SOUTH SAN FRANCISCO, Calif., May 23 /PRNewswire-FirstCall/ -- Napo Pharmaceuticals, Inc., , which focuses on the development and commercialization of proprietary pharmaceuticals for the global marketplace in collaboration with local partners, announced that Trine Pharmaceuticals, Inc. (“Trine”) is presenting a poster detailing the results of a Phase 2a study conducted in 2006 for crofelemer for diarrhoea predominant irritable bowel syndrome (d-IBS) today at Digestive Disease Week in Washington, D.C. Trine licensed crofelemer for the d-IBS indication from Napo in June 2004. Trine has worldwide development and commercialization rights to crofelemer for d-IBS. The objective of the trial was to evaluate the safety and efficacy of crofelemer in men and women with d-IBS.
The trial was designed as a randomized double-blind placebo-controlled, dose-ranging (placebo, 125 mg, 250 mg, and 500 mg bid) study over a 12-week treatment period in 246 patients with d-IBS (Rome II criteria), including both males and females, whose average age was 50 years old.
IBS symptoms (pain, urgency, stool frequency and consistency, and adequate relief) were self-reported by the patients via an interactive voice response system (IVRS). Patients needed to exhibit active disease during the two-week baseline period as defined by a mean daily stool frequency greater than or equal to 2/day, pain score greater than or equal to 1 and stool consistency greater than or equal to 3 (5-point Lickert scale for pain and consistency) to be enrolled. Patients received treatment for 12 weeks followed by a two-week treatment free period.
Results: The 125 mg bid of crofelemer exhibited a consistent response during each month among most efficacy endpoints in women with d-IBS (see table) reaching statistical significance (p<0.05) for pain. Crofelemer had little effect on the stool consistency score, though there was a trend toward reduced stool frequency. Treatment benefits were not apparent in men, although relatively few men enrolled in the trial (13-16/group).
As with previous trials of crofelemer, no drug-related serious adverse events were reported. Adverse event rates were similar across all dose groups, although in the two highest doses (250 and 500 mg bid) there were a higher percentage of dropouts. There were no drug-related or dose-related differences in constipation. During the two-week treatment free follow-up period symptoms approached baseline levels.
Conclusion: Crofelemer, 125 mg bid, was safe and led to significant improvement in pain, and trends toward improvement in adequate relief, stool frequency and urgency. Endpoint Results(1) p-value (difference from Placebo) Pain score -0.42* 0.02 Frequency -0.7 0.13 (stools/day) Consistency Score -0.03 0.70 Urgency Free days +11.2% 0.20 Adequate Relief +16% 0.43 (1) Month 3 results (end of the three month treatment period); observed case analysis with disease outliers (mean baseline frequency >9 stools/day) removed from all groups. *statistically significant at p<0.05
Lisa A. Conte, Napo’s CEO commented: “The results of this trial using 125 mg bid of crofelemer, in addition to supportive pre-clinical data, was the impetus for our decision to incorporate this dosage in our adaptive design for the CRO-HIV trial. As we’ve said before, we were very encouraged by the study results, especially for pain, and look forward to the data from the ongoing Phase 2b trial. And, as has been seen in all previous studies of crofelemer, there were no adverse safety events reported.”
For more information please contact: Napo Pharmaceuticals, Inc Lisa Conte, Chief Executive Officer (001) + 650 616 1902 Charles Thompson, Chief Financial Officer (001) + 650 616 1903 Buchanan Communications 020 7466 5000 Tim Anderson, Mary-Jane Johnson Russo Partners, LLC (001) + 619 814 3510 Greg Geissman
D-IBS
Irritable Bowel Syndrome (“IBS”) is characterized by a constellation of gastro intestinal symptoms including diarrhea, constipation (or alternation of the two), urgency, and abdominal pain. IBS may affect up to 20 percent of the population in the US (estimates range from 15-20 percent; of whom 70 percent are women). More than 60 percent of the affected patients are managing either diarrhea predominant IBS (“D-IBS”) or alternating IBS.
