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 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.
Holodniy
M
M
AIDS Research Center, VA Palo Alto Health Care System and Stanford University, California 94304, USA.
Koch
J
J
Mistal
M
M
Schmidt
J M
JM
Khandwala
A
A
Pennington
J E
JE
Porter
S B
SB
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000930:Antidiarrheals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001704:Biopolymers / Q000009:adverse effects / Q000627:therapeutic use*; D002392:Catechin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003967:Diarrhea / Q000188:drug therapy* / Q000821:virology; D004311:Double-Blind Method; D005243:Feces; D005260:Female; D005500:Follow-Up Studies; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012449:Safety; D044945:Proanthocyanidins
D019380:Anti-HIV Agents; D000930:Antidiarrheals; D000998:Antiviral Agents; D001704:Biopolymers; D002392:Catechin; D017320:HIV Protease Inhibitors; D010919:Placebos; C546704:crofelemer; D044945:Proanthocyanidins