Azathioprine & Allopurinol in Inflammatory Bowel Disease Patients

NCT00849368 | Completed Phase 1 DMC

• 1 other identifier: PHA-08-AZA/ALLO-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics: Quantification of trough concentrations of 6-TGN and 6-MMPN in erythrocytes using HPLC at each dose level.

  three times per cycle

Secondary Outcomes (4)

• 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

Study Arms (1)

Azathioprine / Allopurinol

EXPERIMENTAL

Single arm study: Dose escalations as described.

Drug: Azathioprine / Allopurinol

Interventions

Azathioprine / Allopurinol 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

Also known as: Azathioprine: Imurek (R) 50 mg and 25 mg tablets, Allopurinol: Mephanol (R) 100 mg tablets

Azathioprine / Allopurinol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

Division of Clinical Pharmacology and Toxicology, University Hospital Zurich

Zurich, CH-8091, Switzerland

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

Azathioprine; Allopurinol

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• 01 Studienregister MasterAdmins

  UniversitaetsSpital Zuerich

  STUDY DIRECTOR

• Alexander Jetter, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med.

Study Record Dates

• First Submitted: September 2, 2008
• First Posted: February 23, 2009
• Study Start: January 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: February 7, 2012

Record last verified: 2012-02

Locations

CH (1)