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

NCT01094613 | Terminated Phase 1

• 1 other identifier: Protocol C2/13/DR-6MP-02
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 11

Brief 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

Conditions

Crohn's Disease

Keywords

Crohn's Disease; Delayed Release; Targeted Ileal Delivery

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with clinical response at study end

  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

  12 weeks

Secondary Outcomes (1)

• Time to clinical response

  Week 2, 4, 6, 8 or 12

Study Arms (2)

Delayed Release 6MP

EXPERIMENTAL

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

Purinethol

ACTIVE COMPARATOR

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

Interventions

Delayed Release 6 mercaptopurine DRUG

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.

Also known as: Delayed Release 6 MP tablet (80 mg)

Delayed Release 6MP

6 Mercaptopurine DRUG

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.

Also known as: Purinethol

Purinethol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or (non-pregnant) female, 18-75 years (incl) at screen.
• Diagnosed w/CD, appropriately documented/supported by endoscopy or radiology.
• W/ moderately active CD, w/ screen CDAI score 220-450 (inclusive)
• Screen lab tests:
• HGB \>/= 8.5 g/dL,
• Platelets \>/= 100,000/ mm³
• WBC \>/= 3500 mm³
• Serum albumin \> 2.5 g/dL
• ALT, AST, ALK Phos, GGTP,. total and direct bilirubin \< 2xULN
• Subjects may be on stable (for at least 2 wks prior screen) 5-ASA, chronic antibiotics or low-dose oral steroids (prednisolone-up to 15 mg daily; budesonide-up to 6 mg daily) and remain on the drug at that dose throughout the study
• Willing and able to provide written ICF.

You may not qualify if:

• W/ ulcerative colitis or w/ diagnosis of indeterminate colitis.
• W/ previous bowel resection due to CD resulting in clinically significant Short Bowel Syndrome.
• W/ fistulizing CD w/ clinic or radiologic evidence of abscess.
• W/ clinically significant GI obstructive symptoms or x-ray evidence of fibrosed bowel.
• W/ screen stool culture + for enteric pathogens (Salmonella, Shigella, Campylobacter) or Clostridium difficile toxin assay.
• W/ hx of persistent intestinal obstruction, bowel perforation, uncontrolled GI bleed,abdominal abscess,infection or toxic megacolon.
• W/ hx of GI tract malignancy or IBD-associated malignant intestinal changes.
• W/ surgery/major procedure in 4 weeks prior to 1st study dose.
• Receiving elemental diet or parenteral nutrition.
• W/ current signs/symptoms of clinically significant/unstable med/surg condition that precludes safe/complete study participation, determined by med history, PE, ECG, lab tests or imaging. Such conditions may include severe, progressive or uncontrolled renal, metabolic, hepatic, hematologic, endocrine, pulmonary, cardiovascular, psychiatric, neurologic, cerebral or autoimmune disease.
• W/ currently known malignancy/pre-malignant lesions/hx of malignancy w/in past 5 years, excl basal cell carcinoma.
• W/ hx of coagulopathy.
• W/ porphyria as it may interfere w/ assessment of CD abdominal pain.
• W/ hx of previous thiopurine failure resulting in serious AE (ex: severe pancreatitis, leucopenia, hepatoxicity or bone marrow suppression) so as to preclude addtl tx w/ 6MP at any dose
• Taking w/in 6 months prior to 1st study dose (+during study) Active vaccinations (live attenuated bacterial/viral pathogens)

Sponsors & Collaborators

• Teva GTC: lead

Study Sites (11)

Ha'emek Medical Center

Afula, Israel

Location

Bnai Zion Hospital

Haifa, Israel

Location

Rambam Medical Center

Haifa, Israel

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Shaarei Tzedek Medical Center

Jerusalem, Israel

Location

Meir Medical Center

Kfar Saba, Israel

Location

Holy Family Hospital

Nazareth, Israel

Location

Kaplan Medical Center

Rehovot, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Sheba Medical Center

Tel Litwinsky, Israel

Location

Assaf Harofeh

Ẕerifin, Israel

Location

Related Links

• Previous pilot studies (proof of concept efficacy and pk studies) conducted on the DR6MP tablet

MeSH Terms

Conditions

Crohn Disease

Interventions

Mercaptopurine

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Yaron Ilan, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2010
• First Posted: March 29, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 7, 2013

Record last verified: 2013-03

Locations

IL (11)