Trial record 2 of 17 for:    methotrexate and uc

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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
University of Western Ontario, Canada
ClinicalTrials.gov Identifier:
NCT01716039
First received: October 15, 2012
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Ulcerative Colitis
Drug: MTX 12.5
Drug: MTX 25
Drug: Adalimumab
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by University of Western Ontario, Canada:

Primary Outcome Measures:
  • Pharmacokinetic Analysis (PK) will measure antidrug antibodies (ADAs)and plasma concentrations of adalimumab and methotrexate. [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]

    PK parameters will include:

    • Maximum plasma concentration (Cmax)
    • Time to reach Cmax (Tmax)
    • Area under the concentration time curve (AUC)
    • Elimination rate constant (k) Elimination half-life (t1/2)


Secondary Outcome Measures:
  • Clinical and Endoscopic Evaluation of the Efficacy of Combination Therapy [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    The primary efficacy outcome will be assessed by comparing the change in the modified Baron score from baseline to the final visit between the treatment groups

  • Identify covariates [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    To identify covariates (gender, weight, BMI, albumin, TNF, CRP, disease severity, concomitant medications) that might influence the clearance and or disposition of adalimumab

  • Relationship between PK and efficacy [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    To evaluate the relationship between PK and efficacy (PD)


Estimated Enrollment: 100
Study Start Date: June 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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
Drug: MTX 12.5

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

Other Name: MTX
Drug: Adalimumab
Subjects will receive 18 weekly doses of adalimumab
Other Name: Humira
Active Comparator: MTX 25 mg
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

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

Other Name: MTX
Drug: Adalimumab
Subjects will receive 18 weekly doses of adalimumab
Other Name: Humira
Placebo Comparator: Placebo
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
Subjects will receive 18 weekly doses of adalimumab
Other Name: Humira

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01716039

Sponsors and Collaborators
University of Western Ontario, Canada
Abbott
Investigators
Principal Investigator: Brian Feagan, MD Robarts Research Institute - Western University
  More Information

Publications:
Responsible Party: University of Western Ontario, Canada
ClinicalTrials.gov Identifier: NCT01716039     History of Changes
Other Study ID Numbers: RP1204
Study First Received: October 15, 2012
Last Updated: March 19, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of Western Ontario, Canada:
Moderately to severely active Ulcerative Colitis

Additional relevant MeSH terms:
Methotrexate
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on August 28, 2014