Azathioprine & Allopurinol in Inflammatory Bowel Disease Patients

NCT ID: NCT00849368

Last Updated: 2012-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2011-09-30

Brief Summary

Main Study Objectives:

The study is conducted to

• evaluate the minimal allopurinol and azathioprine doses that, in combination, produce therapeutic 6-TGN levels
• evaluate the safety and tolerability of the different allopurinol/azathioprine dose levels
• assess if concomitant allopurinol affects TPMT activity
• assess the clinical efficacy of concomitant allopurinol-azathioprine therapy in the included patients

Conditions

Inflammatory Bowel Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azathioprine / Allopurinol

Single arm study: Dose escalations as described.

Group Type: EXPERIMENTAL

Azathioprine / Allopurinol

Intervention Type: DRUG

Both drugs are applied orally. A pre-specified dose escalation regimen will be chosen.

Azathioprine: Imurek (R) 50 mg and 25 mg tablets

Allopurinol: Mephanol (R) 100 mg tablets

Interventions

Azathioprine / Allopurinol

Both drugs are applied orally. A pre-specified dose escalation regimen will be chosen.

Azathioprine: Imurek (R) 50 mg and 25 mg tablets

Allopurinol: Mephanol (R) 100 mg tablets

Intervention Type: DRUG

Other Intervention Names

Azathioprine: Imurek (R) 50 mg and 25 mg tablets; Allopurinol: Mephanol (R) 100 mg tablets

Eligibility Criteria

Inclusion Criteria

• Able and willing to give written informed consent before any trial-specific procedures are performed
• Signed informed consent form
• Age 18 to 65 years at study entry
• Body Mass Index 18 - 30 kg/m2
• Confirmed diagnosis of either CROHN's disease or ulcerative colitis prior to study enrollment by combinations of clinical, endoscopic and histologic criteria generally accepted for CD and UC
• Normal TPMT activity > 30 nmol MTG/gHb x h
• Insufficient disease control despite adequate therapy with corticosteroids and/or salicylic acid derivatives, and/or two or more episodes with steroid-requiring disease activity per year, and/or recurrence of disease activity at steroid doses below 15 mg prednisone equivalent, and/or recurrence within 6 weeks after steroid withdrawal.

Exclusion Criteria

• Subjects with confirmed or suspected hypersensitivity towards the study medication
• Contemporaneous participation in any other study
• Females only: pregnancy
• Females only: breast-feeding
• Prior thiopurine therapy
• Current and previous immunosuppressive therapy except corticosteroids (e.g. methotrexate, cyclosporine, mycophenolate mofetil, tacrolimus, infliximab or other TNF-alpha blocker therapy) within 3 months before the first drug intake
• Subjects with any clinically relevant comorbidity beyond the diagnosis of CROHN's disease or ulcerative colitis (as based on extensive medical history, physical examination, vital signs, routine laboratory screen and 12-lead ECG)
• Haemoglobin < 12 g/dl at the screening examination
• Leucocytes < 3 x 10E3/µl at the screening examination
• Lymphocytes < 1.5 x 10E3/µl at the screening examination
• Thrombocytes < 140 x 10E3/µl at the screening examination
• Renal disease (creatinine clearance < 60 ml/min, assessed with MDRD formula), history of serious renal disease
• Liver disease (GGT, alkaline phosphatase, ALAT, ASAT > 2 times the upper limit of normal reference, known or suspected liver cirrhosis)
• Known or suspected malignancies of any kind
• Known or suspected active infections, serious infections in the preceding 3 months
• Active, acute or chronic, or history of, prior hepatitis B infection confirmed by a positive hepatitis B serology (positive HBsAg, Anti-HBc). Patients with a positive hepatitis C screening test (positive anti-HCV). Patients with a positive HIV testing (positive HIV 1 / 2 antibody tests)
• Active varicella zoster infection (chickenpox, shingles)
• Known or suspected symptomatic bowel stenoses or strictures, and patients who had a small bowel resection
• Subjects who are known or suspected not to be capable of understanding and evaluating the information that is given to them as part of the formal information policy (informed consent), in particular regarding the risks and discomfort to which they will be exposed
• Subjects who are known or suspected not to comply with the study directives and / or known or suspected not to be reliable or trustworthy
• Subjects who are not willing to comply with the instructions and duties concerning the subject insurance
• Women of childbearing age and potential who are not willing or capable to use acceptable methods of contraception (oral contraceptives, condoms, diaphragms, intrauterine devices) during the entire study and for up to three months after the end-of-study evaluation.
• Male patients who do not use acceptable barrier methods of contraception (condoms) during the entire course of the study and up to three months after the end-of-study evaluation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Alexander Jetter

PD Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

01 Studienregister MasterAdmins

Role: STUDY_DIRECTOR

UniversitaetsSpital Zuerich

Alexander Jetter, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Clinical Pharmacology and Toxicology, University Hospital Zürich, 8091 Zürich, Switzerland

Locations

Division of Clinical Pharmacology and Toxicology, University Hospital Zurich

Zurich, , Switzerland

Countries

Switzerland

Other Identifiers

PHA-08-AZA/ALLO-01

Identifier Type: -

Identifier Source: org_study_id