Crohns DiseasePhase 1NCT00774982
Pilot Comparative Bioavailability Study of 6Mercaptopurine (Delayed Release vs. Purinethol) in Crohns Disease Patients
A Phase 1 study testing Delayed Release 6 mercaptopurine and 6 Mercaptopurine in people with Crohns Disease, run by Teva GTC at 1 site in Israel.
Trial summary
The study is being conducted to evaluate the pharmacokinetic parameters (Cmax, Tmax and AUC) of the new delayed release, lowered dose, 40 mg 6MP test formulation as compared to standard 6MP (100 mg Purinethol) in 12 patients with Crohn's Disease. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Crohns Disease
- What is being tested?
- Delayed Release 6 mercaptopurine and 6 Mercaptopurine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteIsrael
- Study dates
- Dec 2008to Feb 2009
- 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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 12 male and non-pregnant females, aged 18-50 years, with Crohns Disease (CDAI up to 200), non-smoking.
- Crohns Disease diagnosis via colonoscopy with biopsy within the past 12 years No CD medications allowed during study other than 5-ASA and symptomatic relief (anti-diarrheals) Screening lab tests: HGB>= 8.5 g/dl, platelets >= 100,000/mm3, WBC: 3500-12000/mm3, serum albumin above 2.5 g/dl, amylase, lipase and total bilirubin within normal limits; ALT, AST, alkaline phosphatase up to 1.5 x normal limits
Who cannot join
- No more than 2 bowel movements/24 hour period in week prior to screening No patients on methotrexate, cyclosporine, or other anti-TNF alpha, or anti-neoplastics within 3 months of study start NO fistulizing CD or isolated small bowle CD No symptomatic stenosis or ileal strictures,or x-ray evidnece of fibrosed bowel
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot, Randomized, Open-Label, Two-Way Crossover Comparative Bioavailability Study of 40 mg Delayed Release Oral 6Mercaptopurine Versus 100 mg Purinethol in Patients With Crohns Disease
The study is being conducted to evaluate the pharmacokinetic parameters (Cmax, Tmax and AUC) of the new delayed release, lowered dose, 40 mg 6MP test formulation as compared to standard 6MP (100 mg Purinethol) in 12 patients with Crohn's Disease.
The study is being undertaken to prove that the new test formulation is indeed delayed-release and targeted to the ileum, and that the levels of 6MP in the blood following local absorption are lower than that seen following standard Purinethol dosing. This should result in lower, safer mercaptopurine dosing, allowing for uninterrupted treatment with fewer side effects.
Read the detailed description
A new delayed release, faster-disintegrating, lower dose oral formulation of 6 mercaptopurine for targeted delivery to the ileum (the most commonly effected area of Crohns Disease (CD) bowel involvement), was developed and shown to be effective in the three efficacy parameters evaluated in a small group of Crohns Disease patients. Twelve weeks of daily treatment with once-nightly dosing of 40 mg local 6MP resulted in: (1) inducing clinical remission (CDAI scores below 150 as early as weeks 2 and 4), (2) effecting local mucosal healing (as evidenced by lowered CDEIS scores and descriptive conolonoscopy reports) and (3) reducing systemic immunological scores (lowered IFN-gamma Elispot levels).
The current study is being undertaken to confirm, via pharmacokinetic profiles (Cmax, AUC and Tmax), the underlying premises of the above-noted clinical feasibility study. This PK study is being conducted to establish that (1) The delayed release test formulation delivers drug distally to the lower intestine and (2) The delayed release test formulation has the potential for reduced systemic toxicity. The first aspect will be established by comparing the Tmax of the delayed release test formulation vs. oral Purinethol, while the second aspect will be established by comparing the Cmax and AUC of the 40 mg test dose vs. standard 100 mg Purinethol. It is anticipated that the delayed release test formulation will exhibit a later Tmax and reduced Cmax and AUC as compared to reference Purinethol.
Additionally, immunology testing to measure the effect of the new 6MP formulation on immunological FACS analysis will be performed on peripheral blood lymphocytes at 0, 12 and 24 hours post-dosing of each formualtion. Lymphocytes will be tested for surface marker expression (ex: CD3, CD4, CD8, CD25, NKT, etc.), with anticipated results a greater lowering of immune parameters after even 1 dose of 40 mg delayed release test drug, as compared to 100 mg Purinethol.
