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Abstract
Pharmacokinetics and safety of tipranavir/ritonavir (TPV/r) alone or in combination with saquinavir (SQV), amprenavir (APV), or lopinavir (LPV): Interim analysis of BI1182.51
S Walmsley1, J Leith2, C Katlama3, K Arasteh4, G Pierone5, G Blick6, A Lazzarin7, M Johnson8, C Samuels9, P Jones9, R Chaves10, A Quinson11, V Kohlbrenner12, S McCallister12, D Mayers12, K Curry12
1University of Toronto, Toronto, Canada; 2Boehringer Ingelheim, Burlington, Canada; 3Hospital Pitie Salpetriere, Paris, France; 4Epimed GmbH, Berlin, Germany; 5Treasure Coast Infectious Disease Consultants, Vero Beach, FL, United States; 6Circle Medical, Norwalk, CT, United States; 7Fondazione Centro S Raffaele Del Monte Tabor, Milan, Italy; 8Royal Freel Hosp, London, United Kingdom; 9Boehringer Ingelheim, Bracknell, United Kingdom; 10Boehringer Ingelheim, Biberach, Germany; 11Boehringer Ingelheim, Reims, France; 12Boehringer Ingelheim, Ridgefield, CT, United States
Background: TPV is a novel non-peptidic protease inhibitor with activity against multiple-PIMethods: Patients with ≥3 protease mutations at codons 33, 82, 84, and 90 were randomized to: 1) TPV/r (500mg/200mg) control, 2) TPV/SQV/r (500mg/1000mg/200mg), 3) TPV/APV/r (500mg/600mg/200mg) or 4) TPV/LPV/r (500mg/400mg/100mg), all BID. All patients received a preselected investigator-defined optimized background regimen. For the first 2 weeks, all patients received an RTV-boosted single PI regimen. After 2 weeks of treatment, TPV was added to the dual-boosted PI arms. This planned interim analysis focused on primary safety and PK endpoints.
Results: Data was derived from 296 of 315 randomized patients who reached week 4 by the interim report cutoff date. Plasma Cmin in 173 patients were compared at weeks 1 and 2 (single-boosted PI) versus weeks 3 and 4 (dual-boosted PI); AUC and Cmax in 134 patients were compared at weeks 2 and 4. Co-administration of TPV/r and the other PIs was associated with decreases in PK parameters: SQV (AUC ↓70%, Cmax ↓66%, Cmin ↓81%), APV (AUC ↓45%, Cmax ↓40%, Cmin ↓56%), LPV (AUC ↓49%, Cmax ↓43%, Cmin ↓55%). All combinations were well tolerated during the 4-week time period, and the frequency of AEs was similar between all 4 arms at both weeks 2 and 4. The incidence of laboratory abnormalities was also similar in all 4 arms; triglyceride elevations were the most frequent abnormality.
Conclusions: This analysis demonstrates short-term safety of TPV/r alone or with APV, SQV, or LPV. Reductions in plasma PK parameters of SQV, APV, and LPV were observed when co-administered with TPV/r, though the clinical relevance of these reductions is not established.
The XV International AIDS Conference
Abstract no.
WeOrB1236
Suggested Citation
" S Walmsley , , et al.
Pharmacokinetics and safety of tipranavir/ritonavir (TPV/r) alone or in combination with saquinavir (SQV), amprenavir (APV), or lopinavir (LPV): Interim analysis of BI1182.51.
Oral Abstract session:
The XV International AIDS Conference:
Abstract no.
WeOrB1236"
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