[3] SAFETY AND EFFICACY OF TIPRANAVIR, A NON-PEPTIDIC PROTEASE INHIBITOR, IN MULTIPLE PI-FAILURE PATIENTS (BI 1182.2)

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] SAFETY AND EFFICACY OF TIPRANAVIR, A NON-PEPTIDIC PROTEASE INHIBITOR, IN MULTIPLE PI-FAILURE PATIENTS (BI 1182.2)

[AUTHOR(S):] Curry R, Markowitz M, Slater L, Neubacher D, Robinson P, Cotton G, BI 1182.2 Study Team
Boehringer Ingelheim, Ridgefield, CT, USA

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 3

[ABSTRACT:] Object Of Study: Tipranavir (TPV) is the first in a new class of non-peptidic PIs (NPPIs) and shows potent activity in vitro against broadly PI-resistant HIV strains. This phase II, open-label study randomized NNRTI naïve patients, who had clinically failed two or more PI-containing regimens (HIV-1 RNA >= 5K c/ml on the current PI regimen), to 2 TPV and low dose ritonavir (RTV) regimens + efavirenz (EFV) and 1 new NRTI.

Methods: The study began with TPV 300mg hard-filled capsules (hfc), then switched to TPV 250mg soft-gel capsules (Self Emulsifying Drug Delivery System, SEDDS). Pts (n=41) were randomized to: Grp A (n=19): TPV (hfc 1200mg-->SEDDS 500mg BID) + RTV 100mg BID + EFV 600mg QD + 1 NRTI; or Grp B (n=22): TPV (hfc 2400mg-->SEDDS 1000mg BID) + RTV 200-->100mg BID + EFV 600 mg QD + 1 NRTI.

Results: ITT analysis results at 24 wks are presented. Median decrease in HIV RNA from baseline (BL) was 2.69 log₁₀ (BL = 4.48 log₁₀) in Grp A and 2.59 log₁₀ (BL = 4.43 log₁₀) in Grp B (p= 0.24). The proportion of pts with HIV RNA <400 c/ml was: 77.8% (14/18; 1 pt with no observations after BL excluded) Grp A and 50% (11/22) Grp B, p=0.10. The proportion <50 c/ml was 61.1% (11/18) Grp A and 50% (11/22) Grp B, p=0.54. The median CD4⁺ cell count increased by 130 (BL=275) and 111 (BL=211) cells in Grps A and B, respectively, p=0.69. By 24 wks, 9 pts (A=2, B=7) had withdrawn: 3 for viral rebound (A=1, B=2), 3 lost to follow-up (B=3), 2 due to adverse events (AE) (A=1, B=1) and 1 for a protocol violation (B=1). Three pts reported serious AEs; 1 report, non-cardiac chest pain, was possibly study-drug related. The most common drug-related AEs were diarrhea, 46%; nausea, 27%; GGT incr., 20%; vomiting, 17%; dizziness, 17%; abnormal dreams, 15%; and SGPT incr., 15%.

Conclusions: Both dose regimens of TPV and low dose RTV plus EFV and 1 new NRTI were well tolerated and demonstrated durable, potent antiviral activity in a population of patients with multiple PI failure.

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