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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: The aim of the study is to assess the safety and efficacy of an investigational agent, AST-120, in treating patients with active pouchitis. This is an open-label trial which means that all patients will receive AST-120 in 2g sachets (packets)three times a day for 4 weeks. All antibiotics, probiotics and nutritional agents must have been discontinued for at least 2 weeks prior to study entry. An initial group of 10 patients will be enrolled. If there are no serious adverse events associated with the study drug and at least 3 of the 10 patients respond, a second group of 10 patients will be enrolled. In the second group of patients, those patients who are considered responders or who are in remission are eligible to receive open-label AST-120 for as long as response is maintained up to a maximum of 52 weeks. Patients will have clinic visits at the start of the study and at week 4. If continuing on open label AST-120 after week 4, patients will have clinic visits every 12 weeks to assess the continuing safety and efficacy of AST-120. Endoscopies will be performed at the start of the study, week 4, week 28, week 52 or early termination.

Detailed Summary:

The management and prognosis vary in different types of pouchitis. For antibiotic-responsive pouchitis, the first-line therapy includes a 2-week course of metronidazole or ciprofloxacin. A relapsing course of pouchitis is common. Of the patients with acute pouchitis, 61% would develop at least one recurrence. Typically, patient's symptoms and endoscopic and histologic inflammation respond favorably to antibiotic therapy, but symptoms quickly recur when antibiotics are discontinued. This group of patients is classified as having antibiotic-dependent pouchitis and often requires long-term antibiotic or probiotic therapy to keep the disease in remission.

Although the majority of patients with active pouchitis respond favorably to antibiotic therapy, relapse is common, which often requires frequent antibiotic therapy. The concerns about frequent use of antibiotic agents are: 1)antibiotics such as metronidazole often cause adverse effects; 2)long-term or frequent use of antibiotics, including ciprofloxacin, metronidazole, and rifaximin, often leads to bacterial resistance. In clinical practice, we have encountered more and more patients with antibiotic-refractory pouchitis, which could largely be due to overuse of antibiotic agents; 3)UC patients with IPAA have an increased risk for the development of intra-abdominal infections, such as pouch leaks, abscess, and cholangitis from primary sclerosing cholangitis, which require antibiotic therapy with agents similar to the agents used in pouchitis. Bacterial resistance developed from the overuse of antibiotics for pouchitis might jeopardize the treatment of other intra-abdominal infections; 4) overuse of antibiotics can lead to overload of certain commensal bacteria or pathogenic bacteria, leading to pouch inflammation. Therefore, safe and effective agents are needed to treat active pouchitis, particularly on a long-term basis. Sponsor: Ocera Therapeutics

Current Primary Outcome:

  • Remission induction as defined by a Pouchitis Disease Activity Index (PDAI) score < 7 (Sandborn et al, Mayo Clin Proc 1994), as well as maintenance of remission over 12 months [ Time Frame: 4 weeks induction, 12 months maintenance of remission ]
  • Safety: Any adverse events (AEs) deemed possibly, probably, or definitely related to treatment with investigational product [ Time Frame: 4 weeks induction, 12 months maintenance of remission ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Response defined as a > or = 3 point reduction in the 18-point PDAI scoring system [ Time Frame: 4 weeks, weeks 28 and 52 ]
  • Reduction of PDAI clinical symptom score, range from 0 to 6 (e.g., stoll frequency returns to the normal baseline) [ Time Frame: 4 weeks, weeks 28 and 52 ]
  • Reduction of PDAI endoscopic score, range from 0 to 6 [ Time Frame: 4 weeks, weeks 28 and 52 ]
  • Reduction of PDAI histology score, range from 0 to 6 [ Time Frame: 4 weeks, weeks 28 and 52 ]
  • Need for rescue medication or increased quantity of antidiarrheal medication used during the trial [ Time Frame: 4 weeks, weeks 28 and 52 ]
  • Quality of Life (Cleveland Global Quality of Life [CGQL] and Short Inflammatory Bowel Disease Questionnaire [SIBDQ] [ Time Frame: 4 weeks, through 52 weeks ]
  • Clinical laboratory tests including liver transaminases and alkaline phosphatase [ Time Frame: 4 weeks, through 52 weeks ]
  • Worsening GI symptoms (diarrhea, abdominal pain, urgency or bleeding) or new GI and ex-intestinal systemic symptoms (such as headache, nausea, vomiting, and constipation) [ Time Frame: 4 weeks, through 52 weeks ]
  • Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature) [ Time Frame: 4 weeks, through 52 weeks ]


Original Secondary Outcome: Same as current

Information By: Ocera Therapeutics

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