Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active ulcerative colitis.

Detailed Description
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Assess the Pharmacokinetic dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active UC.

Official Title
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A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: MTX 12.5
* Drug: MTX 25
* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]). Diagnosis of UC confirmed by established criteria, regardless of disease duration. Moderate to severely active UC, defined by a modified Mayo Score ≥6, with confirmed endoscopic activity by central reader (Mayo endoscopic subscore ≥2). Require initiation with adalimumab for induction of remission. Ability of subject to swallow study drug capsules. Ability of subject to participate fully in all aspects of this clinical trial. Written informed consent must be obtained and documented. Exclusion Criteria: Prior treatment with a TNF antagonist or biological therapy. Prior treatment with MTX. Disease limited to the rectum (proctitis). Documented presence of antibodies against adalimumab. Contraindication for anti-TNF or MTX therapy. Contraindication for endoscopy. Ostomy. Planned surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MTX 12.5<br>Receive once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX and/or placebo in addition to doses of adalimumab | Drug: MTX 12.5<br>* once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or >9). Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab<br>* Other names: MTX;Drug: Adalimumab<br>* Subjects will receive 18 weekly doses of adalimumab<br>* Other names: Humira;|
| Active Comparator: MTX 25 mg<br>Once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX in addition to doses of adalimumab | Drug: MTX 25<br>* once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or >9). Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab<br>* Other names: MTX;Drug: Adalimumab<br>* Subjects will receive 18 weekly doses of adalimumab<br>* Other names: Humira;|
| Placebo Comparator: Placebo<br>Once weekly oral dosing with placebo (n=20) two weeks prior to the initiation of adalimumab. Subjects will receive 18 weekly doses of placebo in addition to doses of adalimumab | Drug: Adalimumab<br>* Subjects will receive 18 weekly doses of adalimumab<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups | The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance | Baseline up to Week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups. | UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration). The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance | Baseline up to Week 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderately to severely active Ulcerative Colitis