Safety and Efficacy of AST-120 in the Treatment of Pouchitis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ocera Therapeutics
ClinicalTrials.gov Identifier:
NCT00583076
First received: December 20, 2007
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Pouchitis
Drug: AST-120
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of the Safety and Efficacy of AST-120 in the Treatment of Active Pouchitis

Resource links provided by NLM:


Further study details as provided by Ocera Therapeutics:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response defined as a > or = 3 point reduction in the 18-point PDAI scoring system [ Time Frame: 4 weeks, weeks 28 and 52 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Reduction of PDAI endoscopic score, range from 0 to 6 [ Time Frame: 4 weeks, weeks 28 and 52 ] [ Designated as safety issue: No ]
  • Reduction of PDAI histology score, range from 0 to 6 [ Time Frame: 4 weeks, weeks 28 and 52 ] [ Designated as safety issue: No ]
  • Need for rescue medication or increased quantity of antidiarrheal medication used during the trial [ Time Frame: 4 weeks, weeks 28 and 52 ] [ Designated as safety issue: Yes ]
  • Quality of Life (Cleveland Global Quality of Life [CGQL] and Short Inflammatory Bowel Disease Questionnaire [SIBDQ] [ Time Frame: 4 weeks, through 52 weeks ] [ Designated as safety issue: No ]
  • Clinical laboratory tests including liver transaminases and alkaline phosphatase [ Time Frame: 4 weeks, through 52 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature) [ Time Frame: 4 weeks, through 52 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: February 2007
Study Completion Date: May 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
AST-120, 2grams, three times daily
Drug: AST-120
AST-120, 2grams,three times daily for 4 weeks. Responders in the second cohort of patients are eligible to receive AST-120 for up to 52 weeks.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a current episode of active pouchitis (defined as having a PDAI score > 7) after IPAA for UC confirmed by endoscopy and histology
  • Patients with active pouchitis who have never been treated with antibiotics (antibiotic-naive) or who have been previously treated with antibiotics and responded. Antibiotic-dependent patients may be enrolled as long as antibiotic use is discontinued for at least two weeks prior to study entry. Antibiotic-dependent pouchitis is defined as a condition in which a patient with frequent episodes (> or = 4 episodes per year) of pouchitis or persistent symptoms requires long-term, continuous antibiotic or probiotic therapy to keep the disease in remission.
  • Able to give informed consent
  • Able and willing to comply with all study procedures
  • Females must be post-menopausal, surgically incapable of bearing children, or practicing a reliable single barrier method of birth control (condom, intrauterine devices, spermicide and barrier, Depot). Partner/spouse sterility may also qualify at the investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline. Oral contraceptives are not acceptable as there is a potential interaction with AST-120.

Exclusion Criteria:

  • Patients previously treated with infliximab or any investigational immunosuppressant/immunomodulator
  • Patients whose condition is severe enough that, in the investigator's opinion, withholding antibiotics for 4 weeks during the AST-120 trial is not feasible
  • Patients undergoing chemotherapy for the treatment of cancer
  • Antibiotic use within 2 weeks prior to the entry of the study
  • Crohn's disease of the pouch, including inflammatory, fibrostenotic, or fistulizing phenotypes, based on the previously established diagnostic criteria (Shen B, et al. Am J Gastroenterol 2006 in press)
  • Active specific infection of the pouch: cytomegalovirus infection and C. difficile infection
  • Patients with chronic antibiotic-refractory pouchitis. Antibiotic- refractory pouchitis is defined as a condition where a patient fails to respond to a 4 week course of a single antibiotic (metronidazole or ciprofloxacin), requiring prolonged therapy of > or = 4 weeks consisting of 2 antibiotics, oral or topical 5-aminosalicylate, corticosteroid therapy, or oral immunomodulator therapy.
  • History of non-inflammatory disease of the pouch: decreased pouch compliance, irritable pouch syndrome, afferent or efferent limb obstruction
  • Isolated cuffitis. Patients who have active pouchitis as the predominant condition, but also have cuffitis may be enrolled.
  • Strictures of the pouch inlet or outlet
  • Ileal pouch patients with familial adenomatous polyposis
  • History of lactose intolerance
  • Known celiac disease
  • Primary sclerosing cholangitis (PSC) with or without liver transplant; PSC with or without Actigall or Urso therapy
  • Uncontrolled systemic diseases
  • Needing oral or topical steroid treatment or 5-ASA agents
  • Other major physical or major psychiatric illness within the last 6 months that in the opinion of the investigator would affect the patient's ability to complete the trial
  • Active use of cholestyramine
  • Active use of NSAIDs or aspirin
  • Women who are pregnant, breast feeding, or planning to become pregnant during the study
  • Patients who are on therapy of 5-ASA at the entry of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00583076

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Ocera Therapeutics
Investigators
Principal Investigator: Bo Shen, MD Clevland Clinic
  More Information

Publications:
Dhillon S; Loftus EV; Tremaine WJ; Jewell DA; Harmsen WS; Zinsmeister AR; Melton LJ; Pemberton H; Wolff BG; Dozois EJ; Cima RR; Larson DW; Sandborn WJ. The natural history of surgery for ulcerative colitis in a population based cohort from Olmsted County, Minnesota. Am J Gastroenterol 2005;100:A819
Shen B; Jiang ZD; Fazio VW; Sherman KK; Rodriguez L; Remzi FH; Bennett A; DuPont HL. Clostridium difficile infection in patients with ileal pouch-anal anastomosis (IPAA). Am J Gastroenterol 2006;Abstract
Sauser P; Fitsher A; Riedel HD; Kleiner H; Kramer W; Stengelin S; Stremmel W; Stiehl A. Reduced transcription of ileal bile acid transporters during chronic ileal inflammation in man. Gastroenterol 2000;118:A4296
Merrett MN; Crotty BJ; Mortensen N; Jewell DP. Ileal pouch dialysate is cytotoxic to I-407 and HT-29 cells: Bile may be the active factor. Gut 1991;32:A1205
Sandborn WJ. Pouchitis: Risk factors, frequency, natural history, classification and public health prospective. In: McLead R; Martin F; Sutherland L; Wallace J; Williams C, eds. Trends in Inflammatory Bowel Disease 1996. Lancaster UK: Kluwer Academic Publishers, 1997:51-63

Responsible Party: Ocera Therapeutics
ClinicalTrials.gov Identifier: NCT00583076     History of Changes
Other Study ID Numbers: 06-908
Study First Received: December 20, 2007
Last Updated: June 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ocera Therapeutics:
Pouchitis
Active Pouchitis
Safety and Efficacy of AST120

Additional relevant MeSH terms:
Pouchitis
Ileitis
Enteritis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Ileal Diseases

ClinicalTrials.gov processed this record on August 26, 2014