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

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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: 4-Aminosalicylic acid
* Drug: PASER placebo granules


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>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<br>* 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<br>* Other names: NDC 49938-107-04;|
| Placebo Comparator: P<br>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<br>* Oral granules administered administered as one packet three times daily for two weeks followed by one packet two times daily for two weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Acute Flare, Mild to moderate Crohn's Disease, Ileocecal distribution