Arverapamil (AGI-003)
Altered intestinal motility is a major component of IBS and patients are diagnosed and sub-typed according to their predominant symptom of bowel disturbance. Arverapamil is being developed in an oral dosage form for the treatment of diarrhoea-predominant irritable bowel syndrome (“IBS-D”) in both men and women. The IBS-D segment of the IBS market is estimated to account for at least one-third of all IBS patients and there are currently an estimated 6 million diagnosed IBS-D patients in developed markets who could benefit from safe and effective drug therapy. IBS-D represents a significant unmet medical need as there are currently few or no safe and effective therapeutic options available to these patients.
In June 2006 we announced the positive outcome of a Phase II clinical trial evaluating arverapamil in 129 patients (male and female) meeting ROME II criteria (modified) for non-constipation predominant IBS. The clinical trial was a randomised, double-blind, placebo-controlled, parallel group, forced dose-escalation study (dose escalated every 4 weeks), which evaluated the efficacy of arverapamil versus placebo over a 12-week period.
Using an intent-to-treat analysis and the entire 12 weeks of therapy, the arverapamil treated patients showed a significantly higher response rate than placebo based on patient global impression (56.9% vs. 37.5%) and based on relief of abdominal pain/discomfort (56.9% vs. 43.8%). No differences between treatments were seen in use of rescue medications. Compared with placebo, the arverapamil treated patients also showed significant favourable differences in change from baseline in a) the Bristol Stool Scale at week 8 and week 12, b) bloating and stool frequency at week 4 and c) urgency and composite gastrointestinal symptoms at week 4 and week 12.
Patients also completed the IBS Quality-of-Life (QOL) survey, a validated 34-item condition-specific QOL survey consisting of 8 subscales at the 4, 8 and 12 week visits. Scores can range from 0 to 100 with a higher score indicating better QOL. Significant improvements were recorded in the arverapamil treated patients compared with placebo at week 12 for both the total score (24.9 points vs. 3.55 points) and for all eight sub-scales and at week 8 for total score and each of the sub-scales with the exception of sexual and relationship sub-scales. Arverapamil was generally well tolerated and there were no serious adverse events.
The results of this Phase II trial demonstrate the efficacy of arverapamil in IBS patients with non-constipation predominant symptoms and AGI expects that this drug will be of benefit to those IBS-D patients who are currently without a safe and effective therapy for this condition. AGI believes arverapamil may also have utility in the treatment of other diarrhoea- related conditions.
