Clinical studies

Atiprimod successfully completed single and multiple dose Phase I clinical trials in patients with rheumatoid arthritis (RA). In the initial Phase I study, 28 patients were given single escalating doses of drug (0.002 - 1.0 mg/kg), with a 4-month follow-up. Atiprimod was well tolerated, displaying no clinically relevant changes in any laboratory parameters. In particular, liver function tests remained in the normal range. The second Phase I study involved a 28-day multiple-dose-rising study in 35 RA patients. The study evaluated effect of food on bioavailability, as well as the safety and pharmocokinetics of repeat dosing. Dosages included 0.1, 1 .0, 5.0, and 10 mg/day plus a 14-day cohort at 30 mg/day, with 4-month follow-up. All doses were well tolerated and clinical tests were unremarkable. Individuals from the 2 Phase I safety studies were also involved in a long-term, open-label extension trial utilizing 5-mg daily doses of drug. Forty-three patients entered the study and remained on drug as long as 12 months. Clinical laboratory results for all patients were unremarkable; in particular liver enzyme levels remained with the normal range in all patients throughout the study period. Significantly, reductions in tender and swollen joint counts were noted in a number of subjects during the course of the first 28-day dosing period. A Phase II multiple-center trial plan to further evaluate Atiprimod in RA patients was accepted by the FDA. The trial was never implemented.