A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection

A protein in the blood called tumor necrosis factor (TNF-alpha) is abnormally elevated in patients with HIV infection and may cause the body to produce more virus. In vitro studies have demonstrated that thalidomide reduces TNF-alpha levels and inhibits production of HIV. However, more information on the pharmacological and immunological aspects of thalidomide is needed.

Patients are randomized to receive oral thalidomide or matching placebo (3:1) at one of three dose levels daily for 8 weeks. All 12 patients at a dose level must receive treatment for at least 2 weeks before dose escalation in subsequent patients occurs. The MTD is defined as the dose level immediately below that at which 3 or more of 9 patients receiving thalidomide experience dose-limiting toxicity. Patients are followed for a total of 16 weeks.

PER 6/20/95 AMENDMENT: Patients in cohort 1 should discontinue the previous 50 mg formulation of thalidomide once the new formulation is available. Those patients may either wash out for 4 weeks and recommence the study or discontinue the study.