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.

Abstract

OBJECTIVE:

The aim of this study was to investigate the safety and effectiveness 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 screened for diarrhea defined as at least three abnormal (i.e., soft or watery) stools and >200 g of abnormal stool weight over a 24-h period. Subjects discontinued all antidiarrheal agents >24 h before enrollment. Stool samples were studied for routine pathogens. Subjects received 500 mg p.o. of SP-303 or placebo every 6 h for 96 h (4 days). Stool frequency and weights were 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. There were no significant demographic differences between treatment arms. A total of 41 subjects (80%) were receiving antiretroviral therapy and 39 subjects (77%) were receiving at least one protease inhibitor. Stool studies revealed no pathogens in 48 of 51 patients (94%). There were no serious adverse events or laboratory abnormalities. The SP-303 treatment group demonstrated a mean reduction from baseline stool weight of 451 g/24 h versus 150 g/24 h with placebo on day 4 of treatment (p = 0.14), and a mean reduction in abnormal stool frequency of three abnormal stools in 24 h versus two in 24 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 compared 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 diarrhea.

• Authors: M Holodniy, J Koch, M Mistal, J M Schmidt, A Khandwala, J E Pennington, S B Porter
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 94 Issue 11 Pg. 3267-73 (Nov 1999) ISSN: 0002-9270 [Print] United States
• PMID: 10566728 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Antidiarrheals
• Antiviral Agents
• Biopolymers
• HIV Protease Inhibitors
• Placebos
• Catechin
• crofelemer

Topics

• Acquired Immunodeficiency Syndrome (complications)
• Administration, Oral
• Adult
• Anti-HIV Agents (therapeutic use)
• Antidiarrheals (administration & dosage, adverse effects, therapeutic use)
• Antiviral Agents (administration & dosage, adverse effects, therapeutic use)
• Biopolymers (adverse effects, therapeutic use)
• Catechin (adverse effects, analogs & derivatives, therapeutic use)
• Diarrhea (drug therapy, virology)
• Double-Blind Method
• Feces
• Female
• Follow-Up Studies
• HIV Protease Inhibitors (therapeutic use)
• Humans
• Male
• Middle Aged
• Placebos
• Safety