 |
|
|
| |
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
ABSTRACT
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.
OBJECTIVE
Primary: Characterize the pharmacokinetics of MPC-4326 100 mg tablets administered for 15 days in HIV infected subjects
Secondary:
-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
STUDY DESIGN
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
|
| |
|
|
|
|
|
