PENTA 18 (Koncert)

19

Apr, 2015

Once vs. twice-daily lopinavir/ritonavir in HIV-1-infected children.

 

Authors: Paediatric European Network for Treatment of AIDS (PENTA).

Published in: AIDS 2015. 29(18):2447-2457

Objective To evaluate whether once daily (q.d.) lopinavir/ritonavir is noninferior to twice daily (b.i.d.) dosing in children.

Design International, multicentre, phase II/III, randomized, open-label, noninferiority trial (KONCERT/PENTA18/ANRS150).

Setting Clinical centres participating in the PENTA, HIV-NAT and PHPT networks.

Participants Children/adolescents with HIV-1 RNA viral load less than 50 copies/ml for at least 24 weeks on lopinavir/ritonavir-containing antiretroviral therapy.

Intervention Children were randomized to continue lopinavir/ritonavir b.i.d. or change to q.d.

Main Outcome Measure Confirmed viral load ≥50 copies/ml by 48 weeks (12% noninferiority margin).

Results One hundred seventy-three children were randomized in the KONCERT trial (86 q.d., 87 b.i.d.); 46% men, median (IQR) age 11 (9-14) years, CD4% 33 (27-38)%. By week 48, 97 and 98% of time was spent on q.d. and b.i.d., respectively (one q.d. child lost at week 4). Twelve q.d. vs. seven b.i.d. children had confirmed viral load ≥50 copies/ml within 48 weeks; estimated difference in percentage with viral load rebound 6% [90% CI (-2, 14)]. Numbers of children with grade 3/4 adverse events (11 vs. 7) or major resistance mutations (3 vs. 2) were similar, q.d. vs. b.i.d. (both P > 0.3). Among 26 children in an intrasubject lopinavir/ritonavir pharmacokinetic substudy, lower daily exposure (AUC0-24 161 h.mg/l vs. 224 h.mg/l) and lower Clast (1.03 mg/l vs. 5.69 mg/l) were observed with q.d. vs. b.i.d. dosing.

Conclusion Noninferiority for viral load suppression on q.d. vs. b.i.d. lopinavir/ritonavir was not demonstrated. Although results, therefore, do not support routine use of q.d. lopinavir/ritonavir, lack of safety concerns or resistance suggest that q.d. dosing remains an option in selected, adherent children, with close viral load monitoring.

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10

Apr, 2014

Pharmacokinetics of Pediatric Lopinavir/Ritonavir Tablets in Children When Administered Twice Daily According to FDA weight bands.

 

Authors: Bastiaans DE, Forcat S, Lyall H, et al.

Published in: Pediatr Infect Dis J. 2014;33(3):301-305

Background Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval and only body surface area by the EMA. This can lead to a different recommended dose. In addition, weight band–based dosing has not been formally studied in the target population. We evaluated the pharmacokinetics (PK) of LPV/r in children, administered twice daily according to the FDA weight bands, using pediatric tablets.

Methods Fifty-three HIV-infected children were included in the PK substudy of the Paediatric European Network for the Treatment of AIDS 18 trial (KONCERT). In this study, children were randomized to receive LPV/r twice or once daily, according to FDA weight bands. A PK assessment was performed in 17, 16 and 20 children in the 15–25 kg, ≥25–35 kg and >35 kg weight band, respectively, while children took the tablets twice daily. Rich sampling was performed, and PK parameters were calculated by noncompartmental analysis. Given the high percentage of Asian children, it was also tested whether there was a difference in PK parameters between Asian and non-Asian children.

Results For the total group, LPV geometric mean AUC0–12, Cmax and C12 were 106.9 h × mg/L, 12.0 mg/L and 4.9 mg/L, respectively. There were no significant differences in LPV PK parameters between the weight bands. In addition, weight was not found to be associated with variability in Cmax, C12 or AUC0–12 for the LPV PK parameters.

Conclusions FDA weight band–based dosing recommendations provide adequate exposure to LPV when using LPV/r pediatric tablets.

19

May, 2013

Pharmacokinetics of paediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands.

 

Authors: D Bastiaans, S Forcat, H Lyall, T Cressey, S Chalermpantmetagul, Y Saïdi, C Koenigs,  D Nayagam, A Compagnucci, S Montero, L Harper, C Giaquinto, E Colbers, D Burger.

Published in: 31st Annual Meeting of the ESPID- May 28 – June 1, 2013, Milan: Poster discussion Abstract A-534-0018-00429. 

19

Jul, 2012

Pharmacokinetics of 100/25 mg lopinavir/ritonavir tablets in children when dosed twice daily according to FDA weight bands.

 

Authors: Bastiaans DET, Forcat S, Lyall HEG, Cressey TR, Chalermpantmetagul S, Saïdi Y, Noguera T, Fortuny C, Compagnucci A, Bleier J, Giaquinto C, Colbers EP, Burger DM.

Published in: 4th International Workshop on HIV pediatrics 2012. July 20-21, 2012. L’Enfant Plaza Hotel, Washington DC, USA. 4th International Workshop on HIV pediatrics. July 20-21, 2012. L’Enfant Plaza Hotel, Washington DC, USA.

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19

Apr, 2012

Pharmacokinetics of 100/25 mg lopinavir/ritonavir tablets in children when dosed twice daily according to FDA weightbands.

 

Authors: D Bastiaans, S. Forcat, H.E.G. Lyall, T.R. Cressey, S. Chalermpantmetagul, Y. Saïdi, H.J. Scherpbier, A. Warris, A. Compagnucci, C. Giaquinto, E.P. Colbers, D.M. Burger on behalf of PENTA KONCERT Study Group.

Published in: 6th Netherlands Conference on HIV Pathogenesis, Prevention and Treatment. November 27, 2012.