Multicenter Clinical Efficacy and Safety Study of Delayed Release 6MP in Crohn's Disease
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|ClinicalTrials.gov Identifier: NCT01094613|
Recruitment Status : Terminated (Sponsor withdrew support of study due to reorganization and project prioritization)
First Posted : March 29, 2010
Last Update Posted : March 7, 2013
|Condition or disease||Intervention/treatment||Phase|
|Crohn's Disease||Drug: Delayed Release 6 mercaptopurine Drug: 6 Mercaptopurine||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||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|
|Study Start Date :||November 2010|
|Actual Primary Completion Date :||December 2012|
|Actual Study Completion Date :||December 2012|
Experimental: Delayed Release 6MP
6 Mercaptopurine delayed release oral tablet for targeted ileal delivery, to be administered once nightly before bedtime, for 12 weeks.
The dose is 2 x 40 mg DR-6MP (total dose, 80 mg DR-6MP).
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.
Other Name: Delayed Release 6 MP tablet (80 mg)
Active Comparator: Purinethol
6 Mercaptopurine Tablet (50 mg) administered orally, at doses of 1-1.5 mg/kg body weight, daily for 12 weeks. Individual patient doses range from 50 mg to 150 mg, including 75, 100 and 125 mg daily, as per patient weight at baseline, and then are up-titrated to clinical efficacy at two week intervals, as needed. Doses may be down-titrated as well if occurrences of AE's warrant dose reduction.
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.
Other Name: Purinethol
- Proportion of subjects with clinical response at study end [ Time Frame: 12 weeks ]Clinical response is defined as a reduction in CDAI score (Crohn's Disease Activity Index) by 100 points from baseline, or remission (CDAI score <150),even if it is achieved with reduction of CDAI score of less than 100 points from baseline
- Time to clinical response [ Time Frame: Week 2, 4, 6, 8 or 12 ]Although the primary outcome is to assess the proportion of patients with clinical response at Week 12, we are also interested to see how early during treatment (i.e., between weeks 2 and 12), was this clinical response actually achieved for each treatment group, and if it was maintained until the end of the study (week 12)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01094613
|Ha'emek Medical Center|
|Bnai Zion Hospital|
|Rambam Medical Center|
|Hadassah Medical Center|
|Shaarei Tzedek Medical Center|
|Meir Medical Center|
|Kfar Saba, Israel|
|Holy Family Hospital|
|Kaplan Medical Center|
|Tel Aviv Sourasky Medical Center|
|Tel Aviv, Israel|
|Sheba Medical Center|
|Tel Hashomer, Israel|
|Principal Investigator:||Yaron Ilan, MD||Hadassah Medical Center|