IBS ranks second only to the common cold as a cause of lost work time in the U.S. In addition, the disease accounts for approximately 3 million physician visits in the U.S. each year, costing the U.S. economy an estimated $30 billion annually. The global market could be over $15 billion for a safe and effective D-IBS product.
About Trine
Trine has licensed the worldwide development and commercialization rights to crofelemer for the indication of diarrhea predominant Irritable Bowel Syndrome (IBS), in exchange for a profit split with Napo on sales of the product for that indication. Additionally, Trine has the commercialization rights to CRO-HIV in North America in exchange for a 50 percent profit split.
Trine is a venture capital-backed firm based in Newton, Mass. Trine is currently conducting a Phase 2b study of crofelemer for diarrhoea-predominant- IBS.
About Napo
Napo Pharmaceuticals Inc. focuses on the development and commercialization of proprietary pharmaceuticals for the global marketplace in collaboration with local partners. Napo was founded in November 2001 and is based in South San Francisco, Calif., with a subsidiary in Mumbai, India.
Napo’s late-stage proprietary gastro-intestinal compound, crofelemer, is in various stages of clinical development for four distinct product indications, including a late-stage Phase 3 program:
-- CRO-HIV for AIDS diarrhoea, Phase 3 -- CRO-IBS for diarrhea irritable bowel syndrome (“D-IBS”), Phase 2 -- CRO-ID for acute infectious diarrhea (including cholera), Phase 2 -- CRO-PED for pediatric diarrhea, Phase 1
The FDA has granted fast-track status to CRO-IBS and CRO-HIV.
Crofelemer, a proprietary patented agent, is extracted from Croton lechleri, a medicinal plant that can be sustainably harvested from several countries in South America. Experimental studies have shown that crofelemer inhibits chloride secretion across the CFTR transporter in various animal models of diarrhea, including cholera toxin treatment. Napo also plans to develop a clinical stage product, NP-500, for the treatment of insulin resistant diseases of Type II diabetes and metabolic syndrome (Syndrome X; pre-diabetic syndrome). Napo also has a plant library of approximately 2,300 medicinal plants from tropical regions and Napo has entered into screening relationships associated with this collection. Currently, products are based on the chemical and biological diversity derived from plants with medicinal properties, but future products may be in-licensed from other sources.
Napo has partnerships with Trine Pharmaceuticals, Inc. of the United States of America; Glenmark Pharmaceuticals Limited of India; and AsiaPharm Group Ltd. of China. For more information please visit www.napopharma.com
About Crofelemer
Crofelemer, a proprietary patented agent, is extracted from Croton lechleri, a medicinal plant which can be sustainably harvested from several countries in South America. Crofelemer is in various stages of clinical development for four distinct product indications, one in Phase 3, two in Phase 2, and one in Phase 1.
These products have been tested in trials involving approximately 1,500 patients in double-blind placebo-controlled, mostly published trials of AIDS diarrhea, diarrhea-predominant IBS, and acute infectious diarrhea. The products are generally well tolerated and have shown significant anti- diarrheal activities and improvement in gastrointestinal symptoms. Crofelemer produces several effects when administered orally providing for activity in several disease indications. Crofelemer’s anti-secretory mechanism reduces excess fluid secreted into the gastro-intestinal tract, while its anti- inflammatory and analgesic activity may provide the rationale for its significant benefit in abdominal pain. Crofelemer acts locally in the intestines, with limited systemic exposure.
Napo Pharmaceuticals, Inc.
CONTACT: Lisa Conte, Chief Executive Officer, (001)+650-616-1902, orCharles Thompson, Chief Financial Officer, (001)+650-616-1903, both of NapoPharmaceuticals, Inc.; Tim Anderson or Mary-Jane Johnson of BuchananCommunications, +020-7466-5000, or Greg Geissman of Russo Partners, LLC,(001)+619-814-3510, all for Napo Pharmaceuticals, Inc.
Web site: http://www.napopharma.com/
