|
Fifth International CongressDrug Therapy in HIV Infection22-26 October, 2000
|
BMS-232632 - CLINICAL TRIAL AI424–007: SAFETY, EFFICACY OF A ONCE DAILY PROTEASE INHIBITOR AT 24 WEEKS
P.J. Piliero1, I.M. Sanne2, R. Wood3, T. Kellher4, A. Mongillo4, A. Cross4, S. Schnittman 4 and M. Giordano4
1Albany Medical College, Albany, New York, USA; 2Johannesburg Hospital, Johannesburg, South Africa; 3Somerset Hospital, Capetown, South Africa; 4Bristol-Myers Squibb, Wallingford, Connecticut, USA
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.6
AIDS 2000, Oct 22-26;14(Suppl. 4);S7
BMS-232632 (BMS), a protease inhibitor (PI), has potent anti-HIV activity in vitro (EC50 2–5 nmol/l) and a favorable resistance profile. Phase I trials have shown it to be safe and well tolerated, and results of pharmacokinetic studies have supported qd dosing.
This phase II multinational, randomized trial compared the safety and antiviral activity of three dosages of BMS (200, 400, 500 mg qd) with those of nelfinavir (NFV, 750 mg tid) both as monotherapy (for 2 weeks) and in combination with ddI and d4T in antiretroviral-naïve subjects with HIV RNA ≥ 2000 copies/ml. After 80 subjects completed 12-week safety and antiviral activity evaluations in stage I, subjects were randomized into stage II (n = 300; 48-week safety and antiviral activity).
Results of stage I: treated for 24 weeks to date, 92 subjects (98 randomized); baseline median HIV RNA, 4.8 log10 copies/ml; median CD4+, 386 cells/ mm3. BMS has been safe and well tolerated alone and in combination. All treatment groups had reduced HIV RNA (~1.5 log10 copies/ml) after 2 weeks of monotherapy.
For BMS 200, 400 and 500 mg and NFV, respectively: HIV RNA < 400 copies/ml (%), 52, 52, 65, 67; HIV RNA < 50 copies/ml (%), 33, 20, 35, 38. Frequently reported adverse events were diarrhea (29%, BMS; 75%, NFV), mild infection and nausea (24%, BMS; 15%, NFV). Elevation of unconjugated bilirubin was the most common laboratory abnormality seen with BMS (62%). It was dose dependent, predominantly of grades 1–2, and not associated with elevations of liver enzymes. Changes in HIV RNA and CD4+ over time will be presented.
In conclusion, results at the 24-week (stage I) evaluation in trial AI424– 007 support this potent PI as a component of combination therapy due to its efficacy, safety and tolerability, and once daily dosing.
Presenting author: P.J. Piliero
Download Conferences Abstracts
2000-10-22
PL6-6
Originally published in AIDS Volume 14, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701
Copyright © 2000 - Lippincott Williams & Wilkins. All rights reserved. All abstracts from the Fifth International Congress Drug Therapy in HIV Infection, appearing on the AEGiS web site, are protected by United States copyright law and may not be reproduced, distributed, transmitted, displayed, or otherwise published without the prior written permission of Lippincott Williams & Wilkins. You may not alter or remove any trademark, copyright or other notice. However, provided that you maintain all copyright and other notices contained therein, you may download material (one machine readable copy and one print copy per page) for your personal, non-commercial use only.
http://www.aidsonline.com http://www.ovid.com
This information is designed to support, not replace, the relationship that exists between you and your doctor. ©1980, 2005. AEGiS.