Inflammatory Bowel DiseasePhase 1NCT00849368
Azathioprine & Allopurinol in Inflammatory Bowel Disease Patients
A Phase 1 study testing Azathioprine / Allopurinol in people with Inflammatory Bowel Disease, run by University of Zurich at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Inflammatory Bowel Disease
- What is being tested?
- Azathioprine / Allopurinol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2009to Sep 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Division of Clinical Pharmacology and Toxicology, University Hospital Zurich
Zurich, CH-8091
About this study
Official title: 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
- Conditions
- Inflammatory Bowel Disease
- Being tested
- Azathioprine / Allopurinol
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azathioprine / AllopurinolDrug
Also called Azathioprine: Imurek (R) 50 mg and 25 mg tablets, Allopurinol: Mephanol (R) 100 mg tablets
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
| Study group | Role | What they receive |
|---|---|---|
| Azathioprine / Allopurinol | Experimental | Single arm study: Dose escalations as described. Receives: Drug: Azathioprine / Allopurinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics: Quantification of trough concentrations of 6-TGN and 6-MMPN in erythrocytes using HPLC at each dose level.
Measured: 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.
Measured: once per cycle
Efficacy: Change in disease activity score in relationship to the dose level attained.
Measured: once per cycle
TPMT activity assessment
Measured: 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
Measured: screening, up to three times per cycle, follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Bowel DiseaseStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexander Jetter, University of Zurich
- Investigators
- 01 Studienregister MasterAdmins, Study director, UniversitaetsSpital ZuerichAlexander Jetter, MD, Principal investigator, Division of Clinical Pharmacology and Toxicology, University Hospital Zürich, 8091 Zürich, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00849368
- Sponsor's protocol ID
- PHA-08-AZA/ALLO-01
- Status last verified
- Feb 2012
- First submitted
- 2 Sep 2008
- Last updated
- 7 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-effect Relationship Between Allopurinol, Azathioprine and 6-thioguanine Nucleotide Levels (6-TGN) in Inflammatory Bowel Disease Patients.
- ClinicalTrials.gov ID
- NCT00849368
- Acronym / sponsor ID
- PHA-08-AZA/ALLO-01
- Conditions
- Inflammatory Bowel Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 23 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azathioprine / Allopurinol | Experimental | Drug: Azathioprine / AllopurinolSingle arm study: Dose escalations as described. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azathioprine / AllopurinolAlso: Azathioprine: Imurek (R) 50 mg and 25 mg tablets, Allopurinol: Mephanol (R) 100 mg tabletsBoth 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 | Drug | Azathioprine / Allopurinol |
Primary outcome
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
4 secondary outcomes
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
Efficacy: Change in disease activity score in relationship to the dose level attained.
Time frame: once per cycle
TPMT activity assessment
Time frame: 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
Time frame: screening, up to three times per cycle, follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
01 Studienregister MasterAdmins study director
UniversitaetsSpital Zuerich
Alexander Jetter, MD principal investigator
Division of Clinical Pharmacology and Toxicology, University Hospital Zürich, 8091 Zürich, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azathioprine / Allopurinol in people with Inflammatory Bowel Disease, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2012.