Fulyzaq improves noninfectious diarrhea in patients with HIV on ART therapy

Noninfectious diarrhea in patients with HIV on antiretroviral therapy showed improvement after treatment with 125-mg delayed-release crofelemer (Fulyzaq, Salix Pharmaceuticals) tablets, according to a study in HIV Clinical Trials. 

The Antidiarrhea Therapy in HIV Disease-Emerging Treatment Concepts (ADVENT) trial concluded that crofelemer provides significant improvement in the symptomatic relief of noninfectious diarrhea with a safety profile similar to placebo and with no negative impact on clinical immune parameters (HIV viral load and CD4+ cell count).

The study design was 2-stage. In Stage 1, the optimal dose of Fulyzaq (125 mg twice daily) was determined by randomly assigning participants to placebo versus 1 of 3 doses of Fulyzaq in a 1:1:1:1 manner.  In Stage 2, using a completely new group of volunteers, participants were randomly assigned 1:1 to 125 mg Fulyzaq twice daily versus placebo. Both stages evaluated participants weekly. The evaluation period was 4 weeks, followed (in Stage 2) by a 6 month open-label period during which all participants received 125 mg of Fulyzaq twice daily. Cinical response was 2 or fewer watery bowel movements per week in 2 of the 4 weekly evaluation periods. Clinical responders went from an average of 20 watery bowel movements per week to an average of 2 watery bowel movements per week. Even among non-responders, there was an average of a 1-category improvement in stool consistency (eg, from watery to “mushy,” or from “mushy” to soft).

“Diarrhea was significantly and clinically meaningfully reduced in participants randomized to take Fulyzaq compared to those participants randomized to placebo,” said lead investigator Rodger D. MacArthur, MD, professor of medicine at Wayne State University, Division of Infectious Diseases, Detroit.

In addition, secondary measures of efficacy, such as improvement in stool consistency, also were significantly better in the Fulyzaq group compared to the placebo group. These differences were seen at the 4-week evaluation point, after which all participants were allowed to take open-label Fulyzaq for an additional 6 months. Response rates continued to improve on a weekly basis through the fourth month on Fulyzaq.  In addition, Fulyzaq had a side-effect profile comparable to placebo.

Fulyzaq works by inhibiting the intraluminal secretion of chloride ions and water by adhering to the chloride ion-secreting channels deep in the crypts of the gut lumen.  It is estimated that at least 15% of HIV-infected persons on antiretroviral therapy, especially those on protease inhibitors, have mild-to-moderate diarrhea.

“Antiretroviral-associated diarrhea often is a ‘classic’ secretory diarrhea that can negatively affect quality of life and daily functioning in affected individuals,” said Dr MacArthur. “Notably, Fulyzaq use was not associated with post-diarrhea constipation, a phenomenon that often is seen with the use of antimotility agents such as Imodium or Lomotil.”