Title
High Dose Oral 4-Aminosalicylic Acid (PASER®) to Control Acute Flares of Mild to Moderate Crohn's Disease in Children
A Prospective Randomized Double-Blind Study of PASER® in the Management of Patients Experiencing an Acute Flare of Crohn's Disease
Phase
Phase 2Lead Sponsor
Jacobus PharmaceuticalStudy Type
InterventionalStatus
Terminated Results PostedIndication/Condition
Crohn's DiseaseIntervention/Treatment
aminosalicylic acid ...Study Participants
2The purpose of this 4 week study is to determine whether PASER®, an approved delayed-release oral formulation of 4-aminosalicylic acid, in doses of 50 milligrams per kilogram three times daily for 2 weeks followed by 50 milligrams per kilogram twice daily for 2 weeks, will resolve an acute flare of ileocecal Crohn's disease.
Eligible pediatric patients with acute flares of ileocecal Crohn's disease will be randomized to receive either PASER®, an approved delayed-release oral formulation of 4-aminosalicylic acid, in doses of 50 milligrams per kilogram three times daily for 2 weeks followed by 50 milligrams per kilogram twice daily for 2 weeks, or an identical-appearing placebo preparation.
Patients will be required to maintain a daily diary and to return at 2 weeks for blood and stool tests. At the four week mark, patients will return for clinical evaluation, global assessment of disease activity and change in disease activity, as well as additional laboratory tests.
Granules for oral administration will be administered as a volume equivalent to 50 mg/kg of 4-aminosalicylic acid three times daily for 2 weeks followed by 2 times daily for 2 weeks in the active arm or a comparable volume in the placebo arm
4-Aminosalicylic acid extended release granules (as volume equivalent of active product), 50 mg/kg orally three times daily for two weeks followed by (as volume equivalent) 50 mg/kg orally two times daily for 2 weeks
Placebo granules identical in appearance to the active arm (as volume equivalent of active product), 0 mg/kg orally three times daily for two weeks followed by (as volume equivalent) 0 mg/kg orally two times daily for 2 weeks
Inclusion Criteria: Age less than 18 years Crohn's disease predominantly involving 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, budesonide Corticosteroids within 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 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 New fistulization as part of the acute flare or increased activity in chronic fistula(e) as part of the acute flare Hypersensitivity to 4-ASA or any components of PASER® Pregnancy or breast-feeding Failure of a woman of child-bearing potential to agree to use adequate contraception for the 4 week period of the trial, if sexually active Severe renal or hepatic disease (i.e., more than 3 times upper limit of normal) or a WBC < 3,000 during the preceding three months
| Event Type | Organ System | Event Term | Active | Placebo |
|---|
Reduction in the Modified Crohn's Disease Activity Index (mCDAI) score of >70 points by 4 weeks after randomization compared with baseline
Rate of remission was defined by a decrease in modified Crohn's Disease Activity Index (mCDAI) > 100 points and total mCDAI < 150 by 4 weeks
