High Dose Oral 4-Aminosalicylic Acid (PASER®) to Control Acute Flares of Mild to Moderate Crohn's Disease

A Prospective Randomized Double-Blind Study of PASER® in the Management of Patients Experiencing an Acute Flare of Crohn's Disease

The purpose of this 4 week study is to determine whether PASER®, an approved delayed-release oral formulation of 4-aminosalicylic acid, in doses of 4 grams three times daily for 2 weeks followed by 4 grams twice daily for 2 weeks, will resolve an acute flare of ileocecal Crohn's disease.

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: 4-Aminosalicylic acid; Drug: PASER placebo granules

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Tel-Aviv, Israel, 64239
    • Tel-Aviv Sourasky Medical Center
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • New York
    • New York, New York, United States, 10028
      • Mount Sinai School of Medicine IBD Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Gastroenterology and Hepatology, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-65
• Crohn's disease involving predominantly the ileum and/or cecum. The diagnosis must have been established by radiography, endoscopy and/or biopsy (at least 2 of the 3 modalities) with at least one confirmatory test having been performed no more than 36 months before entry. The diagnosis must have been confirmed by at least one gastroenterologist.
• Harvey Bradshaw Index of at least 7
• The onset of the acute flare should have been abrupt, declaring itself over 72 hours, and should have started no more than 4 weeks before study entry. Symptoms relating to the flare should not have diminished or started to improve prior to entry.
• Written informed consent

Exclusion Criteria:

• Concomitant corticosteroids, including budesonide
• Corticosteroids within the previous 2 months
• Cyclosporine, mycophenolate mofetil or experimental drugs during the last three months
• Maintenance infliximab, or infliximab or other biologics in the preceding 3 months
• Change in dose during previous 4 weeks in 5-aminosalicylate, probiotic and/or antibiotic, or in chronic azathioprine, 6-mercaptopurine, or methotrexate
• If currently using azathioprine, 6-mercaptopurine or methotrexate, these must have been used steadily for at least 4 months
• Current experimental drugs or experimental drugs within the last 3 months
• If the severity of the flare has started to decrease spontaneously
• Coexisting diagnosis of primary sclerosing cholangitis,
• Infectious diarrhea,
• Signs of intestinal obstruction or perforation or abscess,
• New fistulization as part of the acute flare or increased activity in chronic fistula(e) as part of the acute flare,
• Increased activity of pre-existing anal or rectal Crohn's disease as part of the flare
• Allergy or sensitivity to salicylates
• Pregnancy or breast-feeding
• Failure of a woman of child-bearing age to agree to use adequate contraception for the 4 week period of the trial, if sexually active
• Severe renal or hepatic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Oral granules administered as one 4 g packet three times daily for two weeks followed by one 4 g packet two times daily for two weeks	Drug: 4-Aminosalicylic acid; Oral granules administered as one 4 g packet three times daily for two weeks followed by one 4 g packet two times daily for two weeks; Other Names: PASER Granules; NDC 49938-107-04
Placebo Comparator: P; One packet of oral granules administered three times daily for 2 weeks followed by one packet two times daily for two weeks	Drug: PASER placebo granules; Oral granules administered administered as one packet three times daily for two weeks followed by one packet two times daily for two weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response, as defined by a reduction of the CDAI score of >70 points by 4 weeks compared with baseline	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of remission as defined by the decrease in CDAI > 100 points and total CDAI < 150 by 4 weeks	4 weeks
Rate of response as defined by a reduction in HBI to less than 5 by 4 weeks	4 weeks
Rate of remission as defined by the decrease in HBI to less than 3 by 4 weeks	4 weeks
Time to response and/or remission including time to change in HBI, according to elements of the daily patient diary	up to 4 weeks
Increase in IBDQ to greater than 170 and the time to score above 170	4 weeks
The change from baseline in the patient's general sense of disease activity as recorded in the individual daily diary	up to 4 weeks
Absence of night time stools, if they were present on entry, and time to disappearance	up to 4 weeks
Time to normalization of all other components in the diary	up to 4 weeks
Change in Hgb, ESR, CRP, platelet count, calprotectin from baseline and time to normalization	2 weeks and 4 weeks
Change in global physician assessment of disease activity from baseline to study completion	4 weeks

Collaborators and Investigators

• Sponsor: Jacobus Pharmaceutical
• Investigators: Study Chair: David P. Jacobus, MD, Jacobus Pharmaceutical; Study Director: Kathy L. Ales, MD, Jacobus Pharmaceutical; Principal Investigator: Daniel Present, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Stephen B. Hanauer, MD, University of Chicago Hospitals; Principal Investigator: John Hanson, MD, Charlotte Gastroenterology & Hepatology, PLLC

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: January 2, 2007
• First Submitted That Met QC Criteria: January 2, 2007
• First Posted (Estimate): January 4, 2007

Study Record Updates

• Last Update Posted (Estimate): October 15, 2008
• Last Update Submitted That Met QC Criteria: October 14, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Crohn's Disease; Mild to moderate Crohn's Disease; Acute Flare; Ileocecal distribution
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Infective Agents; Anti-Bacterial Agents; Antitubercular Agents; Aminosalicylic Acid
• Other Study ID Numbers: PASER-AFC.001