A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS

OBJECTIVE: The aim of this study was to investigate the safety and effectiv eness of orally administered SP-303 in patients with AIDS and diarrhea. METHODS: This is a multicenter, phase II, randomized, double blind, placebo -controlled study. HIV-positive subjects with a history of a CD4 count <200 or an AIDS-defining illness were admitted to an inpatient study unit and s creened for diarrhea defined as at least three abnormal (i.e., soft or wate ry) stools and >200 g of abnormal stool weight over a 24-h period. Subjects discontinued all antidiarrheal agents >24 h before enrollment. Stool sampl es were studied for routine pathogens. Subjects received 500 mg y.o. of SP- 303 or placebo every 6 h for 96 h (4 days). Stool frequency and weights wer e recorded. Subjects were monitored for symptoms and side effects and were seen 1 wk later in follow-up. RESULTS: A total of 26 subjects received SP-303, and 25 received placebo. T here were no significant demographic differences between treatment arms. A total of 41 subjects (80%) were receiving antiretroviral therapy and 39 sub jects (77%) were receiving at least one protease inhibitor. Stool studies r evealed no pathogens in 38 of 51 patients (94%). There were no serious adve rse events or laboratory abnormalities. The SP-303 treatment group demonstr ated a mean reduction from baseline stool weight of 451 g/24 h vel-sw 150 g /24 h with placebo on day 4 of treatment (p = 0.14), and a mean reduction i n abnormal stool frequency of three abnormal stools in 24 h versus two in 2 4 h in the placebo group (p = 0.30). Daily measures analysis over 4 days of treatment demonstrated that SP-303 subjects had a significant reduction in stool weight (p = 0.008) and abnormal stool frequency (p = 0.04) when comp ared to placebo-treated subjects. CONCLUSIONS: SP-303 is safe and well tolerated. These results suggest that SP-303 may be effective in reducing stool weight and frequency in patients with AIDS and (C) 1999 by Am. Cell. of Gastroenterology.