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Pilot Comparative Bioavailability Study of 6Mercaptopurine (Delayed Release vs. Purinethol) in Crohns Disease Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00774982
Recruitment Status : Completed
First Posted : October 17, 2008
Last Update Posted : July 17, 2009
Information provided by:
Teva GTC

Brief Summary:

The study is being conducted to evaluate the pharmacokinetic parameters (Cmax, Tmax and AUC) of the new delayed release, lowered dose, 40 mg 6MP test formulation as compared to standard 6MP (100 mg Purinethol) in 12 patients with Crohn's Disease.

The study is being undertaken to prove that the new test formulation is indeed delayed-release and targeted to the ileum, and that the levels of 6MP in the blood following local absorption are lower than that seen following standard Purinethol dosing. This should result in lower, safer mercaptopurine dosing, allowing for uninterrupted treatment with fewer side effects.

Condition or disease Intervention/treatment Phase
Crohns Disease Drug: Delayed Release 6 mercaptopurine Drug: 6 Mercaptopurine Phase 1

Detailed Description:

A new delayed release, faster-disintegrating, lower dose oral formulation of 6 mercaptopurine for targeted delivery to the ileum (the most commonly effected area of Crohns Disease (CD) bowel involvement), was developed and shown to be effective in the three efficacy parameters evaluated in a small group of Crohns Disease patients. Twelve weeks of daily treatment with once-nightly dosing of 40 mg local 6MP resulted in: (1) inducing clinical remission (CDAI scores below 150 as early as weeks 2 and 4), (2) effecting local mucosal healing (as evidenced by lowered CDEIS scores and descriptive conolonoscopy reports) and (3) reducing systemic immunological scores (lowered IFN-gamma Elispot levels).

The current study is being undertaken to confirm, via pharmacokinetic profiles (Cmax, AUC and Tmax), the underlying premises of the above-noted clinical feasibility study. This PK study is being conducted to establish that (1) The delayed release test formulation delivers drug distally to the lower intestine and (2) The delayed release test formulation has the potential for reduced systemic toxicity. The first aspect will be established by comparing the Tmax of the delayed release test formulation vs. oral Purinethol, while the second aspect will be established by comparing the Cmax and AUC of the 40 mg test dose vs. standard 100 mg Purinethol. It is anticipated that the delayed release test formulation will exhibit a later Tmax and reduced Cmax and AUC as compared to reference Purinethol.

Additionally, immunology testing to measure the effect of the new 6MP formulation on immunological FACS analysis will be performed on peripheral blood lymphocytes at 0, 12 and 24 hours post-dosing of each formualtion. Lymphocytes will be tested for surface marker expression (ex: CD3, CD4, CD8, CD25, NKT, etc.), with anticipated results a greater lowering of immune parameters after even 1 dose of 40 mg delayed release test drug, as compared to 100 mg Purinethol.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Official Title: Pilot, Randomized, Open-Label, Two-Way Crossover Comparative Bioavailability Study of 40 mg Delayed Release Oral 6Mercaptopurine Versus 100 mg Purinethol in Patients With Crohns Disease
Study Start Date : December 2008
Actual Primary Completion Date : February 2009
Actual Study Completion Date : February 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: 1 6MP Test Formulation
1 x 40 mg Oral Tablet, 6 MP Delayed Release Test Formulation, for targeted ileal delivery
Drug: Delayed Release 6 mercaptopurine
oral tablet, 1 x 40 mg Delayed Release 6MP tablet, single-dose
Other Name: Administration 1 (A): 1 x 40 mg Delayed Release 6MP TEST

Active Comparator: 2. 6MP Reference Formulation
2 x 50 mg oral tablet, PURINETHOL
Drug: 6 Mercaptopurine
Oral Tablet, 2 x 50 mg 6MP Reference, single-dose
Other Name: Administration 2 (B): 2 x 50 mg Purinethol REFERENCE

Primary Outcome Measures :
  1. PK parameters: AUC, Cmax and Tmax [ Time Frame: Following single dose of test or reference drug ]

Secondary Outcome Measures :
  1. FACS analysis of peripheral blood lymphocytes following single dose of test vs. reference formulation [ Time Frame: Comparison of values from blood collected at 0, 12 and 24 hours post-dose ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 12 male and non-pregnant females, aged 18-50 years, with Crohns Disease (CDAI up to 200), non-smoking.

Crohns Disease diagnosis via colonoscopy with biopsy within the past 12 years No CD medications allowed during study other than 5-ASA and symptomatic relief (anti-diarrheals) Screening lab tests: HGB>= 8.5 g/dl, platelets >= 100,000/mm3, WBC: 3500-12000/mm3, serum albumin above 2.5 g/dl, amylase, lipase and total bilirubin within normal limits; ALT, AST, alkaline phosphatase up to 1.5 x normal limits

Exclusion Criteria:

  • No more than 2 bowel movements/24 hour period in week prior to screening No patients on methotrexate, cyclosporine, or other anti-TNF alpha, or anti-neoplastics within 3 months of study start NO fistulizing CD or isolated small bowle CD No symptomatic stenosis or ileal strictures,or x-ray evidnece of fibrosed bowel

Information from the National Library of Medicine

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 identifier (NCT number): NCT00774982

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Hadassah Medical Center
Jerusalem, Israel
Sponsors and Collaborators
Teva GTC
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Principal Investigator: Yaron Ilan, MD Hadassah Medical Center
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Responsible Party: Prof. Yaron Ilan, Hadasssah Medical Center Identifier: NCT00774982    
Other Study ID Numbers: C1/13/6MP-02
First Posted: October 17, 2008    Key Record Dates
Last Update Posted: July 17, 2009
Last Verified: July 2009
Keywords provided by Teva GTC:
Crohns Disease
Local Targeted Delivery to the Ileum
Delayed Release
Immunology Measurements
Pharmacokinetics in Crohns Disease Patients
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors