Clinical Trial: Safety and Efficacy of AST-120 in the Treatment of Antibiotic-Refractory Pouchitis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Pilot Study of the Safety and Efficacy of AST-120 in the Treatment of Antibiotic-Refractory Pouchitis

Brief Summary: This is an open-label pilot study in which all patients will receive AST-120 for 4 weeks. Patients will discontinue antibiotics at study entry. They may continue other previously prescribed treatments (e.g., probiotics and/or nutritional agents) at the discretion of the study doctor. The purpose of the study is to assess whether the investigational medication AST-120 will be a safe and effective treatment for the symptoms of pouchitis, a chronic inflammatory condition, in patients whose symptoms have not responded well to antibiotics. An initial group of 10 patients will be enrolled. If there are no serious side effects associated with the study drug and at least 3 of the 10 patients respond, a second group of 10 patients may be enrolled. Patients will have clinic visits at the start of the study and at week 4. Patients will be checked by phone on a weekly basis for symptom response, compliance and development of side effects. Endoscopies will be performed at the start of the study and at week 4 or early termination.

Detailed Summary:

Patients with acute pouchitis are typically treated with metronidazole or ciprofloxacin for 10-14 days. Most patients with pouchitis respond to these or other antibiotics. Patients who experience frequent relapses and those with chronic pouchitis will require long term maintenance antibiotics. Probiotics may be considered as an alternate to chronic antibiotic therapy for maintenance of remission in chronic antibiotic-dependent pouchitis. In practice, we would institute maintenance therapy for patients who relapse at least 3 times within one year, or within 1 month of discontinuation of antibiotics. Among patients receiving maintenance antibiotics who develop loss of clinical benefit after prolonged treatment, rotation of three or four antibiotics in 1-week intervals may be beneficial. Patients who do not improve with single antibiotics may respond to combination therapy with two antibiotics. If not, they can be treated with topical or oral budesonide. Other options include topical mesalamine (enemas or suppositories), oral sulfasalazine or mesalamine, other topical or oral steroids, and possibly oral bismuth, azathioprine, 6-mercaptopurine or infliximab. However, there is little evidence base for these therapies in the literature, and many of these therapies are expensive and/or potentially toxic. A therapy that does not suppress the immune system, and that has little or no toxicity would be attractive for patients with antibiotic-refractory pouchitis.

AST-120 is manufactured by Kureha Corporation, Japan. The agent was approved in Japan in 1991 for the treatment of patients with chronic kidney disease(CKD). It is comprised of highly adsorptive, porous, spherical carbon particles and is packaged in 2 g sachets for oral administration designed for the treatment of gastrointestinal diseases. AST-120 consists of black microspheres approximately 0.2-0.4 mm in diameter with hig
Sponsor: Ocera Therapeutics

Current Primary Outcome:

  • Response as defined by a decrease in the Pouchitis Diseases Activity Index (PDAI) score of at least 3 points [ Time Frame: 4 weeks ]
  • Safety: Any adverse events (AEs) deemed possibly, probably, or definitely related to treatment with investigational product during 4 weeks of treatment [ Time Frame: 4 weeks ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Remission, as defined as a PDAI score of less than 7 points [ Time Frame: 4 weeks ]
  • Reduction of PDAI clinical symptom subscore of at least 1 point [ Time Frame: 4 weeks ]
  • Reduction of PDAI endoscopic subscore of at least 1 point [ Time Frame: 4 weeks ]
  • Reduction of PDAI histology subscore of at least 1 point [ Time Frame: 4 weeks ]
  • Need for rescue medication/quantity of antidiarrheal medication used during the last week of the trail compared to usage in the week prior to study entry [ Time Frame: 4 weeks ]
  • Quality of Life as measured by the Cleveland Global QoL instrument and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) [ Time Frame: 4 weeks ]
  • Significant change in clinical laboratory tests [ Time Frame: 4 weeks ]
  • Worsening GI symptoms (diarrhea, abdominal pain, urgency or bleeding) or new GI and extra-GI symptoms (e.g., headache, nausea, vomiting, constipation) [ Time Frame: 4 weeks ]
  • Significant change in physical examination, including vital signs (blood pressure, heart rate, respiration rate and temperature) [ Time Frame: 4 weeks ]


Original Secondary Outcome: Same as current

Information By: Ocera Therapeutics

Dates:
Date Received: December 20, 2007
Date Started: March 2007
Date Completion:
Last Updated: June 2, 2014
Last Verified: June 2014