Safety and Efficacy of AST-120 in Patients With Non-Constipating Irritable Bowel Syndrome

• Percent of patients who achieve at least a 50% reduction in the number of days with abdominal pain during the final 2 weeks of the double-blind treatment course. [ Time Frame: Eight weeks ] [ Designated as safety issue: No ]
  
• Safety endpoint is adverse events (AEs) deemed possibly, probably, or definitely related to treatment with investigational product during the double-blind treatment course. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  

• Percent change in the IBS QOL score. [ Time Frame: Eight weeks ] [ Designated as safety issue: No ]
  
• Percent change in HADS score. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  
• Percent change in Bristol Scale score. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  
• Percent change in individual items in the IBS Symptom Severity questionnaire. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  
• Durability of effect after the first eight weeks of treatment. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  
• Change in clinical laboratory tests from Baseline to Week 8 and to Week 18. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  
• Any adverse event occurring after Week 8. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  
• Physical examinations, vital signs (blood pressure, heart rate, respiration and temperature). [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  

Patients experiencing non-constipating IBS will be randomized to one of two arms in the study: the experimental drug AST-120 or placebo. Patients will take 2g of AST-120 or placebo three times per day for eight weeks. After the 8 week course, patients will receive an additional 8 weeks single blind treatment, after a one week washout period.

The experimental drug AST-120 is composed of black, odorless spherical carbon particles in 2g sachets (aluminum foil pouches). The placebo consists of microcrystalline cellulose spheres, Celphere CP-305 stained to match the appearance of AST-120, in 2g sachets (aluminum foil pouches). Both AST-120 and placebo are oral (taken by mouth) preparations. Both are tasteless. To take the product, patients will tear open the sachet, drop the contents directly on their tongue and wash it down with 8 ounces of water.

Patients will be expected to participate in up to 10 visits, approximately three by telephone and the remainder of visits are in-clinic. At these visits, patients will undergo a number of tests including: hematology panel, lactose intolerance testing, physical exams, pregnancy tests, evaluations based on the following scales: The Bristol Stool Scale, IBS Severity Scale, IBS Quality of Life, SCL-90R.

Provided the patient has been stable for eight weeks prior to their baseline visit, they will be allowed to take the following medications: drugs that inhibit gastric secretion (histamine blockers, proton pump inhibitors), benzodiazepines and Imidazopyridines (short acting, nonbenzodiazepine hypnotics) for sleep (dose must be consistent with the use of a sleep agent) aspirin at a cardiovascular prophylactic dose (75-150 mg/day) and paracetamol. Antidepressants for non-IBS symptoms are allowed. Loperamide will be permitted as a rescue for diarrhea only when patients are experiencing at least 3 liquid or soft stools in one day. However, Loperamide is prohibited during the two week screening period.

Patients will not be allowed to take the following medications whilst on trial and these therapies must have been discontinued by at least two weeks prior to their baseline visit: probiotics, neuroleptics, antidepressants for IBS symptoms, daytime tranquilizers, prokinetics, spasmolytics, analgesics, other investigational agents and any over-the-counter medications.

Patient will be required to keep a diary during the study