TY - JOUR
T1 - Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT Trial)
T2 - A randomized, double-blind, placebo-controlled, two-stage study
AU - Macarthur, Rodger
AU - Hawkins, Trevor
AU - Brown, Stephen
AU - Lamarca, Anthony
AU - Clay, Patrick
AU - Barrett, Andrew
AU - Bortey, Enoch
AU - Paterson, Craig
AU - Golden, Pamela
AU - Forbes, William
PY - 2013/1/1
Y1 - 2013/1/1
N2 - Background: HIV-associated diarrhea remains a significant concern with limited treatment options. Objective: To determine the optimal dose, efficacy, and safety of crofelemer for noninfectious diarrhea. Methods: This randomized, double-blind, phase 3 trial used a 2-stage design. Both stages included 2-week screening, 4-week placebo-controlled treatment, and 20-week placebo-free (open-label) extension phases. In stage I, 196 HIV-seropositive patients with chronic diarrhea were randomized to crofelemer 125 mg, 250 mg, or 500 mg or placebo twice daily. Using a prospective analysis, the 125-mg twice-daily dose was selected for stage II. In stage II, 180 new patients were randomized to crofelemer 125 mg twice daily or placebo for 4 weeks. Primary efficacy analysis was the percentage of patients (stages I/II combined) who achieved clinical response (defined as â‰2 watery stools/week during ≥2 of 4 weeks). During the placebo-free extension phase, response (â‰2 watery stools) was assessed weekly. Results: Significantly more patients receiving crofelemer 125 mg achieved clinical response versus placebo (17.6% vs 8.0%; one-sided, P = .01). Crofelemer 125 mg resulted in a greater change from baseline in number of daily watery bowel movements (P = .04) and daily stool consistency score (P = .02) versus placebo. During the placebo-free extension phase, percentages of weekly responders ranged from 40% to 56% at weeks 11 to 24. Crofelemer was minimally absorbed, well tolerated, did not negatively impact clinical immune parameters, and had a safety profile comparable to placebo. Conclusions: In HIV-seropositive patients taking stable antiretroviral therapy, crofelemer provided significant improvement in diarrhea with a favorable safety profile.
AB - Background: HIV-associated diarrhea remains a significant concern with limited treatment options. Objective: To determine the optimal dose, efficacy, and safety of crofelemer for noninfectious diarrhea. Methods: This randomized, double-blind, phase 3 trial used a 2-stage design. Both stages included 2-week screening, 4-week placebo-controlled treatment, and 20-week placebo-free (open-label) extension phases. In stage I, 196 HIV-seropositive patients with chronic diarrhea were randomized to crofelemer 125 mg, 250 mg, or 500 mg or placebo twice daily. Using a prospective analysis, the 125-mg twice-daily dose was selected for stage II. In stage II, 180 new patients were randomized to crofelemer 125 mg twice daily or placebo for 4 weeks. Primary efficacy analysis was the percentage of patients (stages I/II combined) who achieved clinical response (defined as â‰2 watery stools/week during ≥2 of 4 weeks). During the placebo-free extension phase, response (â‰2 watery stools) was assessed weekly. Results: Significantly more patients receiving crofelemer 125 mg achieved clinical response versus placebo (17.6% vs 8.0%; one-sided, P = .01). Crofelemer 125 mg resulted in a greater change from baseline in number of daily watery bowel movements (P = .04) and daily stool consistency score (P = .02) versus placebo. During the placebo-free extension phase, percentages of weekly responders ranged from 40% to 56% at weeks 11 to 24. Crofelemer was minimally absorbed, well tolerated, did not negatively impact clinical immune parameters, and had a safety profile comparable to placebo. Conclusions: In HIV-seropositive patients taking stable antiretroviral therapy, crofelemer provided significant improvement in diarrhea with a favorable safety profile.
KW - HIV
KW - antidiarrheals
KW - antiretroviral agents
KW - chloride channels
KW - diarrhea
KW - drug toxicity
KW - proanthocyanidins
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U2 - 10.1310/hct1406-261
DO - 10.1310/hct1406-261
M3 - Article
C2 - 24334179
AN - SCOPUS:84890485224
VL - 14
SP - 261
EP - 273
JO - HIV Research and Clinical Practice
JF - HIV Research and Clinical Practice
SN - 2578-7489
IS - 6
ER -