Azathioprine & Allopurinol in Inflammatory Bowel Disease Patients

University of Zurich (UZH)

Status and phase

Completed

Phase 1

Conditions

Inflammatory Bowel Disease

Treatments

Drug: Azathioprine / Allopurinol

Study type

Interventional

Funder types

Other

Identifiers

NCT00849368

PHA-08-AZA/ALLO-01

Details and patient eligibility

About

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

Enrollment

6 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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