Clinical trial NCT00417690: High Dose Oral 4-Aminosalicylic Acid (PASER®) to Control Acute Flares of Mild to Moderate 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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Crohn's Disease
Acute Flare
Mild to moderate Crohn's Disease
Ileocecal distribution
Lead sponsor: Jacobus Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2007-01-04
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Response, as defined by a reduction of the CDAI score of >70 points by 4 weeks compared with baseline
timeFrame: 4 weeks
Secondary outcomes:
measure: Rate of remission as defined by the decrease in CDAI > 100 points and total CDAI < 150 by 4 weeks
timeFrame: 4 weeks
measure: Rate of response as defined by a reduction in HBI to less than 5 by 4 weeks
timeFrame: 4 weeks
measure: Rate of remission as defined by the decrease in HBI to less than 3 by 4 weeks
timeFrame: 4 weeks
measure: Time to response and/or remission including time to change in HBI, according to elements of the daily patient diary
timeFrame: up to 4 weeks
measure: Increase in IBDQ to greater than 170 and the time to score above 170
timeFrame: 4 weeks
measure: The change from baseline in the patient's general sense of disease activity as recorded in the individual daily diary
timeFrame: up to 4 weeks
measure: Absence of night time stools, if they were present on entry, and time to disappearance
timeFrame: up to 4 weeks
measure: Time to normalization of all other components in the diary
timeFrame: up to 4 weeks
measure: Change in Hgb, ESR, CRP, platelet count, calprotectin from baseline and time to normalization
timeFrame: 2 weeks and 4 weeks
measure: Change in global physician assessment of disease activity from baseline to study completion
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: New York
country: United States
facility: Mount Sinai School of Medicine IBD Research Center
state: New York
city: Charlotte
country: United States
facility: Charlotte Gastroenterology and Hepatology, PLLC
state: North Carolina
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
Study officials:
affiliation: Jacobus Pharmaceutical
name: David P. Jacobus, MD
role: STUDY_CHAIR
affiliation: Jacobus Pharmaceutical
name: Kathy L. Ales, MD
role: STUDY_DIRECTOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Daniel Present, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago Hospitals
name: Stephen B. Hanauer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charlotte Gastroenterology & Hepatology, PLLC
name: John Hanson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tel-Aviv Sourasky Medical Center
name: Iris Dotan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rambam Health Care Campus
name: Rami Eliakim, MD
role: PRINCIPAL_INVESTIGATOR
References: