titusville, NJ, USA Background 1. Violari A, et al. 18th CROI 2011. Abstract 713 DRV/r = darunavir/ritonavir*TMC114-TiDP29-C228; NCARIEL=dArunavir in tReatment experIenced pEdiatric popuLation DRV/r is approved for HIV-1-infected children and adolescents aged 3 to 18 years The primary 24 week analysis of ARIEL1,* led to the approval of DRV/r for treatment-experienced children aged 3 to 6 years weighing at least 10kg 48-week safety and efficacy outcomes from ARIEL are reported ARIEL: study design and objectives Phase II, open-label trial conducted in five countries* Primary objective Assess pharmacokinetics, short-term safety and efficacy to support dose recommendations of DRV/r by bodyweight in children Dosing Initial dose of DRV/r 20/3mg/kg bid DRV 100mg/mL oral suspension and ritonavir 80mg/mL solution After Week 2 analysis and Data Safety Monitoring Board recommendations 25/3mg/kg bid for patients weighing 10 to 15kg 375/50mg bid fixed for patients weighing 15 to 20kg 1. Johnson VA, et al. Top HIV Med 2009;17:138–45 Primary analysis at Week 24 ?Investigator-selected OBR of ≥2 allowed antiretrovirals Week 48 HAART = highly active antiretroviral therapyOBR = optimised background regimenRAM = resistance-associated mutation*Argentina, Brazil, India, Kenya, and South Africa ARIEL: baseline demographics and disease characterist