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Azathioprine & Allopurinol in Inflammatory Bowel Disease Patients
This study is currently recruiting participants.
Verified by University of Zurich, June 2009
First Received: September 2, 2008   Last Updated: June 2, 2009   History of Changes
Sponsored by: University of Zurich
Information provided by: University of Zurich
ClinicalTrials.gov Identifier: NCT00849368
  Purpose

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 Intervention Phase
Inflammatory Bowel Disease
Drug: Azathioprine / Allopurinol
Phase I

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Pharmacokinetics/Dynamics Study
Official Title: Dose-Effect Relationship Between Allopurinol, Azathioprine and 6-Thioguanine Nucleotide Levels (6-TGN) in Inflammatory Bowel Disease Patients.

Resource links provided by NLM:


Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Pharmacokinetics: Quantification of trough concentrations of 6-TGN and 6-MMPN in erythrocytes using HPLC at each dose level. [ Time Frame: three times per cycle ] [ Designated as safety issue: No ]

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. [ Time Frame: once per cycle ] [ Designated as safety issue: Yes ]
  • Efficacy: Change in disease activity score in relationship to the dose level attained. [ Time Frame: once per cycle ] [ Designated as safety issue: No ]
  • TPMT activity assessment [ Time Frame: once per cycle ] [ Designated as safety issue: No ]
  • Safety and Tolerability: Medical history, adverse events and well-being; laboratory screen, physical examination, vital functions: blood pressure, heart rate, body temperature [ Time Frame: screening, up to three times per cycle, follow-up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: January 2009
Estimated Study Completion Date: April 2010
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Azathioprine / Allopurinol: Experimental
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


  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00849368

Contacts
Contact: 01 Studienregister MasterAdmins +41 (0)44 255 11 11
Contact: Alexander Jetter, MD +41-44-255-9050 alexander.jetter@usz.ch

Locations
Switzerland
Division of Clinical Pharmacology and Toxicology, University Hospital Zurich Recruiting
Zurich, Switzerland, CH-8091
Contact: Alexander Jetter, MD     +41-44-255-9050        
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
  More Information

No publications provided

Responsible Party: Division of Clinical Pharmacology & Toxicology, University Hospital Zürich ( Dr. med. Alexander Jetter, MD )
Study ID Numbers: PHA-08-AZA/ALLO-01
Study First Received: September 2, 2008
Last Updated: June 2, 2009
ClinicalTrials.gov Identifier: NCT00849368     History of Changes
Health Authority: Switzerland: Swissmedic

Study placed in the following topic categories:
Antimetabolites
Allopurinol
Antioxidants
Immunologic Factors
Gastrointestinal Diseases
Thioguanine
Inflammatory Bowel Diseases
Intestinal Diseases
Immunosuppressive Agents
Digestive System Diseases
Azathioprine
Gastroenteritis
Antirheumatic Agents

Additional relevant MeSH terms:
Antimetabolites
Allopurinol
Antimetabolites, Antineoplastic
Antioxidants
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Physiological Effects of Drugs
Inflammatory Bowel Diseases
Enzyme Inhibitors
Intestinal Diseases
Immunosuppressive Agents
Protective Agents
Gout Suppressants
Pharmacologic Actions
Digestive System Diseases
Azathioprine
Therapeutic Uses
Free Radical Scavengers
Gastroenteritis
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 30, 2009