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The study is designed to evaluate the clinical efficacy and safety of daily treatment for 12 weeks of oral administration of a delayed release, locally delivered 6MP (mercaptopurine) drug at two doses (40 and 80 mg), as compared to standard Purinethol (at a dose of 1-1.5 mg/kg/body weight), in alleviating the clinical, immunological and mucosal signs and symptoms of moderately active Crohn's Disease
Crohn's Disease (CD) therapy is aimed at reducing inflammation via induction of remission after a flare-up and maintenance of the remission for as long as possible. Therapies commonly used for inducing remission are steroids and anti-TNF-a. Standard 6MP, on the other hand, has a slow onset of action and requires several months of administration before its therapeutic effects become apparent. Therefore, 6MP is typically used as maintenance therapy, rather than for remission. Furthermore, serious AE's associated wtih 6MP include leucopenia, hepatoxicity, pancreatitis and bone marrow suppression, requiring lowering of dose or treatment discontinuation.
The Teva DR-6MP project was designed to evaluate a new oral 6MP formulation that would address these limitations. The slow action of standard 6MP, precluding its use as a treatment for induction of remission, would be offset by a faster-disintegrating, more soluble formulation with an enteric coating for targeted ileal delivery. This lower dose (40 mg), designed to open at the terminal ileum, the most commonly affected area of CD bowel involvement, could deliver higher effective local concentrations of drug to the site most affected by CD, stimulating an effective local immunological response, resulting in a cascade of widespread immunological activity, evoking an induction of remission. The safety of standard 6MP would be improved upon by the fact that negligible levels of the DR-6MP formulation have been observed in the plasma, obviating the toxicities associated with systemic 6MP. Moreover, since the DR-6MP dose is fixed and not subject to patient weight, nor potentially, side-effects, the dose adjustments required for up-titration to optimal dose, or down-titration due to toxicity, could be avoided.
Previous small, pilot proof-of-concept clinical efficacy and pharmacokinetic studies of the DR-6MP formulation demonstrated the potential for induction of remission, mucosal healing, systemic immunological improvement and lower systemic side-effects.
The current study is designed to repeat the earlier studies under larger, more rigorous conditions in a randomized, double-blind fashion at multiple sites to ascertain if the initial encouraging results could be repeated. Moreover, a higher dose of 6MP (80 vs. 40) will be tested to ascertain if presumably higher local concentrations at the disease site can evince a more robust clinical effect.
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Delayed Release 6 mercaptopurine, 6 Mercaptopurine
Soroka Medical Center
Not yet recruiting
Published on BioPortfolio: 2014-08-27T03:14:57-0400
The study is being undertaken to evaluate whether delayed-release medications, designed to begin to open in the lower intestinal tract, the main site of Crohn's Disease, are more effective...
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An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.
Sulfhydryl analog of INOSINE that inhibits nucleoside transport across erythrocyte plasma membranes, and has immunosuppressive properties. It has been used similarly to MERCAPTOPURINE in the treatment of leukemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p503)
A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.
A condition characterized by persistent or recurrent labial enlargement, ORAL ULCER, and other orofacial manifestations in the absence of identifiable CROHN DISEASE; or SARCOIDOSIS. There is no consensus on whether orofacial granulomatosis is a distinct clinical disorder or an initial presentation of Crohn disease.
An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 18.104.22.168.
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Crohn's Disease (CD)
Crohn’s disease (CD) is a long-term condition that causes inflammation of the lining of the digestive system. Inflammation can affect any part of the digestive system, from the mouth to the back passage, but most commonly occurs in the last s...