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

Phase 2

Terminated

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
MTX 25 mg	MTX 25	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
Placebo	Adalimumab	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
MTX 12.5	MTX 12.5	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
MTX 12.5	Adalimumab	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
MTX 25 mg	Adalimumab	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

Primary Outcome Measures

Name	Time	Method
Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups	Baseline up to Week 18	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

Secondary Outcome Measures

Name	Time	Method
Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.	Baseline up to Week 18	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