Product Information
Pumosetrag (DDP-733)
Pumosetrag, a 5-HT3 partial agonist that works locally within the upper GI tract, is being developed to treat GERD symptoms in patients who continue to experience heartburn and regurgitation while on PPIs or H2-antagonists. Pumosetrag works by activating the 5HT3 receptors found in the enteric nervous system of the GI tract, leading to an increase in motility. Preclinical findings include: increased lower esophageal sphincter pressure in cats, accelerated transit in rodent models of constipation, and increased interdigestive motor complexes in dog – all preclinical standard measures indicating a prokinetic effect. In volunteer clinical studies, pumosetrag demonstrated clinical activity in high fat provocative meal studies as measured by a reduction in the number of reflux episodes and shorter time that esophageal pH was below pH 4. The development plan for pumosetrag involves the following:
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DDP225
DDP225 is an investigational agent possessing both serotonin (5HT3) antagonist and noradrenaline reuptake inhibitor (NARI) activities. These pharmacological mechanisms are implicated in functional gastrointestinal disorders. DDP225 is being developed of as a treatment for patients with functional gastrointestinal disorders, specifically irritable bowel syndrome with diarrhea (IBS-d). Irritable bowel syndrome (IBS) is characterized by symptoms of abdominal pain, discomfort, and altered bowel function. Although not life threatening, it significantly reduces the quality of life with a major impact on the well being of the patient and also the social costs to the community. IBS affects approximately 12% of adults, with alterations in bowel function presenting as diarrhea or constipation or alternating between the two. IBS-d approximately affects half of all IBS patients. The commercial potential for a program like DDP225 in IBS-d has been estimated at over $1 billion in global peak sales. DDP225 was originally developed by Mitsubishi Pharma Corporation (now Mitsubishi Tanabe). The nonclinical safety of DDP225 has been extensively evaluated in studies of clinical pharmacology, toxicology and pharmacokinetics in multiple species including rat, dog, and monkey. DDP225 demonstrated no significant effects in assessments of antigenicity, mutagenicity, carcinogenicity or chromosomal aberration. Ten clinical studies were performed in Japan: six Phase 1 trials of safety and pharmacokinetics in healthy male volunteers with doses of 5 to 100 mg/day for durations of 1 to 14 days; and four Phase 2 trials in patients with depressive and neurodegenerative disorders with doses of 5 to 30 mg/day for durations of 6 to 12 weeks. Additionally, a Phase 1 clinical study was completed in healthy volunteers to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of lower doses of DDP225 (i.e., 1 mg, 3 mg, and 5 mg) administered for 56 days. To date, over 400 study subjects have been exposed to DDP225. No significant safety concerns limiting administration of DDP225 at the proposed doses (1-5 mg QD) were identified. Most recently, a Phase 2a study in female patients with IBS-d was conducted to characterize the safety and effectiveness of multiple doses and dose levels of DDP225.
DDP225 is available for licensing.