Napo Pharmaceuticals, Inc., is pleased to announce the positive results of a successfully completed phase 2 trial for CRO-ID (crofelemer for the treatment of acute adult infectious diarrhea) conducted by its partner, Glenmark Pharmaceuticals Limited.
The primary endpoints of the trial were stool weight, duration of diarrhea, stool frequency and stool consistency; additional endpoints followed include degree of patient dehydration and reduction in gastrointestinal index score. The conclusions from the study were that treatment with crofelemer was well tolerated and resulted in statistically significant improvements in all the primary endpoints and statistically significant reduction in the additional endpoints as well. Overall clinical success was achieved in 79.1 per cent of the valuable patients receiving crofelemer compared to 28.2 per cent of the valuable patients receiving placebo. There were no drug related adverse events associated with crofelemer.
The phase II study was a randomised, parallel group, double-blind, placebo-controlled which enrolled 98 Indian adult male and female patients aged between 18 to 65 years with acute diarrhea defined as the occurrence of three or more unformed stools (soft or watery consistency) within the 24-hour period preceding entry into the study. Patients suffering from acute infectious diarrhea were dosed 250 mg of crofelemer, QID (4 times per day) until recovery or for a maximum of three days. Details regarding the stool weight, stool frequency, stool consistency, duration of diarrhea, and other gastrointestinal symptoms were recorded by the investigators at baseline, and days 1, 2 and 3 of treatment. All patients had a scheduled follow-up visit 30 days after the end of the last dose.
In conclusion, adult Indian patients with infectious diarrhea treated with crofelemer showed a faster recovery with the first dose itself as observed by the reduction in stool weight, stool frequency and passage of formed stools. Crofelemer was well tolerated and most adverse events were mild to moderate in severity and not different from the placebo group. Furthermore, the adverse events disappeared with continued therapy and causality was not attributed to the treatment.
Glenmark is Napo's exclusive licensee for crofelemer in over 140 countries for the indications of CRO-HIV, CRO-ID and CRO-PED. Glenmark anticipates it will begin another dose-ranging trial for CRO-ID in 2008, investigating the opportunity to treat with lower doses and lower frequency of dosing.
In combination with previous success in treating infectious diarrhea in travelers in Mexico and Jamaica with crofelemer, Napo is investigating the regulatory pathway to file an NDA for acute infectious diarrhea treatment with crofelemer coincident with its on-going phase 3 programme in chronic diarrhea in people living with HIV/AIDS (CRO-HIV). Napo is targeting an NDA filing for CRO-HIV around the end of the year. Napo has exclusive worldwide rights to crofelemer in all western territories. Lisa A. Conte, CEO of Napo Pharmaceuticals, Inc, said, "Napo is extremely pleased to see the achievement of statistical significance in this trial and that once again, crofelemer's safety profile has been confirmed.
The success of this study is a very important step for Glenmark in its goal to develop crofelemer for CRO-ID in its territories. For Napo, it represents a significant step toward the realization of royalties from sales of crofelemer by Glenmark in over 140 countries, and may address the devastating morbidity and mortality issues associated with the billions of episodes of diarrhea in developing countries with a novel anti-secretory mechanism of action.
Pravin Chaturvedi, president and chief scientific officer of Napo said, "The effects of crofelemer in this study of secretory diarrhea caused by infectious pathogens provides additional support and confidence to the mechanistic rationale for treating diarrhea in patients with different causes. In conjunction with the on-going phase III trial that Napo is conducting in chronic diarrhea in people living with HIV/AIDS, this Glenmark trial will provide a new pathway to a therapy for both acute and chronic secretory diarrhea. Glenmark expects to file for approval of crofelemer for the CRO-ID indication in India in 2009, and, in combination with Napo's NDA programmes for crofelemer, the various approvals may allow for subsequent approvals in the multiple countries where Glenmark is a licensee."