- Conditions
- Crohns Disease
- Being tested
- Delayed Release 6 mercaptopurine, 6 Mercaptopurine
- Keywords
- Crohns Disease, Pharmacokinetics, Local Targeted Delivery to the Ileum, Delayed Release, Immunology Measurements, Pharmacokinetics in Crohns Disease Patients
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delayed Release 6 mercaptopurineDrug
Also called Administration 1 (A): 1 x 40 mg Delayed Release 6MP TEST
oral tablet, 1 x 40 mg Delayed Release 6MP tablet, single-dose
6 MercaptopurineDrug
Also called Administration 2 (B): 2 x 50 mg Purinethol REFERENCE
Oral Tablet, 2 x 50 mg 6MP Reference, single-dose
| Study group | Role | What they receive |
|---|---|---|
| 1 6MP Test Formulation | Experimental | 1 x 40 mg Oral Tablet, 6 MP Delayed Release Test Formulation, for targeted ileal delivery Receives: Drug: Delayed Release 6 mercaptopurine |
| 2. 6MP Reference Formulation | Active comparator | 2 x 50 mg oral tablet, PURINETHOL Receives: Drug: 6 Mercaptopurine |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK parameters: AUC, Cmax and Tmax
Measured: Following single dose of test or reference drug
Secondary outcomes (1)
FACS analysis of peripheral blood lymphocytes following single dose of test vs. reference formulation
Measured: Comparison of values from blood collected at 0, 12 and 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2008 (estimated)
- Study startDec 2008
- Primary completionFeb 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohns DiseaseStudies of the same condition, open and under way.
- 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva GTC
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Yaron Ilan, MD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00774982
- Sponsor's protocol ID
- C1/13/6MP-02
- Status last verified
- Jul 2009
- First submitted
- 16 Oct 2008
- Last updated
- 17 Jul 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot, Randomized, Open-Label, Two-Way Crossover Comparative Bioavailability Study of 40 mg Delayed Release Oral 6Mercaptopurine Versus 100 mg Purinethol in Patients With Crohns Disease
- ClinicalTrials.gov ID
- NCT00774982
- Acronym / sponsor ID
- C1/13/6MP-02
- Conditions
- Crohns Disease
- Keywords
- Crohns Disease, Pharmacokinetics, Local Targeted Delivery to the Ileum, Delayed Release, Immunology Measurements, Pharmacokinetics in Crohns Disease Patients
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Teva GTCIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 17 Oct 2008 (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.
The study is being conducted to evaluate the pharmacokinetic parameters (Cmax, Tmax and AUC) of the new delayed release, lowered dose, 40 mg 6MP test formulation as compared to standard 6MP (100 mg Purinethol) in 12 patients with Crohn's Disease.
The study is being undertaken to prove that the new test formulation is indeed delayed-release and targeted to the ileum, and that the levels of 6MP in the blood following local absorption are lower than that seen following standard Purinethol dosing. This should result in lower, safer mercaptopurine dosing, allowing for uninterrupted treatment with fewer side effects.
Detailed description
A new delayed release, faster-disintegrating, lower dose oral formulation of 6 mercaptopurine for targeted delivery to the ileum (the most commonly effected area of Crohns Disease (CD) bowel involvement), was developed and shown to be effective in the three efficacy parameters evaluated in a small group of Crohns Disease patients. Twelve weeks of daily treatment with once-nightly dosing of 40 mg local 6MP resulted in: (1) inducing clinical remission (CDAI scores below 150 as early as weeks 2 and 4), (2) effecting local mucosal healing (as evidenced by lowered CDEIS scores and descriptive conolonoscopy reports) and (3) reducing systemic immunological scores (lowered IFN-gamma Elispot levels).
