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

Condition(s) targeted: Crohn's Disease

Intervention: 4-Aminosalicylic acid (Drug); PASER placebo granules (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Jacobus Pharmaceutical

Official(s) and/or principal investigator(s):
David P. Jacobus, MD, Study Chair, Affiliation: Jacobus Pharmaceutical
Kathy L. Ales, MD, Study Director, Affiliation: Jacobus Pharmaceutical
Daniel Present, MD, Principal Investigator, Affiliation: Mount Sinai School of Medicine
Stephen B. Hanauer, MD, Principal Investigator, Affiliation: University of Chicago Hospitals
John Hanson, MD, Principal Investigator, Affiliation: Charlotte Gastroenterology & Hepatology, PLLC
Iris Dotan, MD, Principal Investigator, Affiliation: Tel-Aviv Sourasky Medical Center
Rami Eliakim, MD, Principal Investigator, Affiliation: Rambam Health Care Campus

Overall contact:
Kathy L. Ales, MD, Phone: 609-921-7447, Ext: 238, Email: kathy.ales@verizon.net

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Response, as defined by a reduction of the CDAI score of >70 points by 4 weeks compared with baseline

Secondary outcome:

Rate of remission as defined by the decrease in CDAI > 100 points and total CDAI < 150 by 4 weeks

Rate of response as defined by a reduction in HBI to less than 5 by 4 weeks

Rate of remission as defined by the decrease in HBI to less than 3 by 4 weeks

Time to response and/or remission including time to change in HBI, according to elements of the daily patient diary

Increase in IBDQ to greater than 170 and the time to score above 170

The change from baseline in the patient's general sense of disease activity as recorded in the individual daily diary

Absence of night time stools, if they were present on entry, and time to disappearance

Time to normalization of all other components in the diary

Change in Hgb, ESR, CRP, platelet count, calprotectin from baseline and time to normalization

Change in global physician assessment of disease activity from baseline to study completion

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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

Kathy L. Ales, MD, Phone: 609-921-7447, Ext: 238, Email: kathy.ales@verizon.net

Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239, Israel; Recruiting
Sara Pel, Phone: 052-4266605, Email: sarap@tasmc.health.gov.il
Iris Dotan, MD, Phone: 972-3-697-3970, Email: irisd@tasmc.health.gov.il
Olga Barkay, MD, Sub-Investigator
Stuart A. Becker, MD, Sub-Investigator
Roy Dekel, MD, Sub-Investigator
Roman Grenshpon, MD, Sub-Investigator
Yulia Kovalev, MD, Sub-Investigator
Alaa Melhem, MD, Sub-Investigator
Guy Rosner, MD, Sub-Investigator
Beni Shpak, MD, Sub-Investigator
Iris Dotan, MD, Principal Investigator

Rambam Medical Center, Haifa 31096, Israel; Recruiting
Zahava Danieli, RN, Phone: 50-2062233, Email: z_danieli@rambam.health.gov.il
Rami Eliakim, MD, Phone: 04-854-3784, Email: r_eliakim@rambam.health.gov.il
Rami Eliakim, MD, Principal Investigator
Irit Chermesh, MD, Sub-Investigator
Alain Suissa, MD, Sub-Investigator
Margarita Brun, MD, Sub-Investigator
Kamel Yassin, MD, Sub-Investigator

The University of Chicago, Chicago, Illinois 60637, United States; Recruiting
Todd Miodek, Phone: 773-702-5382, Email: tmiodek@medicine.bsd.uchicago.edu
Stephen B. Hanauer, MD, Phone: 773-834-7308
Russel D. Cohen, MD, Sub-Investigator
Ira Hanan, MD, Sub-Investigator
Sunanda V. Kane, MD, Sub-Investigator
David T. Rubin, MD, Sub-Investigator
Stephen B. Hanauer, MD, Principal Investigator
Laura E Harrell, M.D., Sub-Investigator
Marc Schwatrz, M.D., Sub-Investigator
Wallene Yang, M.D., Sub-Investigator
Nancy McGreal, M.D., Sub-Investigator
Andrew Aronsohn, MD, Sub-Investigator
Sukanya Subramanian, M.D., Sub-Investigator
Jared Hossack, M.D., Sub-Investigator
Timothy Zisman, M.D., Sub-Investigator

Mount Sinai School of Medicine IBD Research Center, New York, New York 10028, United States; Recruiting
Patrycja Mysliwiec, CRC, Phone: 212-249-1039, Email: patty.mysliwiec@ibdresearch.com
Daniel H. Present, MD, Principal Investigator
James Marion, MD, Sub-Investigator
Adam Steinlauf, MD, Sub-Investigator

Charlotte Gastroenterology and Hepatology, PLLC, Charlotte, North Carolina 28207, United States; Recruiting
Lori Sell, BSN, Phone: 704-375-9485, Email: research@charlottegastro.com
John S. Hanson, MD, Phone: 704-375-9485
Scott A. Brotze, MD, Sub-Investigator
Lauren I. Browne, MD, Sub-Investigator
Thomas A. Carr, MD, Sub-Investigator
Sam R. Fulp, MD, Sub-Investigator
Thomas J. Gavigan, MD, Sub-Investigator
Stephen A. Josephson, MD, Sub-Investigator
Dennis D. Kokenes, MD, Sub-Investigator
Sanjib P. Mohanty, MD, Sub-Investigator
John H. Moore, III, MD, Sub-Investigator
Simon S. Prendiville, MD, Sub-Investigator
Thomas A. Roberts, Jr., MD, Sub-Investigator
John Gardiner R. Roddey, Jr., MD, Sub-Investigator
Robert J. Schmitz, MD, Sub-Investigator
David G. Scholz, MD, Sub-Investigator
James L. Toussaint, MD, Sub-Investigator
Thomas E. Werth, MD, Sub-Investigator
John S. Hanson, MD, Principal Investigator

Starting date: January 2007
Ending date: January 2011
Last updated: July 1, 2008