Multicenter Clinical Efficacy and Safety Study of Delayed Release 6MP in Crohn's Disease

Exclusion Criteria

• •1. W/ ulcerative colitis or w/ diagnosis of indeterminate colitis.
• •2. W/ previous bowel resection due to CD resulting in clinically significant Short Bowel Syndrome.
• •3. W/ fistulizing CD w/ clinic or radiologic evidence of abscess.
• •4. W/ clinically significant GI obstructive symptoms or x-ray evidence of fibrosed bowel.
• •5. W/ screen stool culture + for enteric pathogens (Salmonella, Shigella, Campylobacter) or Clostridium difficile toxin assay.
• •6. W/ hx of persistent intestinal obstruction, bowel perforation, uncontrolled GI bleed,abdominal abscess,infection or toxic megacolon.
• •7. W/ hx of GI tract malignancy or IBD-associated malignant intestinal changes.
• •8. W/ surgery/major procedure in 4 weeks prior to 1st study dose.
• •9. Receiving elemental diet or parenteral nutrition.
• •10. W/ current signs/symptoms of clinically significant/unstable med/surg condition that precludes safe/complete study participation, determined by med history, PE, ECG, lab tests or imaging. Such conditions may include severe, progressive or uncontrolled renal, metabolic, hepatic, hematologic, endocrine, pulmonary, cardiovascular, psychiatric, neurologic, cerebral or autoimmune disease.
• •11. W/ serious infections, such as hepatitis, pneumonia, pyelonephritis w/in 12 weeks prior to 1st study dose. Less serious infections such as acute UR tract infections or uncomplicated UT infection not considered exclusions - at discretion of PI.
• •12. W/ currently known malignancy/pre-malignant lesions/hx of malignancy w/in past 5 years, excl basal cell carcinoma.
• •13. W/ hx of coagulopathy.
• •14. W/ porphyria as it may interfere w/ assessment of CD abdominal pain.
• •15. W/ hx of previous thiopurine failure resulting in serious AE (ex: severe pancreatitis, leucopenia, hepatoxicity or bone marrow suppression) so as to preclude addtl tx w/ 6MP at any dose
• •16. Taking w/in 6 months prior to 1st study dose (+during study) Active vaccinations (live attenuated bacterial/viral pathogens)
• •17. Taking w/in 6 weeks prior to 1st study dose (+ during study):
• •* Anti-TNFα (infliximab, etanercept, adalimumab)
• •* Anti-integrin (natalizumab)
• •* Anti-neoplastics, incl methotrexate, daunorubicin hydrochloride
• •18. Taking w/in 4 weeks prior to 1st study dose (+ during study):
• •* Immunosuppressants such as AZA, 6-MP (i.e., other than 6MP drug assigned during study), cyclosporine, tacrolimus, mycophenolate mofetil or thalidomide.
• •* Antibiotics or oral/IV corticosteroids (other than oral prednisolone allowed during study as rescue therapy as per protocol).
• •* Tx w/ drugs known to induce/inhibit endogenous hepatic drug metabolism such as barbiturates, phenothiazines, cimetidine, carbamazepine etc.
• •* Anti-coagulant therapy such as: heparin, warfarin, acenocoumarol.
• •* Medications that induce blood dyscrasias or w/ potential for immune dysfunction, bone marrow depression and/or symptoms of CD (diarrhea, abdominal pain).
• •* Vaccinations involving inactivated forms of pathogens or purified antigenic proteins (Note: passive immunization involving antibody inoculations permitted at any time)
• •19. Tx w/in 2 wks prior to 1st study dose (+ during study) IV or oral steroids (prednisolone or budesonide) Antibiotics
• •Note: 2 impt exceptions (a) Subjects oral steroid or antibiotic dependent with active CD (CDAI 220-450)in spite of these txs, may remain on tx provided on stable (\>=2wks at screen)dose and remain at that dose throughout study (b) Subjects who require steroid-rescue during study
• •20. Taking w/in 7 days prior to 1st study dose (+ during study):
• •* Anticholinergic or other drugs known to affect GI motility.
• •* Allopurinol
• •* Proton pump inhibitors or other drugs affecting gastric acidity
• •21. W/body weight below 42.5 kg.
• •22. Pregnant/nursing at screen, or intend to be during study.
• •23. Women of childbearing potential not practicing acceptable method of birth control \[acceptable methods: surgical sterilization, IUD, contraceptive (oral, patch, or long-acting injectable), partner's vasectomy, double-protection method (condom or diaphragm w/ spermicide) or abstinence\].
• •24. W/ current/hx of drug and/or alcohol abuse.
• •25. Largely or wholly bed-ridden and w/ little capacity for self-care.
• •26. W/ known allergy or hypersensitivity to 6-MP or any inactive component of study drug (ex: lactose intolerant).
• •27. Participated in other clinical trial using investigational drugs w/in 12 weeks prior to 1st study dose.
• •28. W/ planned elective surgery or hospitalization during study (that may interfere w/ study compliance/outcome).
• •29. W/inability to communicate well w/investigators/staff (i.e., language problem, poor mental development or impaired cerebral function).
• •30. Unavailable for trial duration, unable to comply w/schedule, likely to be noncompliant, or felt unsuitable by PI for any other reason.