The current study is being undertaken to confirm, via pharmacokinetic profiles (Cmax, AUC and Tmax), the underlying premises of the above-noted clinical feasibility study. This PK study is being conducted to establish that (1) The delayed release test formulation delivers drug distally to the lower intestine and (2) The delayed release test formulation has the potential for reduced systemic toxicity. The first aspect will be established by comparing the Tmax of the delayed release test formulation vs. oral Purinethol, while the second aspect will be established by comparing the Cmax and AUC of the 40 mg test dose vs. standard 100 mg Purinethol. It is anticipated that the delayed release test formulation will exhibit a later Tmax and reduced Cmax and AUC as compared to reference Purinethol.
Additionally, immunology testing to measure the effect of the new 6MP formulation on immunological FACS analysis will be performed on peripheral blood lymphocytes at 0, 12 and 24 hours post-dosing of each formualtion. Lymphocytes will be tested for surface marker expression (ex: CD3, CD4, CD8, CD25, NKT, etc.), with anticipated results a greater lowering of immune parameters after even 1 dose of 40 mg delayed release test drug, as compared to 100 mg Purinethol.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 6MP Test Formulation | Experimental | Drug: Delayed Release 6 mercaptopurine1 x 40 mg Oral Tablet, 6 MP Delayed Release Test Formulation, for targeted ileal delivery |
| 2. 6MP Reference Formulation | Active comparator | Drug: 6 Mercaptopurine2 x 50 mg oral tablet, PURINETHOL |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 12 male and non-pregnant females, aged 18-50 years, with Crohns Disease (CDAI up to 200), non-smoking.
- Crohns Disease diagnosis via colonoscopy with biopsy within the past 12 years No CD medications allowed during study other than 5-ASA and symptomatic relief (anti-diarrheals) Screening lab tests: HGB>= 8.5 g/dl, platelets >= 100,000/mm3, WBC: 3500-12000/mm3, serum albumin above 2.5 g/dl, amylase, lipase and total bilirubin within normal limits; ALT, AST, alkaline phosphatase up to 1.5 x normal limits
Key exclusion criteria (1 listed)
- No more than 2 bowel movements/24 hour period in week prior to screening No patients on methotrexate, cyclosporine, or other anti-TNF alpha, or anti-neoplastics within 3 months of study start NO fistulizing CD or isolated small bowle CD No symptomatic stenosis or ileal strictures,or x-ray evidnece of fibrosed bowel
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 |
|---|---|---|
| Delayed Release 6 mercaptopurineAlso: Administration 1 (A): 1 x 40 mg Delayed Release 6MP TESToral tablet, 1 x 40 mg Delayed Release 6MP tablet, single-dose | Drug | 1 6MP Test Formulation |
| 6 MercaptopurineAlso: Administration 2 (B): 2 x 50 mg Purinethol REFERENCEOral Tablet, 2 x 50 mg 6MP Reference, single-dose | Drug | 2. 6MP Reference Formulation |
Primary outcome
PK parameters: AUC, Cmax and Tmax
Time frame: Following single dose of test or reference drug
1 secondary outcome
FACS analysis of peripheral blood lymphocytes following single dose of test vs. reference formulation
Time frame: Comparison of values from blood collected at 0, 12 and 24 hours post-dose
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 17 Jul 2009.
Related trials for Crohns Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
ALPCO Calprotectin CLIA Assay - Measurement of Calprotectin Levels in Human Stool
Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis), Inflammatory Bowel Syndrome
RecruitingPhase 3
Extension Study of Long-term Safety and Efficacy of Tulisokibart in Participants With Crohn's Disease or Ulcerative Colitis (MK-7240-011)
Crohn Disease, Colitis, Ulcerative
Active, not recruitingPhase 4
Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA) and Diet in Inflammatory Bowel Disease (IBD) Patients
Crohn Disease
RecruitingPhase 2
NOV-ERA - A Clinical Trial to Assess the Efficacy and Safety of Ontunisertib Compared to Placebo in Patients With Fibrostenosing Crohn's Disease
Fibrostenotic Crohn's Disease
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.
Yaron Ilan, MD principal investigator
Hadassah Medical Organization
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 Delayed Release 6 mercaptopurine and 6 Mercaptopurine in people with Crohns Disease, run by Teva GTC at 1 site in Israel.
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 2 inclusion and 1 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 17 Jul 2009. 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 Israel. 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?
PK parameters: AUC, Cmax and Tmax (time frame: Following single dose of test or reference drug). 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 17 Jul 2009.