Pilot Comparative Bioavailability Study of 6Mercaptopurine (Delayed Release vs. Purinethol) in Crohns Disease Patients
Condition: Crohns Disease
MeSH terms: Crohn Disease
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): Delayed Release 6 mercaptopurine; 6 Mercaptopurine
Intervention type(s): Drug; Drug
Intervention description(s): oral tablet, 1 x 40 mg Delayed Release 6MP tablet, single-dose; Oral Tablet, 2 x 50 mg 6MP Reference, single-dose
Other intervention name(s): Administration 1 (A): 1 x 40 mg Delayed Release 6MP TEST; Administration 2 (B): 2 x 50 mg Purinethol REFERENCE
Intervention MeSH terms: Mercaptopurine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Keywords: Crohns Disease; Pharmacokinetics; Local Targeted Delivery to the Ileum; Delayed Release; Immunology Measurements; Pharmacokinetics in Crohns Disease Patients