NCT01094613

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

MultiCTR Randomized Double-Blind Double-Dummy Study to Evaluate Clinical Efficacy/Safety of DR 6MP for Targeted Ileal Delivery vs Purinethol in Patients w/Moderately Active Crohn's Disease

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: Teva GTC · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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 (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

Detailed description

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 new formulation 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 mg) will be tested to ascertain if presumably higher local concentrations at the disease site can evince a more robust clinical effect.

Conditions

• Crohn's Disease

Interventions

Type	Name	Description
DRUG	Delayed Release 6 mercaptopurine	Delayed Release oral tablet for ileal drug delivery, 80 mg, once nightly before bedtime, for 12 weeks. Since the study drug must be blinded, patients randomized to this arm will receive the following: 80 mg DR-6MP: 2 active 40 mg DR-6MP tablets.
DRUG	6 Mercaptopurine	Oral tablet(s) to be administered once daily in the AM, for 12 weeks.Purinethol is available only as a 50 mg tablet; patients randomized to this arm will receive varying doses (dependent on baseline body weight and AE profile) throughout the study;and study drug to be blinded. Therefore, patients randomized to this arm to receive combination active Purinethol/comparable placebo. For ex: 50 mg Purinethol= 1 active 50 mg tablet, 2 comparable placebo tablets; 100 mg Purinethol = 2 active 50 mg tablets, 1 placebo tablet; 150 mg Purinethol = 3 active 50 mg tablets. Patients receiving 75 mg or 125 mg will receive alternating daily doses of 50 and 100 mg, or 100 and 150 mg, respectively, to arrive at a weekly average dose of 75 mg or 125 mg.

Timeline

• Start date: 2010-11-01
• Primary completion: 2012-12-01
• Completion: 2012-12-01
• First posted: 2010-03-29
• Last updated: 2013-03-07

Locations

11 sites across 1 country: Israel