Azathioprine & Allopurinol in Inflammatory Bowel Disease Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alexander Jetter, University of Zurich
ClinicalTrials.gov Identifier:
NCT00849368
First received: September 2, 2008
Last updated: February 6, 2012
Last verified: February 2012

September 2, 2008
February 6, 2012
January 2009
September 2011   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00849368 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Azathioprine & Allopurinol in Inflammatory Bowel Disease Patients
Dose-effect Relationship Between Allopurinol, Azathioprine and 6-thioguanine Nucleotide Levels (6-TGN) in Inflammatory Bowel Disease Patients.

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
Not Provided
Interventional
Phase 1
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Inflammatory Bowel Disease
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
Experimental: Azathioprine / Allopurinol
Single arm study: Dose escalations as described.
Intervention: Drug: Azathioprine / Allopurinol
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
6
September 2011
September 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT00849368
PHA-08-AZA/ALLO-01
Yes
Alexander Jetter, University of Zurich
University of Zurich
Not Provided
Study Director: 01 Studienregister MasterAdmins UniversitaetsSpital Zuerich
Principal Investigator: Alexander Jetter, MD Division of Clinical Pharmacology and Toxicology, University Hospital Zürich, 8091 Zürich, Switzerland
University of Zurich
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP