Azathioprine & Allopurinol in Inflammatory Bowel Disease Patients

Sponsor

University of Zurich (Other)

Overall Status

Completed

CT.gov ID

NCT00849368

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Disease	Drug: Azathioprine / Allopurinol	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dose-effect Relationship Between Allopurinol, Azathioprine and 6-thioguanine Nucleotide Levels (6-TGN) in Inflammatory Bowel Disease Patients.

Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azathioprine / Allopurinol Single arm study: Dose escalations as described.	Drug: 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 Other Names: Azathioprine: Imurek (R) 50 mg and 25 mg tablets Allopurinol: Mephanol (R) 100 mg tablets

Arm

Intervention/Treatment

Experimental: Azathioprine / Allopurinol

Single arm study: Dose escalations as described.

Drug: 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

Other Names:

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

Allopurinol: Mephanol (R) 100 mg tablets

Outcome Measures

Primary Outcome Measures

Pharmacokinetics: Quantification of trough concentrations of 6-TGN and 6-MMPN in erythrocytes using HPLC at each dose level. [three times per cycle]

Secondary Outcome Measures

Dose escalation: Assessment of the percentage of patients who are in the desired therapeutic range on day 23-25 and on day 26-28 of each dose level. [once per cycle]
Efficacy: Change in disease activity score in relationship to the dose level attained. [once per cycle]
TPMT activity assessment [once per cycle]
Safety and Tolerability: Medical history, adverse events and well-being; laboratory screen, physical examination, vital functions: blood pressure, heart rate, body temperature [screening, up to three times per cycle, follow-up]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Division of Clinical Pharmacology and Toxicology, University Hospital Zurich	Zurich		Switzerland	CH-8091

Sponsors and Collaborators

University of Zurich

Investigators

Study Director: 01 Studienregister MasterAdmins, UniversitaetsSpital Zuerich
Principal Investigator: Alexander Jetter, MD, Division of Clinical Pharmacology and Toxicology, University Hospital Zürich, 8091 Zürich, Switzerland