Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study.
HIV Clin Trials
; 14(6): 261-73, 2013.
Article
en En
| MEDLINE
| ID: mdl-24334179
ABSTRACT
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 ≤2 watery stools/week during ≥2 of 4 weeks). During the placebo-free extension phase, response (≤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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fármacos Gastrointestinales
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Infecciones por VIH
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Canales de Cloruro
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Proantocianidinas
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Diarrea
Tipo de estudio:
Clinical_trials
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Etiology_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2013
Tipo del documento:
Article