Presentation Abstract

Session: 143-HIV
Monday, Sep 14, 2009, 8:30 AM -11:00 AM
Presentation Title: H-1230 - Efficacy, Safety and Pharmacokinetics of MPC-4326 (Bevirimat Dimeglumine) 200mg bid and 300mg bid Monotherapy Administered for 14 days in Subjects with HIV-1 Infection
Location: Room 301
Presentation Number: H-1230
Pres. Time: Monday, Sep 14, 2009, 10:00 AM -10:15 AM
Category: H
Keywords: HIV therapy; maturation inhibitors; PK
Author(s): M. BLOCH1, N. BODSWORTH 2, M. FIDLER 3, C. WORKMAN 4, A. BALCH 3, H. BYAKAGWA 5, A. BEELEN 3;
1Holdsworth House Med. Practice, Sydney, Australia, 2Taylor Square Private Clinic, Sydney, Australia, 3Myriad Pharmaceuticals, Salt Lake City, UT, 4AIDS Res. Iniitative, Sydney, Australia, 5St Vincents Hosp, Sydney, Australia.
Financial Disclosures:  M. Bloch,
Myriad Pharmaceuticals Inc Role(s): Investigator, Received: Research Support.
Abstract: Background MPC-4326 (bevirimat dimeglumine) targets HIV maturation. Liquid formulation MPC-4326 is effective against HIV-1. Non-response has been associated with polymorphisms at 362 and 369-371 on the HIV-1 gag gene. PK/PD modeling suggests an in vivo EC90 of 27 µg/mL. Methods Adults with HIV-1 and CD4≥100 cells/µL, plasma HIV RNA log10 3.3-5.7copies/mL were randomized in an open-label, multi-centered study of MPC-4326 tablet formulation monotherapy 200mg bid vs 300mg bid for 14 days. Stratification was by previous therapy or naive. Full PK sampling was taken at days 1 and 14. Results Study enrolled 32 males, 26 were treatment-naïve. Median age was 40 years, 97% White, 94% had clade B virus, with mean plasma baseline HIV RNA 4.5 log10 copies/mL, CD4 T lymphocyte count 407 cells/µL. The mean day 15 change in log10 HIV RNA copies/mL (VLR) from baseline was -0.63, -0.48, -0.86 for total, polymorphic (362, 369-371) and wild type (WT) virus, respectively. Mean (90% CI) day 15 VLR from baseline for WT was -0.44 (-0.74, -0.12) and -1.22 (-1.51, -0.94) for 200mg bid and 300mg bid respectively, with difference between the doses -0.79 (p=0.003, 90% CI -1.21, -0.37). Geometric mean (90% CI) Cmin of 200 mg bid dose was 46 (41-51) µg/mL and AUC(0-tau) 632 (571-699) hr*µg/mL; whilst 300mg bid had a Cmin of 72 (65-80) µg/mL and AUC(0-tau) 973 (890-1064) hr*µg/mL. There were no study discontinuations, SAEs or grade III or IV events. Commonest AEs were headache (31%), diarrhea (19%) and nausea (16%). Conclusions MPC-4326 200mg bid and 300mg bid for 14 days in HIV-1 subjects was safe and well tolerated with trough concentrations above EC90. MPC-4326 300mg bid resulted in a significantly greater reduction in plasma HIV-1 RNA in subjects with WT virus.




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