Second International Congress Drug Therapy in HIV Infection 18-22 November 1994 Glasgow, UK

SAFETY, PHARMACOKINETICS AND VIROLOGICAL/IMMUNOLOGICAL EFFICACY OF ABT-538, A HIV -PROTEASE INHIBITOR. A RANDOMISED, PLACEBO-CONTROLLED PHASEVII STUDY.

S.A. Danner, D.A. Cooper, F. Gudiol, J. Gonzales, J. Tor, R. Rubio, J. Valdes, J.M.Leonard.
Academic Medical Centre, Amsterdam, St. Vincent Hospital, Sydney, Hospital Priceps d'Espanya, Barcelona, Hospital La Paz, Madrid, H. Germans Trias I Pujol, Barcelona, Hospital Doce De Octubre, Madrid, Abbott Labs. Abbott Park, Ill.

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 11.2
AIDS 1994, Vol. 8 (Suppl. 4);S9

ABT-538 is a highly specific inhibitor of HIV protease with potent in-vitro activity. Single and multiple dose studies in humans safely achieved blood drug levels in many fold excess above the in-vitro EC₉₀, of the compound. This trial, designed to assess the activity of ABT-538, consisted of two escalating dose groups studied in a randomized, placebo-controlled, double-blind fashion. Within dose group I 38 patients were randomized to placebo, 300 mgm or 400 mgm BID; in dose group II, 37 patients were randomized to placebo, 500 mgm or 600 mgm BID. Patients were HIV-p24 antigen positive at entry and had at least 50/mm³ CD4+ lymphocytes. After a two weeks washout period, patients were treated for 4 weeks, followed by an optional dose blinded extension in which all patients continued to receive active drug at the original dose or were randomized to one of the doses within the group if they had initially received placebo.

All patients in dose group I who received ABT-538 had HIV-p24 antigen declines in excess of 40% from baseline; b-DNA and p24 antigen responses were correlated (60% concordance). Many patients who received active drug in group I had CD4+ lymphocyte increases in excess of 100% over baseline during the active study period. The drug had been well tolerated during the study. Although dose group II is still blinded, these results indicate ABT-538 has potent in-vivo antiretroviral activity. Full results from both groups will be presented at the conference.

Presenting author: S.A. Danner

1994-11-18
11.2

Originally published in AIDS Volume 8, 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

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