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 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 261-273 |
| Number of pages | 13 |
| Journal | HIV Clinical Trials |
| Volume | 14 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 2013 |
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Keywords
- HIV
- antidiarrheals
- antiretroviral agents
- chloride channels
- diarrhea
- drug toxicity
- proanthocyanidins
ASJC Scopus subject areas
- Infectious Diseases
- Pharmacology (medical)
Cite this
Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT Trial) : A randomized, double-blind, placebo-controlled, two-stage study. / MacArthur, Rodger David; Hawkins, Trevor; Brown, Stephen; Lamarca, Anthony; Clay, Patrick; Barrett, Andrew; Bortey, Enoch; Paterson, Craig; Golden, Pamela; Forbes, William.
In: HIV Clinical Trials, Vol. 14, No. 6, 01.01.2013, p. 261-273.Research output: Contribution to journal › Article
}
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 David
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
UR - http://www.scopus.com/inward/record.url?scp=84890485224&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890485224&partnerID=8YFLogxK
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 Clinical Trials
JF - HIV Clinical Trials
SN - 1528-4336
IS - 6
ER -