Monday, Sep 14, 2009, 8:30 AM -11:00 AM
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
Monday, Sep 14, 2009, 10:00 AM -10:15 AM
HIV therapy; maturation inhibitors; PK
, N. BODSWORTH
, M. FIDLER
, C. WORKMAN
, A. BALCH
, H. BYAKAGWA
, A. BEELEN
Holdsworth House Med. Practice, Sydney, Australia,
Taylor Square Private Clinic, Sydney, Australia,
Myriad Pharmaceuticals, Salt Lake City, UT,
AIDS Res. Iniitative, Sydney, Australia,
St Vincents Hosp, Sydney, Australia.
Myriad Pharmaceuticals Inc
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
gene. PK/PD modeling suggests an
EC90 of 27 µg/mL.
Adults with HIV-1 and CD4≥100 cells/µL, plasma HIV RNA log
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.
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 log
copies/mL, CD4 T lymphocyte count 407 cells/µL. The mean day 15 change in log
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) C
of 200 mg bid dose was 46 (41-51) µg/mL and AUC
632 (571-699) hr*µg/mL; whilst 300mg bid had a C
of 72 (65-80) µg/mL and AUC
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%).
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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