Imuran (Azathioprine) Dose-Ranging Study in Crohn's Disease

NCT00098111 | Terminated Phase 3

• 2 other identifiers: FD-R-02555-01Grant # 2555
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to identify an optimal weight based dose of azathioprine that is safe and effective in the treatment of subjects with active Crohn's disease requiring treatment with corticosteroids, and for maintaining remission in those subjects.

Conditions

Crohn's Disease

Keywords

Crohn's disease; inflammatory bowel disease; IMURAN; azathioprine

Outcome Measures

Primary Outcomes (1)

• To identify an optimal weight-based dose of azathioprine for the treatment of active Crohn's disease and for maintaining remission in those subjects.

Secondary Outcomes (5)

• To characterize prospectively the predictive value of erythrocyte thioguanine nucleotide levels for response to azathioprine in who are wild type for the (thiopurine methyltransferase) TPMT gene

• To explore the relationship of 6-thioguanine (TGN) levels to TPMT enzyme activity

• To determine the effect of azathioprine dose upon time to relapse among subjects in remission induced by a course of prednisone

• To prospectively determine the rate of adverse events associated with a range of doses of azathioprine

• To preliminarily identify genetic polymorphisms associated with therapeutic response or toxicity to azathioprine.

Study Arms (3)

Azathioprine 0.5 mg/kg body weight

ACTIVE COMPARATOR

Drug: azathioprine

Azathioprine 2.5 mg/kg body weight

ACTIVE COMPARATOR

Drug: azathioprine

Azathioprine 3.5 mg/kg body weight

ACTIVE COMPARATOR

Drug: azathioprine

Interventions

azathioprine DRUG

Azathioprine 0.5 mg/kg body weight; Azathioprine 2.5 mg/kg body weight; Azathioprine 3.5 mg/kg body weight

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 14 years old, including women of childbearing potential who are not pregnant or nursing at the time of enrollment.
• Body weight between 40 and 100 kg (88-220 lbs), inclusive.
• Subjects diagnosed with Crohn's disease, based upon the criteria of Lennard-Jones, for at least a 3-month period. The date of diagnosis will be the date of the first diagnostic test that confirms the diagnosis of Crohn's disease. Subjects with a diagnosis of less than 3 months may be considered after review of primary diagnostic data by the study safety monitor.
• Need for treatment with oral prednisone, based upon the treating physician's clinical judgment, for active Crohn's disease as indicated by a (Crohn's Disease Activity Index) CDAI between 200 and 450, inclusive; OR Currently being treated with prednisone for at least 4 weeks with a stable dose of 40mg/day or less for at least 2 weeks, or budesonide (Entocort EC) 9 mg/day for at least 4 weeks with a stable dose for at least 4 weeks, and active Crohn's disease as indicated by a CDAI between 200 and 450, inclusive.
• Able to swallow tablets.
• Able to provide written informed consent (subjects ≥ 18 years old) or in the case of a minor provide parental consent along with child assent (subjects 14-17 years old).
• If sexually active, willing to comply with effective contraception during the study; or is abstinent.

You may not qualify if:

• Diagnosis of indeterminate, microscopic, lymphocytic, collagenous, or ulcerative colitis.
• Previous or current therapy with 6-mercaptopurine, azathioprine, thioguanine, methotrexate, cyclosporine, tacrolimus, thalidomide or mycophenolate mofetil.
• Previous or current treatment with infliximab.
• Treatment with narcotic pain medications. (Anti-diarrheal agents such as loperamide and diphenoxylate are permitted, providing that the dose is not increased while on protocol.)
• Subjects with short gut syndrome (defined as requiring oral or parenteral supplemental or total nutrition in order to maintain stable body weight, or more than 100 cm of small bowel resected).
• Subjects with obstructive symptoms or demonstrated stenosis and prestenotic dilatation on barium study.
• Subjects with active infection.
• Subjects with a stoma.
• Subjects with heterozygous or recessive homozygous genotype for TPMT.
• Poor access for peripheral venous phlebotomy.
• History of pancreatitis, except for self-limited episodes from a known cause, such as gallstone pancreatitis.
• White blood cell count (WBC) \<4.5 x 10\^9/L, hemoglobin \<8 gm/dL, Platelets (PLT) \<100,000/mm3 at screening (or within the previous 6 months, if known).
• History of abnormal liver function tests, including aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times upper limit of normal, alkaline phosphatase \>2 times upper limit of normal, total bilirubin \>2.5 mg/dL at screening (or within the previous 6 months, if known).
• Subjects needing treatment with orally administered corticosteroids for the treatment of other medical conditions. Inhaled or dermatologic preparations are acceptable.
• History of HIV infection (if known) or opportunistic infection.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Bruce E Sands, M.D.,M.S.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician

Study Record Dates

• First Submitted: December 3, 2004
• First Posted: December 6, 2004
• Study Start: April 1, 2005
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: February 21, 2014

Record last verified: 2014-02

Locations

US (1)