icon-folder.gif   Conference Reports for NATAP  
  49th ICAAC
San Francisco, CA
September 12-15, 2009
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Pharmacokinetics and Safety of a Novel 100 mg Tablet Formulation of MPC-4326 in Subjects with HIV-1 Infection
  Reported by Jues Levin
ICAAC Sept 14 2009 San Francisco
J. Lalezari1, G. Richmond2, M. Thompson3, C. Cohen4, G. Mather5, A. Balch5, A. Beelen5 1Quest Clinical Research, San Francisco, CA; 2Private Practice, Ft. Lauderdale, FL; 3AIDS Research Consortium, Atlanta, GA; 4CRINE, Boston, MA; 5Myriad Pharmaceuticals, Inc., Salt Lake City, UT


Background: The HIV-1 maturation inhibitor MPC- 4326 (bevirimat dimeglumine) potently inhibits infectivity by preventing protease-mediated Gag cleavage at CA-SP1. PK/PD modeling predicted an in vivo EC90 of 27 µg/mL. This study was designed to characterize the steady-state pharmacokinetics of MPC-4326 100 mg novel tablet formulation.
Methods: Eligible subjects with undetectable virus were randomized to MPC-4326 200 mg BID, 300 mg QD or 400 mg QD for 15 days in addition to their HAART. PK sampling occurred on Days 1, 14, and 15. MPC-4326 was given after a high-fat breakfast on Day 15. Standard non-compartmental analysis was used to calculate pharmacokinetic parameters. Statistical evaluation of food effect was based on a comparison of the no effect boundary of 80-125% to a 90% confidence interval on ratio of geometric means Fed:Fasted for Cmax and AUC(0-tau) .
Results: A total of 35 subjects were enrolled and 33 completed the PK assessments.The 90% CI for all Cmax and AUC ratios fell within the no effect boundary. There was one SAE (hip fracture) unrelated to study medication. The most common AEs were diarrhea (31.4%), abdominal cramping, headache and nausea (8.6% each).
Conclusions: The MPC-4326 novel 100 mg tablet formulation was well tolerated and BID dosing maintained Cmin above the estimated EC90 . Food had minimal effect on MPC-4326 exposure at steady-state whilst delaying Tmax 3-4 hrs.
Primary: Characterize the pharmacokinetics of MPC-4326 100 mg tablets administered for 15 days in HIV infected subjects
-To evaluate the effect of food on the pharmacokinetics of MPC-4326 100 mg tablets
-To assess the safety and tolerability of a 100 mg tablet formulation of MPC-4326
Open-label, randomized, parallel group study
Oral doses of MPC-4326 taken as 100 mg tablets 200 mg BID, 300 mg QD or 400 mg QD
Study medication taken fasted days 1-14; fed high fat meal prior to dosing on day 15