A double-blind placebo-controlled study was conducted in 100 patients with confirmed severe cholera. Patients were randomized to placebo or 125mg crofelemer every six hours or 250mg crofelemer every six hours in a 1:2:2 randomization scheme.
The purpose of the trial was to obtain a therapeutic proof-of-concept in the treatment of cholera, by a reduction in the life-threatening fluid loss characteristic of cholera infection. In addition to receiving crofelemer, all patients received a single oral dose of azithromycin and rehydration therapy.
These severely ill cholera patients, even when receiving the antibiotic azithromycin and rehydration therapy, averaged approximately 8.5 liters of stool volume output during the first 24 hour period. The primary endpoint in this study was the reduction in stool volume output normalized to the body weight of the cholera patients.
Following the exclusion of three outlier patients, the data demonstrates that a crofelemer dose of 125mg every six hours reduced the amount of stool volume output normalized to body weight by 32% (p=0.028, Mann-Whitney test) in the first six hour period (0-6 hours). Approximately 31% reduction in normalized stool volume output was also observed during the first 12 hour period (0-12 hours) with crofelemer 125mg every six hours (p=0.072, Mann-Whitney test).
The higher dose of crofelemer (250mg every six hours) also showed a trend towards significance in the first 12 hour period (0-12 hours, p=0.155, Mann-Whitney test). Crofelemer was well tolerated in cholera patients. Crofelemer was safely and effectively used in combination with the antibiotic, azithromycin, and rehydration therapy.
Both Napo and International Centre for Diarrhoeal Disease Research, Bangladesh, upon receipt of additional funding, would like to continue with studies ranging to lower dosing regimens with crofelemer, and also include the treatment of children with development of a pediatric formulation of the product. Elements of the cholera study in Bangladesh were funded by the National Institutes of Allergy and Infectious Disease.